THE PATH FORWARD: ADVANCING TREATMENTS AND CURES FOR NEURODEGENERATIVE DISEASES
Summary
Printed record of a hybrid hearing of the Subcommittee on Health of the Committee on Energy and Commerce on July 29, 2021 (Serial No. 117-47), titled "The Path Forward: Advancing Treatments and Cures for Neurodegenerative Diseases", with Chairwoman Anna G. Eshoo presiding. Government witnesses are Richard J. Hodes of the National Institute on Aging, Walter J. Koroshetz of the National Institute of Neurological Disorders and Stroke and Patrizia Cavazzoni of the Food and Drug Administration. Witnesses also include Merit Cudkowicz of Massachusetts General Hospital, Cartier Esham of the Biotechnology Innovation Organization, Jinsy Andrews of Columbia University and Brian Wallach and Sandra Abrevaya of I AM ALS. At the close Ms. Eshoo enters documents from national organizations into the record and gives Members 10 days to submit questions.
Summary drafted by a model from the document's text below and checked by script against that text before publication. It is a navigation aid, not a reading of what the document proves. Where AI is used
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“THE PATH FORWARD: ADVANCING TREATMENTS AND CURES FOR NEURODEGENERATIVE DISEASES.”
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[House Hearing, 117 Congress]
[From the U.S. Government Publishing Office]
THE PATH FORWARD: ADVANCING TREATMENTS
AND CURES FOR NEURODEGENERATIVE DISEASES
=======================================================================
HYBRID HEARING
BEFORE THE
SUBCOMMITTEE ON HEALTH
OF THE
COMMITTEE ON ENERGY AND COMMERCE
HOUSE OF REPRESENTATIVES
ONE HUNDRED SEVENTEENTH CONGRESS
FIRST SESSION
__________
JULY 29, 2021
__________
Serial No. 117-47
[GRAPHIC NOT AVAILABLE IN TIFF FORMAT]
Published for the use of the Committee on Energy and Commerce
govinfo.gov/committee/house-energy
energycommerce.house.gov
______
U.S. GOVERNMENT PUBLISHING OFFICE
52-724 PDF WASHINGTON : 2023
COMMITTEE ON ENERGY AND COMMERCE
FRANK PALLONE, Jr., New Jersey
Chairman
BOBBY L. RUSH, Illinois CATHY McMORRIS RODGERS, Washington
ANNA G. ESHOO, California Ranking Member
DIANA DeGETTE, Colorado FRED UPTON, Michigan
MIKE DOYLE, Pennsylvania MICHAEL C. BURGESS, Texas
JAN SCHAKOWSKY, Illinois STEVE SCALISE, Louisiana
G. K. BUTTERFIELD, North Carolina ROBERT E. LATTA, Ohio
DORIS O. MATSUI, California BRETT GUTHRIE, Kentucky
KATHY CASTOR, Florida DAVID B. McKINLEY, West Virginia
JOHN P. SARBANES, Maryland ADAM KINZINGER, Illinois
JERRY McNERNEY, California H. MORGAN GRIFFITH, Virginia
PETER WELCH, Vermont GUS M. BILIRAKIS, Florida
PAUL TONKO, New York BILL JOHNSON, Ohio
YVETTE D. CLARKE, New York BILLY LONG, Missouri
KURT SCHRADER, Oregon LARRY BUCSHON, Indiana
TONY CARDENAS, California MARKWAYNE MULLIN, Oklahoma
RAUL RUIZ, California RICHARD HUDSON, North Carolina
SCOTT H. PETERS, California TIM WALBERG, Michigan
DEBBIE DINGELL, Michigan EARL L. ``BUDDY'' CARTER, Georgia
MARC A. VEASEY, Texas JEFF DUNCAN, South Carolina
ANN M. KUSTER, New Hampshire GARY J. PALMER, Alabama
ROBIN L. KELLY, Illinois, Vice NEAL P. DUNN, Florida
Chair JOHN R. CURTIS, Utah
NANETTE DIAZ BARRAGAN, California DEBBBIE LESKO, Arizona
A. DONALD McEACHIN, Virginia GREG PENCE, Indiana
LISA BLUNT ROCHESTER, Delaware DAN CRENSHAW, Texas
DARREN SOTO, Florida JOHN JOYCE, Pennsylvania
TOM O'HALLERAN, Arizona KELLY ARMSTRONG, North Dakota
KATHLEEN M. RICE, New York
ANGIE CRAIG, Minnesota
KIM SCHRIER, Washington
LORI TRAHAN, Massachusetts
LIZZIE FLETCHER, Texas
------
Professional Staff
JEFFREY C. CARROLL, Staff Director
TIFFANY GUARASCIO, Deputy Staff Director
NATE HODSON, Minority Staff Director
Subcommittee on Health
ANNA G. ESHOO, California
Chairwoman
G. K. BUTTERFIELD, North Carolina BRETT GUTHRIE, Kentucky
DORIS O. MATSUI, California Ranking Member
KATHY CASTOR, Florida FRED UPTON, Michigan
JOHN P. SARBANES, Maryland, Vice MICHAEL C. BURGESS, Texas
Chair H. MORGAN GRIFFITH, Virginia
PETER WELCH, Vermont GUS M. BILIRAKIS, Florida
KURT SCHRADER, Oregon BILLY LONG, Missouri
TONY CARDENAS, California LARRY BUCSHON, Indiana
RAUL RUIZ, California MARKWAYNE MULLIN, Oklahoma
DEBBIE DINGELL, Michigan RICHARD HUDSON, North Carolina
ANN M. KUSTER, New Hampshire EARL L. ``BUDDY'' CARTER, Georgia
ROBIN L. KELLY, Illinois NEAL P. DUNN, Florida
NANETTE DIAZ BARRAGAN, California JOHN R. CURTIS, Utah
LISA BLUNT ROCHESTER, Delaware DAN CRENSHAW, Texas
ANGIE CRAIG, Minnesota JOHN JOYCE, Pennsylvania
KIM SCHRIER, Washington CATHY McMORRIS RODGERS, Washington
LORI TRAHAN, Massachusetts (ex officio)
LIZZIE FLETCHER, Texas
FRANK PALLONE, Jr., New Jersey (ex
officio)
C O N T E N T S
----------
Page
Hon. Anna G. Eshoo, a Representative in Congress from the State
of California, opening statement............................... 2
Prepared statement........................................... 3
Hon. Brett Guthrie, a Representative in Congress from the
Commonwealth of Kentucky, opening statement.................... 4
Prepared statement........................................... 6
Hon. Frank Pallone, Jr., a Representative in Congress from the
State of New Jersey, opening statement......................... 7
Prepared statement........................................... 8
Hon. Cathy McMorris Rodgers, a Representative in Congress from
the State of Washington, opening statement..................... 9
Prepared statement........................................... 11
Witnesses
Richard J. Hodes, M.D., Director, National Institute on Aging,
National Institutes of Health.................................. 13
Prepared statement \1\
Answers to submitted questions............................... 229
Walter J. Koroshetz, M.D., Director, National Institute of
Neurological Disorders and Stroke, National Institutes of
Health......................................................... 14
Prepared statement \1\....................................... 17
Answers to submitted questions............................... 244
Patrizia Cavazzoni, M.D., Director, Center for Drug Evaluation
and Research, Food and Drug Administration, Department of
Health and Human Services...................................... 30
Prepared statement........................................... 32
Answers to submitted questions \2\
Merit Cudkowicz, M.D., Chair, Department of Neurology, and
Director, Sean M. Healy and AMG Center for ALS, Massachusetts
General Hospital............................................... 79
Prepared statement........................................... 82
Questions submitted for the record \3\....................... 262
Cartier Esham, Ph.D., Chief Scientific Officer, Biotechnology
Innovation Organization........................................ 90
Prepared statement........................................... 92
Answers to submitted questions............................... 269
Jinsy Andrews, M.D., Director of Neuromuscular Clinical Trials,
Columbia University............................................ 97
Prepared statement........................................... 99
Answers to submitted questions............................... 274
Brian Wallach and Sandra Abrevaya, Cofounders, I AM ALS.......... 103
Joint prepared statement..................................... 107
Yvonne Latty, Caregiver.......................................... 113
Prepared statement........................................... 116
Kala Booth, Huntington's Disease Patient and Caregiver........... 121
Prepared statement........................................... 124
----------
\1\ Dr. Hodes and Dr. Koroshetz submitted a joint prepared statement.
\2\ TDr. Cavazzoni's answers to submitted questions have been retained
in committee files and are available at https://docs.house.gov/
meetings/IF/IF14/20210729/113983/HHRG-117-IF14-Wstate-CavazzoniP-
20210729-SD004.pdf.
\3\ Dr. Cudkowicz did not answer submitted questions for the record by
the time of publication.
Submitted Material
Letter of July 28, 2021, from Orly Avitzur, President, American
Academy of Neurology, to Ms. Eshoo and Mr. Guthrie, submitted
by Ms. Eshoo................................................... 158
Statement of Neil Thakur, Chief Mission Officer, The ALS
Association, July 29, 2021, submitted by Ms. Eshoo............. 163
Statement of the Alzheimer's Association and Alzheimer's Impact
Movement, July 29, 2021, submitted by Ms. Eshoo................ 168
Statement of National Neurological Conditions Surveillance
System, Centers for Disease Control and Prevention, July 29,
2021, submitted by Ms. Eshoo................................... 174
Statement of the Neuroscience Working Table, July 29, 2021,
submitted by Ms. Eshoo......................................... 186
Letter of July 24, 2021, from Jamie Rose Caglia Berry to Ms.
Eshoo, submitted by Ms. Eshoo.................................. 190
Statement of Mayuri Saxena, I AM ALS Legislative Affairs
Committee Member, July 26, 2021, submitted by Ms. Eshoo........ 192
Public witness testimony of Christy Alexander, et al., I AM ALS,
submitted by Ms. Eshoo......................................... 196
Statement of the Global Down Syndrome Foundation, July 29, 2021,
submitted by Ms. Eshoo......................................... 215
Statement of Hon. Jeff Fortenberry, a Representative in Congress
from the State of Nebraska, July 29, 2021, submitted by Ms.
Eshoo.......................................................... 217
Letter of July 29, 2021, from the Rare Disease Company Coalition,
to Hon. Patty Murray, Chairwoman, Senate Committee on Heatlh,
Education, Labor, and Pensions, et al., submitted by Ms. Eshoo. 219
Statement of Matthew Rizzo, Chair, American Brain Coalition, July
29, 2021, submitted by Ms. Eshoo............................... 224
THE PATH FORWARD: ADVANCING TREATMENTS
AND CURES FOR NEURODEGENERATIVE DISEASES
----------
THURSDAY, JULY 29, 2021
House of Representatives,
Subcommittee on Health,
Committee on Energy and Commerce,
Washington, DC.
The subcommittee met, pursuant to call, at 11 a.m., in the
John D. Dingell Room 2123, Rayburn House Office Building, and
remotely via Cisco Webex online video conferencing, Hon. Anna
G. Eshoo (Chairwoman of the subcommittee) presiding.
Members present: Representatives Eshoo, Butterfield,
Matsui, Castor, Sarbanes, Welch, Schrader, Cardenas, Ruiz,
Dingell, Kuster, Kelly, Barragan, Blunt Rochester, Craig,
Schrier, Trahan, Pallone (ex officio); Guthrie (subcommittee
ranking member), Upton, Burgess, Griffith, Bilirakis, Bucshon,
Mullin, Hudson, Carter, Dunn, Curtis, Crenshaw, Joyce, and
Rodgers (ex officio).
Also present: Representatives Schakowsky and Lesko.
Staff present: Jeffrey C. Carroll, Staff Director; Waverly
Gordon, General Counsel; Jessica Grandberry, Staff Assistant;
Tiffany Guarascio, Deputy Staff Director; Stephen Holland,
Health Counsel; Zach Kahan, Deputy Director, Outreach and
Member Service; Mackenzie Kuhl, Digital Assistant; Aisling
McDonough, Policy Coordinator; Meghan Mullon, Policy Analyst;
Juan Negrete, Junior Professional Staff Member; Kaitlyn Peel,
Digital Director; Tim Robinson, Chief Counsel; Chloe Rodriguez,
Clerk; Andrew Souvall, Director of Communications, Outreach,
and Member Services; Kimberlee Trzeciak, Chief Health Advisor;
Alec Aramanda, Minority Professional Staff Member, Health;
Sarah Burke, Minority Deputy Staff Director; Theresa Gambo,
Minority Financial and Office Administrator; Seth Gold,
Minority Professional Staff Member, Health; Nate Hodson,
Minority Staff Director; Peter Kielty, Minority General
Counsel; Emily King, Minority Member Services Director; Bijan
Koohmaraie, Minority Chief Counsel, Oversight and
Investigations Chief Counsel; Clare Paoletta, Minority Policy
Analyst, Health; Kristin Seum, Minority Counsel, Health;
Kristen Shatynski, Minority Professional Staff Member, Health;
and Michael Taggart, Minority Policy Director.
Ms. Eshoo. The Subcommittee on Health will now come to
order.
Due to COVID-19, today's hearing is being held remotely, as
well as in person.
For Members and witnesses taking part in person, we are
following the guidance of the CDC and the Office of the
Attending Physician, so please wear your mask when you are not
speaking, and I thank you for doing so.
For Members and witnesses taking part remotely, microphones
will be set on mute to eliminate background noise, and you will
need to unmute your microphone when you wish to speak.
Since Members are participating from different locations at
today's hearing, recognition of Members will be in the order of
subcommittee seniority.
Documents for the record should be sent to Meghan Mullon at
the email address that we have provided to your staff, and all
documents will be entered into the record at the conclusion of
the hearing.
The Chair now recognizes herself for 5 minutes for an
opening statement.
OPENING STATEMENT OF HON. ANNA G. ESHOO, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF CALIFORNIA
My colleagues, I called for today's hearing to discuss the
challenge of advancing treatments and cures for
neurodegenerative diseases. My constituent Jamie Berry was
diagnosed with ALS 1 year ago. She wrote a letter to me saying
that, ``With ALS, a piece of you dies every single day. We are
simply asking for a fighting chance to live the lives we were
meant to live.''
Today we are going to hear from four patients and
caregivers who, like Jamie, are simply asking for a fighting
chance against the neurodegenerative diseases that have
afflicted their families. Brian and Sandra, Kala and Yvonne,
thank you, especially for traveling across the country to offer
your testimony to us. It was a difficult journey that you have
made, and we thank you for being profiles in courage and being
here to offer that testimony.
Our work today is to help create the fighting chance
against these deadly diseases. According to the National
Institute of Neurological Disorders, each year 50 million
Americans are affected by neurological disorders such as ALS,
Alzheimer's, Huntington's disease, and Parkinson's. These
diseases exact an enormous personal toll and a cost to the U.S.
economy as much as $800 billion annually.
Despite the prevalence, the deaths, and the heart-rending
impact on families across our country, there are few effective
treatments for neurological disorders. Lack of investment,
difficult drug approval processes, and limited understanding of
these extremely heterogeneous diseases all keep effective drugs
off the market. Private companies invest one-fourth as much
into neurological drugs as they do for oncology treatments.
Only 7.9 percent of drugs for neurological disorders
successfully make it from phase one to approval. And when they
are successful, neurologic drugs take, on average, 50 percent
longer to reach approval than drugs for other disease areas.
There have been recent breakthroughs in understanding the
genetic basis of the diseases and potential biomarkers, but
this has yet to translate into effective treatments. For
patients, a diagnosis is still a death sentence.
I think every member of our committee has heard from ALS
patients fed up with their lack of options. Two drugs, AMX0035
and NurOwn, have captured attention and sparked a debate over
whether the potential benefits of the drugs outweigh the risks.
Everyone here shares the same goal: full approval for effective
drugs. But the question before us still stands: How do we best
get there?
An obvious first choice is full funding to the FDA to
ensure they are completely staffed and working at capacity. We
made progress with the House fiscal year 2022 appropriations
bill that increases the FDA's budget by nearly $250 million.
But I am still interested in hearing from FDA about what more
should be done to support their important mission.
Second, we need better multidiscipline coordination between
FDA, NIH, academic researchers, private drug companies, and
patients. Breakthroughs in cancer and HIV came from a better
understanding of the basic science of the diseases, but also
through better collaboration, data sharing, and a coordinated
strategy. These efforts will bring the breakthroughs from the
bench to the bedside.
That is why I am pleased to be working with the Biden-
Harris administration to create the Advanced Research Projects
Agency for Health, ARPA-H. This new, independent agency will
take on projects like Alzheimer's and ALS, where the market has
failed to invest, due to risk, and bring new strategies and
collaborations to our current siloed system.
Finally, there needs to be clarity and transparency about
the standards for approval for deadly diseases with unmet
medical needs. A promise of flexibility rings hollow when it is
undefined. I believe these challenges are not insurmountable,
that these diseases are not incurable, and that we can provide,
as my constituent said, a fighting chance for patients to live
the lives they were meant to live.
That is our work today, and for the days and the years
ahead.
[The prepared statement of Ms. Eshoo follows:]
Prepared Statement of Hon. Anna G. Eshoo
I called for today's hearing to discuss the challenge of
advancing treatments and cures for neurodegenerative diseases.
My constituent, Jamie Berry, was diagnosed with ALS one
year ago. She wrote a letter to me saying that ``With ALS, a
piece of you dies every single day. We are simply asking for a
fighting chance to live the lives we were meant to live.''
Today, we will hear from four patients and caregivers who,
like Jamie, are simply asking for a ``fighting chance'' against
the neurodegenerative diseases that have afflicted their
families. Brian and Sandra, Kala and Yvonne, thank you,
especially for traveling across the country, to offer your
testimony to us. It was a difficult journey that you've made
and we thank you for being profiles of courage and being here
to offer that testimony.
Our work today is to help create the fighting chance
against these deadly diseases.
According to the National Institute of Neurological
Disorders, each year 50 million Americans are affected by
neurological disorders such as ALS, Alzheimer's, Huntington's,
and Parkinson's. These diseases exact an enormous personal toll
and cost the U.S. economy as much as $800 billion dollars
annually.
Despite the prevalence, the deaths, and the heartrending
impact on families across the country, there are few effective
treatments for neurological disorders.
Lack of investment, difficult drug approval processes, and
limited understanding of these extremely heterogenous diseases
all keep effective drugs off the market.
Private companies invest one-fourth as much into
neurological drugs as they do for oncology treatments. Only
7.9% of drugs for neurological disorders successfully make it
from Phase 1 to approval. When they are successful, neurologic
drugs take, on average, 57% longer to reach approval than drugs
for other disease areas.
There have been recent breakthroughs in understanding the
genetic basis of the diseases and potential biomarkers, but
this has yet to translate into effective treatments. For
patients, a diagnosis is still a death sentence.
I think every member of our committee has heard from ALS
patients fed up with their lack of options. Two drugs, AMX0035
and NurOwn, have captured attention and sparked a debate over
whether the potential benefits of the drugs outweigh the risks.
Everyone here shares the same goal: Full approval for
effective drugs. But the question before us still stands: How
do we best get there?
An obvious first choice is full funding to the FDA to
ensure they're completely staffed and working at capacity. We
made progress with a House appropriations bill that increases
the FDA's budget by nearly $250 million, but I'm still
interested in hearing from FDA about what more should be done
to support their important mission.
Second, we need better multidiscipline coordination between
FDA, NIH, academic researchers, private drug companies, and
patients. Breakthroughs in cancer and HIV came from a better
understanding of the basic science of the diseases, but also
through better collaboration, data-sharing, and a coordinated
strategy. These efforts will bring the breakthroughs from the
bench to bedside.
That's why I'm pleased to be working with the Biden-Harris
Administration to create the Advanced Research Projects Agency
for Health, ARPA-H. This new, independent agency will take on
projects like Alzheimer's and ALS where the market has failed
to invest due to risk and bring new strategies and
collaborations to our current siloed system.
Finally, there needs to be clarity and transparency about
the standards for approval for deadly diseases with unmet
medical needs. A promise of ``flexibility'' rings hollow when
it is undefined.
These challenges are not insurmountable. These diseases are
not incurable. We can provide, as my constituent said, the
fighting chance for patients to live the lives they were meant
to live.
That's our work today and for the days and years ahead.
Ms. Eshoo. The Chair now is pleased to recognize Mr.
Guthrie, our distinguished ranking member of the Subcommittee
on Health, for 5 minutes for his opening statement.
OPENING STATEMENT OF HON. BRETT GUTHRIE, A REPRESENTATIVE IN
CONGRESS FROM THE COMMONWEALTH OF KENTUCKY
Mr. Guthrie. Thank you, Chair Eshoo, for holding this
important hearing about advancing treatments and cures for
neurodegenerative diseases.
I want to recognize and thank Kala Booth, who is here today
to testify on her experience with Huntington's disease. Kala is
a constituent of mine from Cecilia, Kentucky. When not
advocating for patients with Huntington's disease and their
families, she is--often can be found face painting at community
events. Kelly is the fourth known suspected generation of her--
of HD in her family, and is a strong advocate and voice for the
Huntington's disease community.
We are here today to examine how we can further advance
treatments and hopefully find cures for patients suffering from
neurodegenerative diseases. We have made progress to create an
environment in the United States that encourages innovation for
treatments. Thanks to Representative Upton and Representative
DeGette in this committee, the 21st Century Cures modernized
our healthcare innovation infrastructure and included more
flexibility to capitalize on this exciting time in science and
enable private-sector innovation.
This committee has also worked on reauthorizing the
National Institutes of Health and ensuring its budget is
adequate to foster research for treatments and cures. Congress
has provided FDA the resources and tools to expeditiously
review drugs for serious unmet needs and rare diseases. We have
continued to examine the expanded access pathway to drugs
outside of clinical trials and added a flexible, right-to-try
pathway for patients seeking access to experimental drugs.
While we have come far, we have a long road ahead to help
patients and their families.
One neurodegenerative disease that I have focused on ever
since coming to Congress is Alzheimer's. Alzheimer's is the
sixth-leading cause of death in the United States. In 2021, an
estimated 6.2 million Americans aged 65 and older are living
with Alzheimer's. By 2060, that number is expected to reach
13.8 million, barring the development of a medical breakthrough
to prevent, slow, or decrease the disease.
My bill, the Bold Infrastructure for Alzheimer's Act, was
signed into law in 2018, which created a public health
infrastructure across the country to support prevention,
treatment, and care for Alzheimer's patients and related
neurodegenerative diseases. I have continued my commitment to
this issue by introducing the Comprehensive Care for
Alzheimer's Act this Congress. This bill works to reduce
medical complications for these patients by creating a new way
to fund dementia through Medicare.
It is not just Alzheimer's disease but the other
neurodegenerative diseases that are devastating for the person
who suffers with the disease and their family, friends, and
loved ones. Huntington's disease is a progressive brain
disorder caused by an inherited gene, and can appear as early
as age 2 or as late as 80 years old. More than 200,000
Americans are at risk of inheriting the gene from a parent with
HD.
Parkinson's disease is another of the progressive brain
disorders that affects approximately 60,000 Americans each
year. An estimated 50 to 80 percent of individuals with
Parkinson's disease may experience dementia in their lifetime.
ALS, referred to as Lou Gehrig's disease, is a progressive
nervous system that affects vital nerve cells in the brain and
spinal cord. For people with ALS, the average survival time is
3 years, and reports suggest 15,000 Americans have ALS.
Well, I think we can all agree, while we want to advance
treatment for cures for all neurodegenerative diseases, let me
point out that H.R. 3, the drug pricing bill, is not the path
forward. If this bill becomes law, I believe innovation for
therapies to treat neurodegenerative diseases will be in
jeopardy or quite possibly decimated altogether. We have seen
estimates that 15 drugs over 10 years, or as many as 100
lifesaving drugs, would not come to market due to H.R. 3,
because it disincentivizes research and development. H.R. 3
would directly hurt patients like the ones before us today.
I support the bipartisan alternative, Lower Cost and More
Cures Act, to reduce drug prices and protect innovative cures.
I am glad to have Kala with us today. Also, we have Brian
Wallach and Yvonne Latty here with us today to share how
Congress can keep hope alive, and promote innovation for
lifesaving cures.
I look forward to working on a solution for American
patients. I look forward to working with the chair, and I look
forward to seeing a better future, where people can live the
life that they were meant to live.
[The prepared statement of Mr. Guthrie follows:]
Prepared Statement of Hon. Brett Guthrie
Thank you, Chair Eshoo, for holding this important hearing
about advancing treatments and cures for neurodegenerative
diseases.
I want to recognize and thank Kala Booth, who is here today
to testify on her experience with Huntington's disease. Kala is
a constituent of mine from Cecilia, Kentucky. While not
advocating for patients with Huntington's disease and their
families, she can often be found face painting at community
events. Kala, is the fourth known suspected generation of HD in
her family and is a strong advocate and voice for the
Huntington's disease community.
We are here today to examine how we can further advance
treatments and hopefully soon, find cures for patients
suffering from the more than 600 known neurological diseases.
We have made progress to create an environment in the
United States that encourages innovation for new treatments.
Thanks to Rep. Upton, Rep. DeGette, and this committee, 21st
Century Cures modernized our health care innovation
infrastructure and included more flexibility to capitalize on
this exciting time in science and enable private sector
innovation. This committee has also worked on reauthorizing the
National Institutes of Health's and ensuring its budget is
adequate to help foster research for new treatments and cures.
Congress has provided FDA the resources and tools to
expeditiously review drugs for serious, unmet needs and rare
diseases. We have continued to examine the expanded access
pathway to drugs outside of clinical trials, and added a
flexible ``right to try'' pathway for patients seeking access
to experimental drugs. While we have come far, we still have a
long road ahead to help patients and their families.
One neurodegenerative disease that I have focused on ever
since coming to Congress is Alzheimer's.
Alzheimer's is the sixth leading cause of death in the
United States. In 2021, an estimated 6.2 million Americans age
65 and older are living with Alzheimer's. By 2060, that number
is expected to reach 13.8 million barring the development of
medical breakthroughs to prevent, slow, or cure the disease.
My bill, the BOLD Infrastructure for Alzheimer's Act, was
signed into law in 2018, which created a public health
infrastructure across the country to support prevention,
treatment, and care for patients with Alzheimer's and related
neurological diseases.
I have continued my commitment to this issue by introducing
the Comprehensive Care for Alzheimer's Act this Congress. This
bill would reduce medical complications for these patients by
creating a new way to fund dementia care through Medicare.
It's not just Alzheimer's disease, but also other
neurological diseases that are devastating for the person who
suffers with the disease and their family, friends, and loved
ones.
Huntington's disease (HD) is a progressive brain disorder
caused by an inherited gene and can appear as early as age 2 or
as late as 80 years old. More than 200,000 Americans are at-
risk of inheriting the gene from a parent with HD.
Parkinson's disease is another type of progressive brain
disorder that affects approximately 60,000 Americans each year.
An estimated 50-80% of individuals with Parkinson's disease may
experience dementia in their lifetime.
ALS, often referred to as Lou Gehrig's disease, is a
progressive nervous system disease that affects vital nerve
cells in the brain and spinal cord. For people with ALS, the
average survival time is three years and reports suggest 15,000
Americans have ALS.
While I think we can all agree we want to advance treatment
and cures for all neurodegenerative diseases, H.R. 3, Speaker
Pelosi's drug pricing bill is NOT the path forward.
If this partisan bill becomes law, I believe innovation for
therapies to treat neurological diseases will come to a full
stop. We've seen estimates that 15 drugs over 10 years or as
many as 100 life-saving drugs would not come to market due to
H.R. 3 because it disincentivizes research and development.
H.R. 3 would directly hurt the patients before us today. I
support the bipartisan alternative, the Lower Costs, More Cures
Act, to reduce drug prices and also protect innovation for
cures.
I'm glad we have Kala, Brian Wallach, and Yvonne Larry here
with us today to share how Congress can keep hope alive and
promote innovation for life-saving cures. I look forward to
working on solutions for American patients and their families
I yield back.
Mr. Guthrie. I yield back.
Ms. Eshoo. The gentleman yields back, and the Chair thanks
him for his opening statement.
And the Chair is pleased to now recognize the chairman of
the full committee, Mr. Pallone, for his 5 minutes for an
opening statement.
OPENING STATEMENT OF HON. FRANK PALLONE, Jr., A REPRESENTATIVE
IN CONGRESS FROM THE STATE OF NEW JERSEY
Mr. Pallone. Thank you, Chairwoman Eshoo.
Our understanding of the human brain has rapidly increased
in recent years, thanks to advancements in science and
research. Yet neurodegenerative diseases and their causes
continue to be a mystery in many ways. Few treatments for the
symptoms of neurodegenerative diseases exist, and there are
also no known cures that significantly slow or eliminate
disease progression. As a result, millions of Americans and
their families face the heartbreaking daily challenges that
come with a neurodegenerative disease.
Congress and this committee in recent years have supported
substantial investments in neurodegenerative disease research,
and flexibilities for clinical research. In 2016 we passed the
21st Century Cures Act, which authorized over $1.5 billion to
support the National Institutes of Health's Brain Research
through Advancing Innovative Neurotechnologies, or BRAIN,
Initiative. This initiative's mission is to revolutionize our
understanding of the human brain, and discover new ways to
treat, cure, and prevent brain disorders, including
neurodegenerative diseases.
By accelerating the development of novel technologies to
map a new picture and understanding of the brain, the BRAIN
Initiative is providing a revolutionary foundation for future
research and clinical development. And this work will be
augmented by the Advanced Research Projects Agency for Health,
or ARPA-H, proposed by President Biden.
The FDA also plays a key role. The agency is responsible
for the safety and efficacy of all drugs and treatments and
development, including those to treat brain disorders. FDA also
provides guidance to industry on clinical trial design,
meaningful endpoint considerations to determine whether a
treatment is beneficial, and market approval. It also works
with physicians and patients when treatment options may be
unavailable.
Through both the 21st Century Cures and the FDA
Reauthorization Act, this committee has encouraged greater
guidance on the use of novel clinical trials, and the inclusion
of patients in the drug development process. These are all
promising steps, but it is clear that a lot more must be done
to support the discovery and development of safe and effective
treatments and cures, and to provide quality, affordable, and
equitable care to patients and their families.
In order to protect patients, caretakers, and the American
public, it is important that we understand the current state of
science for neurodegenerative diseases and how we can further
improve access to clinical trials and the development of
potential treatments or cures. And it is our responsibility to
provide Federal agencies with the necessary resources.
So we have two panels. On our first panel we will hear from
government representatives at the FDA, the National Institutes
on Aging, and the National Institutes of Neurological Disorders
and Stroke. And I am particularly interested in hearing about
the progress that has been made since the passage of both the
21st Century Cures Act and the FDA Reauthorization Act in 2017
and how these programs are affecting clinical research and drug
development, and what more needs to be done.
On our second panel we will hear from researchers,
industry, patients, and caretakers, and their experiences are
critical to our work here today. Patients and their caretakers
live the physical and emotional symptoms of these diseases
every day, including the arduous process of enrolling and
participating in a clinical trial and searching for available
treatments. These are our neighbors and friends, and for many
of us, our family.
So I also look forward to hearing from those on the cutting
edge of research into ALS and neurodegenerative diseases who
have conducted clinical trials and treated patients with the
disease.
We will also hear from industry about therapies in the
pipeline, and the challenges manufacturers face in developing
treatments for neurodegenerative diseases.
I thank all the witnesses for appearing here today. Thank
you, Madam Chair, for your role in making sure that we have
this hearing today, and I yield back the balance of my time.
[The prepared statement of Mr. Pallone follows:]
Prepared Statement of Hon. Frank Pallone, Jr.
Our understanding of the human brain has rapidly increased
in recent years thanks to advancements in science and research.
Yet neurodegenerative diseases and their causes continue to be
a mystery in many ways. Few treatments for the symptoms of
neurodegenerative diseases exist, and there are no known cures
that significantly slow or eliminate disease progression. As a
result, millions of Americans and their families face the
heartbreaking daily challenges that come with a
neurodegenerative disease.
Congress and this committee in recent years have supported
substantial investments in neurodegenerative disease research
and flexibilities for clinical research.
In 2016, we passed the 21st Century Cures Act, which
authorized over $1.5 billion to support the National Institutes
of Health's (NIH) Brain Research through Advancing Innovative
Neurotechnologies (BRAIN) Initiative or the BRAIN Initiative.
This Initiative's mission is to revolutionize our understanding
of the human brain and discover new ways to treat, cure, and
prevent brain disorders, including neurodegenerative diseases.
By accelerating the development of novel technologies to map a
new picture and understanding of the brain, the BRAIN
Initiative is providing a revolutionary foundation for future
research and clinical development. This work will be augmented
by the Advanced Research Projects Agency for Health, or ARPA-H,
proposed by President Biden.
The Food and Drug Administration (FDA) also plays a key
role. The agency is responsible for the safety and efficacy of
all drugs and treatments in development, including those to
treat brain disorders. FDA also provides guidance to industry
on clinical trial design, meaningful endpoint considerations to
determine whether a treatment is beneficial, and market
approval. It also works with physicians and patients when
treatment options may be unavailable.
Through both 21st Century Cures and the FDA Reauthorization
Act, this committee has encouraged greater guidance on the use
of novel clinical trials and the inclusion of patients in the
drug development process.
These are all promising steps, but it is clear that more
must be done to support the discovery and development of safe
and effective treatments and cures, and to provide quality,
affordable, and equitable care to patients and their families.
In order to protect patients, caretakers, and the American
public, it is important that we understand the current state of
science for neurodegenerative diseases and how we can further
improve access to clinical trials and the development of
potential treatments or cures.
It is our responsibility to provide Federal agencies with
the necessary resources.
On our first panel, we will hear from government
representatives at the FDA, National Institute on Aging, and
National Institutes of Neurological Disorders and Stroke. I am
particularly interested in hearing about the progress that has
been made since the passage of both the 21st Century Cures Act
and the FDA Reauthorization Act in 2017, how these programs are
affecting clinical research and drug development, and what more
needs to be done.
On our second panel, we will hear from researchers,
industry, patients, and caretakers. Their experiences are
critical to our work here today.
Patients and their caretakers live the physical and
emotional symptoms of these diseases every day, including the
arduous process of enrolling and participating in a clinical
trial and searching for available treatments. These are our
neighbors, friends, and for many of us, family.
I also look forward to hearing from those on the cutting
edge of research into ALS and neurodegenerative diseases, who
have conducted clinical trials and treated patients with the
disease. We will also hear from industry about therapies in the
pipeline and the challenges manufacturers face in developing
treatments for neurodegenerative diseases.
I thank all of the witnesses for appearing here today, and
I yield back the balance of my time.
Ms. Eshoo. The gentleman yields back. The Chair now
recognizes Representative Cathy McMorris Rodgers, the ranking
member of the full committee.
Good morning to you. You are recognized for your 5 minutes
for an opening statement.
OPENING STATEMENT OF HON. CATHY McMORRIS RODGERS, A
REPRESENTATIVE IN CONGRESS FROM THE STATE OF WASHINGTON
Mrs. Rodgers. Thank you, Madam Chair. Good morning,
everyone.
I was thinking this morning of our work before the
pandemic, the many meetings we have all had to listen to
advocates fighting for cures and treatments. Hundreds of
disease and rare disease groups came to the people's house for
the opportunity to share their stories, advocates like my
friend from Spokane, Gail Gleason, Steve Gleason's mom. They,
like millions of other people, have an extraordinary amount of
hope in the promise of American innovation.
Whether it is ALS, Alzheimer's, Huntington's, or another
disease, the hope for lifesaving treatments and cures is here,
in the United States of America. We cannot forget that. We have
led the world. The United States of America is where hope
becomes a reality.
That brings me to H.R. 3, Speaker Pelosi's harmful
government price controls for prescription drugs. As one mom
told this subcommittee, research will stall under H.R. 3. She
said other countries have price controls and ``innovation
deserts, and innovation deserts are relentless when you need
access to a rare disease treatment to save your children.''
Her son's name is Hunter. He has spinal muscular atrophy,
and he is alive today--in fact, it is his birthday, his 10th
birthday--because of a breakthrough treatment. For children
like Hunter, it would be devastating if price controls were
jammed in the majority's reckless tax and spending. It would
lead to less innovation, fewer cures, and no hope for many
people who deserve a fighting chance for life. For that
fighting chance, we should be working on bipartisan solutions
like H.R. 19, the Lower Cost and More Cures Act.
In addition, we should be leading the way in a bipartisan
way to fund more basic research, support research around the
causes of diseases, and unleash the private sector, just like
we did with COVID-19 vaccines.
This is very personal for me. My son, Cole, has Down
syndrome. It is the most common chromosomal abnormality. Yet
there is still a lot that we don't know about that twenty-first
chromosome. For example, the scientific community has
acknowledged that 100 percent of people with Down syndrome will
develop the brain pathology for Alzheimer's in their lifetime,
but only about half will experience the symptoms of dementia.
The reason for this is still not understood.
Imagine what it would mean if we unlocked the mysteries of
the twenty-first chromosome. It would lead to major medical
discoveries, maybe even a cure for a disease like Alzheimer's.
It is why I was surprised to see the Biden budget proposed to
move NIH's INCLUDE program from the Office of the Director to
the National Institute of Child Health and Human Development
without any explanation.
What problem does this reorganization solve? We will have
the same cross-institute center collaboration and coordination.
This program has been one of my top priorities, and I am
disappointed that, if there were concerns, NIH didn't consult
with Congress.
I want to be very clear. I have historically been a
champion for NIH. I have supported doubling their funding. I
cochair the Neuroscience Caucus. And I have promoted the BRAIN
Initiative from the beginning. That NIH is on the verge of a
trust crisis with this committee and the American people, this
is a warning. Proposing moving a program like INCLUDE with no
consultation with the authorizing committee in Congress is one
thing. Another is a lack of respect for congressional oversight
on how NIH money, research money, is received and spent.
To inform a scientific and objective investigation into the
origins of COVID-19, I have made many requests to NIH to be
transparent and provide documents. We have received no
documents, including for grant documents releasable to the
general public under Federal law. It is unacceptable. I have
told Dr. Collins this directly, when we spoke about ARPA-H.
President Biden has requested more than $6 billion for
ARPA-H, with less accountability and transparency than we have
now. If I were to support this, I would need more confidence
and trust in the oversight and management of the 44 billion in
taxpayer funding going to NIH now, including a clear picture of
how much of that research is going to China.
I will close by thanking the patients, the families, the
caregivers, and the researchers that are with us today. We are
grateful, and we share your mission to unleash American
innovation, support clinical trials, improve early diagnosis,
and improve the lives of millions of Americans. That is why I
am passionate about making sure NIH research dollars are spent
wisely and accountable. That is what we can do, and help
unleash--we need to unleash the private sector also to tackle
these diseases, with the same sense of urgency as we had with
COVID-19.
[The prepared statement of Mrs. Rodgers follows:]
Prepared Statement of Hon. Cathy McMorris Rodgers
INTRO
Thank you, Madam Chair.
I was thinking this morning of our work before the pandemic
...
... and the many meetings we've all had to listen to
advocates fighting for cures and treatments.
Hundreds of disease and rare disease groups came to the
People's House for the opportunity to share their stories with
us.
Advocates like my friend from Spokane, Gail Gleason ...
Steve Gleason's mom.
They--like millions of other people--have an extraordinary
amount of hope in the promise of American innovation.
Whether it's ALS, Alzheimer's, Huntington's, or another
disease ...
... the hope for lifesaving treatments and cures is here
... in America.
We cannot forget that. We have led the world.
America is where hope becomes a reality.
H.R. 3
That brings me to H.R. 3, Speaker Pelosi's radical
government price controls for prescription drugs.
As one mom told this subcommittee, research will stall
under H.R. 3.
She said countries with prices controls are, quote,
``innovation deserts'' and ``innovation deserts are relentless
when you need access to a rare disease treatment to save your
children.''
Her son's name is Hunter. He has spinal muscular atrophy
and he is alive today because of a breakthrough treatment.
For children like Hunter ... it would be devastating if
socialist price controls were jammed in the Democrats' reckless
tax and spending spree.
It would lead to less innovation, fewer cures, and no hope
for many people who deserve a fighting chance at life.
For that fighting chance, we should be working on
bipartisan solutions like H.R. 19, the Lower Costs, More Cures
Act.
Down syndrome
In addition, we should be leading in a bipartisan way to
fund more basic research ...
... support research around the causes of diseases...
... and unleash the private sector just like we did for the
COVID-19 vaccines.
This is very personal for me.
My son Cole has Down syndrome.
It's the most common chromosomal abnormality, yet there's
still a lot we don't know about it and the extra 21st
chromosome.
For example, the scientific community has acknowledged that
100 percent of people with Down syndrome will develop the brain
pathology of Alzheimer's in their lifetime.
But, about only half will experience symptoms of dementia.
The reason for this is still not understood.
Imagine what it would mean if we unlocked the mysteries of
the 21st chromosome?
It could lead to major medical discoveries--maybe even a
cure for a disease like Alzheimer's.
That's why I was surprised to see the Biden budget propose
to move the NIH's INCLUDE program from the Office of the
Director to the National Institute of Child Health and Human
Development, without any explanation. What problem does this
reorganization solve, and will the same cross institute center
collaboration and coordination continue?
This program has been one of my top priorities, and I am
disappointed that, if there were concerns with it, NIH didn't
consult with Congress.
NIH
I want to be very clear. I have historically been a
champion for NIH.
But the NIH is on the verge of a trust crisis with this
committee and the American people.
This is a warning.
Proposing moving a program like INCLUDE with no
consultation with authorizing committees in Congress is one
thing.
Another is the lack of respect for congressional oversight
for how NIH research money is received and spent.
To inform a scientific and objective investigation into the
origins of COVID-19, I have made many requests to the NIH
public servants to be transparent and provide documents.
We have received no documents, including for grant
documents releasable to the general public under Federal law.
This is unacceptable. I've told Dr. Collins this directly
when we spoke about ARPA-H.
President Biden has requested more than $6 billion dollars
for ARPA-H with even less accountability and transparency than
what we have now.
If I were to support this, I need more confidence and trust
in the oversight and management of the $44 billion in taxpayer
funding going to NIH now ... including a clear picture on how
much of that goes toward research in China.
CONCLUSION
I'll close by thanking our patients, families, caregivers,
and researchers with us today.
I'm grateful that you are here.
I share in your mission to unleash American innovation,
support clinical trials, and improve early diagnosis.
It's why I'm passionate about making sure NIH research
dollars are spent wisely and with accountability ...
... and that we do all we can to enable the private sector
to tackle diseases we are discussing today with the same sense
of urgency we had with COVID-19.
I yield back.
Mrs. Rodgers. I yield back.
Ms. Eshoo. The gentlewoman yields back.
The Chair would like to remind Members that, pursuant to
committee rules, all opening statements shall be made part of
the record.
I would now like to introduce our witnesses for our first
panel. And colleagues, we have terrific witnesses today. And I
thank, of course, the minority for your role in bringing people
forward, as well.
First, Dr. Richard Hodes is the director of the National
Institute on Aging at the National Institute of Health.
Welcome to you, Dr. Hodes.
Dr. Walter Koroshetz is the Director of the National
Institute of Neurological Disorders and Stroke at NIH.
Welcome to you, and I hope I haven't butchered your name.
Dr. Patrizia Cavazzoni is the Director of the Center for
Drug Evaluation Research at the U.S. Food and Drug
Administration.
And welcome to you, Dr. Cavazzoni. I think this is--welcome
to the committee. I think it is the first time that you are
testifying here.
So the Chair now recognizes Dr. Hodes for your 5 minutes
for testimony.
STATEMENT OF RICHARD J. HODES, M.D., DIRECTOR, NATIONAL
INSTITUTE ON AGING, NATIONAL INSTITUTES OF HEALTH; WALTER J.
KOROSHETZ, M.D., DIRECTOR, NATIONAL INSTITUTE OF NEUROLOGICAL
DISORDERS AND STROKE, NATIONAL INSTITUTES OF HEALTH; AND
PATRIZIA CAVAZZONI, M.D., DIRECTOR, CENTER FOR DRUG EVALUATION
AND RESEARCH, FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF
HEALTH AND HUMAN SERVICES
STATEMENT OF RICHARD J. HODES, M.D.
Dr. Hodes. Good morning, Chair Eshoo and Ranking Member
Guthrie, and members of the committee. Thank you for the
opportunity to be here. I am Richard Hodes, the Director of the
National Institute on Aging, which aids Federal efforts to
identify ways to prevent, treat, and care for those who are
currently afflicted with Alzheimer's disease.
As noted, Alzheimer's disease is one of the most common and
tragic of the neurodegenerative diseases affecting some 6
million people now, and as noted, again, expected to double, if
nothing changes, by 2050 or 2060.
Thanks to the investment that has come from congressional
appropriations over the past years, we have made enormous
progress in understanding this disease. This understanding has
ranged from basic fundamental science through the translational
trajectory. It has demonstrated the complexity of disease and
given us new insights into potential targets.
From the most basic level of cellular and molecular
biology, enterprises such as the AMP AD, or Accelerating
Medicines Partnership for Alzheimer's. I brought together
pharmaceutical, corporate, fundamental basic science supported
by NIH, as well as philanthropic and foundational funds, all to
generate, in the spirit of open science and acceleration, a
process that has leaded to the identification of some hundreds
of new novel targets for Alzheimer's, the changes that occur in
the brain that represent potential targets for intervention.
The second phase of this, just announced this year, will
move towards the important note of personalized or individual
medicine, which recognizes what we have discovered to be the
complexity and difference in Alzheimer's disease's underlying
process from person to person.
Translating this basic science into clinical interventions
has been identified as a particular challenge. And here, too,
NIH has instituted infrastructure to try to accelerate and de-
risk for public and private sectors the transition from basic
science to clinical studies.
We now support, by NIA alone, more than 50 drug trials that
are targeting a variety of processes, including inflammation, a
protein folding stability, as well as amyloid and tau. These
are moving to recognize the complexity of disease and
understanding that it is unlikely that any one treatment is
going to be sufficient to address all.
We are also looking at the science of clinical research
itself and, as noted, the importance of recruiting a diverse
population represented within the U.S., and including some of
those most vulnerable, such as, as noted, again, Down syndrome.
We have come to realize that the neurodegenerative diseases
like Alzheimer's actually reflect a process that goes on for
years and decades prior to the appearance of symptoms. And
therefore, the importance of being able to identify and
intervene in these processes before massive loss of brain cells
and their connections.
Until recently, Alzheimer's was diagnosed only at post
mortem, or autopsy. Now biomarkers such as PET scans have
allowed us to see the processes that go on in the brain earlier
than symptoms appear and could track the response to
interventions. Most recently, blood markers, which have the
promise of being less intrusive, less invasive, and less
expensive, will bring a new ability to recruit people into
studies, track their disease, and track the outcomes of
intervention.
For people currently living with Alzheimer's disease, it is
also important that research be conducted as NIA makes it a
priority to understand the best ways to support those living
with and those caring for people with Alzheimer's disease. A
collaboratory recently established has now identified an
infrastructure through collaborations and partnerships with
healthcare components that allow us now to conduct pragmatic
trials, in short notice and short turnaround, to identify
success early, for the best ways to care for people with
Alzheimer's, improving quality of life for both them and those
who care for them.
We understand that prevention is also an important way, in
addition to treatments and the arrest of disease, once
identified. And most recently, in terms of preventive
interventions, we have promising news from the study SPRINT
MIND, which showed that a very intensive approach to
controlling blood pressure has the ability to decrease the
appearance of mild cognitive impairment, a kind of precursor of
dementia.
Similarly, we currently are pursuing interventions that
affect diet, exercise, cognitive training, combinations of
them, all in attempt to find ways in which we can intervene to
prevent disease, and the science of behavior change itself, to
make sure that we know how to best inform people so they can
modify their lifestyles in concert with those discoveries.
So, again, I thank you for the ability to appear here, and
thank you profoundly for the support that Congress has given
that has allowed this progress across the----
[Audio malfunction.]
Dr. Hodes [continuing]. As we come to understand
Alzheimer's disease and, therefore--to better intervene. Thank
you so much.
[The joint prepared statement of Dr. Hodes and Dr.
Koroshetz appears after Dr. Koroshetz's spoken remarks]
Ms. Eshoo. Thank you, Dr. Hodes.
Next we call on Dr. Walter Koroshetz for your 5 minutes of
testimony. And thank you for your work and for being here with
us today.
STATEMENT OF WALTER J. KOROSHETZ, M.D.
Dr. Koroshetz. Well, thank you, Chair Eshoo, Ranking Member
Guthrie, and distinguished members of the committee. So, yes, I
am Walter Koroshetz, I am a neurologist currently leading the
National Institute of Neurological Disorders and Stroke, or
NINDS, where we strive to understand the nervous system, its
hundreds of disorders, and to use that knowledge to reduce the
burden of illness.
In neurodegenerative disorders, the nerve cells in the
brain and the spinal cord die over time. And unfortunately,
once a neuron dies, it is not replaced. So there are many forms
of neurodegenerative diseases, each affecting different parts
of the brain or spinal cord. They all rob individuals of the
ability to move or think or communicate, and eventually even to
take care of themselves. And most tragically, they rob people
of years of life.
This motivates the tremendous urgency among the NINDS
research community to uncover highly effective treatments. I am
hopeful that a host of new discoveries and tools will lead to
real breakthroughs, but I am going to focus my remarks on just
three.
The first is genomic therapy. As Congresswoman McMorris
Rodgers just mentioned, recently we saw an almost miraculous
effect of genomic therapies in spinal muscular atrophy. It is a
genetic disease that causes degeneration of the same motor
neurons that are affected by ALS. But gene treatment in infants
has restored function and saved lives. But this is not a one-
off. This success should drive a whole new genomic approach to
the inherited neurological diseases. Genomic therapies are
already underway for Huntington's disease and some forms of
ALS, and I believe that we are on the doorstep of a
revolutionary era of neurogenomic therapies, especially as they
become linked to the cell-specific delivery tools being
developed by the BRAIN Initiative.
Secondly, these genomic tools are now in the clinic for
inherited neurodegenerative disorders, but their promise is
much broader. In most neurodegenerative disorders there is a
subgroup of patients who have an inherited form, due to a known
mutation. But most persons have what is called a sporadic form,
which is not inherited. Luckily, fruitful studies of the
inherited disease-causing mutations have uncovered pathways of
neurodegeneration that are common to the noninherited forms as
well. So therapies are now being developed to manipulate these
common pathways to prevent neuron dysfunction and death.
Thirdly, there has emerged a somewhat common theme in the
treatment--potential treatment of multiple neurodegenerative
disorders. When we look under the microscope at the brains of
people who died from neurodegenerative disorders, we almost
always see clumps of a protein inside the sick or the dying
cells. The specific protein in the brain areas involved vary,
disease to disease. These abnormally aggregated proteins seem
to have the ability to spread from a sick nerve cell to a
healthy one and thereby damage one brain region after another.
As an example, in Parkinson's disease there is some
evidence that protein aggregation may actually start in the
nerves that supply the gut, due to interactions with bacteria
in our guts. Over the course of years, these aggregated
proteins spread from the nerves of the gut, first to the lower
part of the brain and then higher up to cause Parkinsonism.
Treatments to block the spread of aggregative proteins are
being developed for Parkinson's, but for many other
neurodegenerative disorders.
And furthermore, new biomarkers will allow the
identification of at-risk individuals and enable early
treatment that blocks the spread before the disease leads to
any disability whatsoever.
So, very exciting things in these three specific examples,
but let me turn to NINDS's overall strategy for fighting
neurodegenerative diseases.
On the basic science side, we apply what is learned in one
disorder or area of science to others. We place great emphasis
on the nervous system as a whole, coordinating a network of
cells and how it integrates with other body systems. For
instance, elderly persons with a diagnosis of dementia commonly
have signs of Alzheimer's disease along with diseased brain
blood vessels caused by years of high blood pressure and
evidence of injury to the brain's connecting fibers, or so-
called white matter disease.
As Dr. Hodes mentioned, the NIH SPRINT MIND study showed
that aggressive blood pressure control reduces cognitive
impairment over time and suggests that, from what we know now
in how to control blood pressure, we can decrease not only
heart attack and stroke but also cognitive decline and,
potentially, dementia.
And our public health campaign called Mind Your Risks, we
are targeting Black Americans in their late to--20s to mid-40s,
as this group suffers from the greatest disparities in brain
health due to hypertension.
In summary, I would emphasize the tremendous scientific
challenges that remain as we strive to save persons from
neurodegenerative disorders but offer my optimism, which stems
from seeing the emergence of really powerful new tools, just in
the last 5 to 10 years, to be able to combat these diseases.
Thank you very much.
[The joint prepared statement of Dr. Hodes and Dr.
Koroshetz follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Ms. Eshoo. Thank you, Doctor. That is compelling testimony,
and we so appreciate your work and your being with us today.
Next we have Dr. Patrizia Cavazzoni.
Welcome to the committee, and the Chair recognizes you for
your 5 minutes of--to present your testimony to us today.
[Pause.]
Ms. Eshoo. Do we know why Dr. Cavazzoni is not on the
screen?
What?
Voice. Ask her to unmute.
Ms. Eshoo. You need to unmute, Doctor.
Dr. Cavazzoni. My apologies, we were double-muted. Chair
Eshoo----
Ms. Eshoo. Welcome to you. There you are, there you are.
Dr. Cavazzoni. Thank you, here I am. Thank you. Apologies
for the technical difficulties. So let me start.
STATEMENT OF PATRIZIA CAVAZZONI, M.D.
Chair Eshoo, Ranking Member Guthrie, and members of the
committee, thank you for the opportunity to testify before you
today.
Also, I would like to thank my colleagues from NIH for
their ongoing support and willingness to collaborate with FDA
as we translate research into therapies.
In recent years, drug development advancements have been
life-changing. New therapies are brought to patients faster,
thanks to more efficient clinical trials and the use of
expedited regulatory pathways. One need only look at the pace
of development of the COVID vaccines and therapeutics to see
how quickly scientific research can result in widespread
benefit.
Many diseases which would have resulted in a patient's
death just a few years ago can now be treated and, in some
cases, cured by FDA-approved therapies. While FDA has approved
countless transformative therapies for life-threatening
diseases, these stand in stark contrast to the conditions for
which there are few or no available treatment options.
I applaud the subcommittee's attention to this topic by
holding this hearing today.
Neurodegenerative disease has caused tremendous suffering
for patients and their loved ones. We need to adopt additional
innovative approaches for these diseases to bring new drugs to
people who desperately need them. There are three primary
elements to our approach that I want to highlight today: the
need for more research, employing regulatory flexibility, and
actively listening to the people stricken by these terrible
conditions.
Neuroscience is an area of medicine where there is
tremendous unmet need for safe and effective treatment and for
research that can guide and inform the development of new
therapies. Although there has been great progress in basic and
preclinical research for neurodegenerative diseases, we have
yet to identify the key underlying molecular defects that give
rise to many of these conditions.
The current limitations present significant challenges for
drug development. This holds true for ALS. For instance, in ALS
and many other neurodegenerative diseases, there are no easily
measured biomarkers that are reliable predictors or surrogates
for the rate of disease progression in individual patients.
Such tools would improve the precision with which drug response
could be evaluated, leading to more robust and earlier insight
to distinguish the more promising drugs from those that are
less likely to succeed.
Researchers are continuing to make advances in
understanding the underlying causes of neurodegenerative
diseases, and this holds promise for drug development.
As an agency, we are using every tool at our disposal to
help facilitate the development of treatments for these
diseases. We have long stressed the need to exercise regulatory
flexibility in applying the statutory standards when it comes
to medical products for serious diseases with unmet medical
needs, while making sure that these are effective and have a
favorable benefit-to-risk profile. This flexibility flows from
the statute and through our regulations and guidance.
In the meantime, we understand the need for access to
therapies when people with life-threatening diseases cannot
participate in clinical trials. This is why the agency grants
almost all individual patient expanded-access requests.
However, an essential step in the expanded-access process is
the company's willingness to provide the drug. And there are
instances when this doesn't happen, for reasons such as ongoing
clinical trials, financial burden, or insufficient drug supply.
We do all we can in these situations to help people who
desperately need these drugs.
Finally, the capstone of all our efforts are the people who
need therapy. Their experiences, perspectives, and priorities
are a critical aspect of drug development. Patient-focused drug
development enables the delivery of therapeutics that have a
meaningful impact on people's quality of life and target what
they consider the most important aspect of their diseases.
I look forward to discussing these and other issues with
you today. We recognize the impact these devastating diseases
have on patients and their loved ones. We share the sense of
urgency. And, as an agency, we stand ready to make full use of
our authorities in order to help bring new therapies to people
with these diseases as quickly as possible. Thank you.
[The prepared statement of Dr. Cavazzoni follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Ms. Eshoo. Thank you, Dr. Cavazzoni.
We are now going to move to Member questions, and the Chair
recognizes herself for 5 minutes to do so.
First, to Dr. Cavazzoni, in your written statement you say
that a treatment that provides meaningful incremental benefit
would still be desirable. Now, many of the ALS advocates think
that the statistically significant outcome in the Amylyx trial
that showed a near three-point improvement was incremental but
meaningful.
Now, as we all know, these are individuals who are usually
told they only have 2 to 5 years to live. And what I want to
examine is--because there is a discrepancy, I think, between
FDA and incremental--meaningful incremental benefit, being
desirable, and actually approving a drug that produces that.
So would you comment on that, and tell us how you define
meaningful incremental benefit?
[Pause.]
Ms. Eshoo. You need to unmute.
Dr. Cavazzoni. Thank you, Chair Eshoo, for that question.
We generally don't comment on a specific drug program, as some
of the information is sensitive.
Having said so, generally----
Ms. Eshoo. But Doctor, in general, in general. I understand
that you can't comment on specific drugs. I just used that as
an example. But in general, how do you define incremental?
Dr. Cavazzoni. So, in general----
Ms. Eshoo. See, I think that, you know, the context here is
that incremental, in these cases, is small. But it represents a
great deal of hope to people that are living with a death
sentence.
Dr. Cavazzoni. So, in general, we look at incremental
benefit and incremental gains from a--from several points of
view. The perspective of the patient is very important to us,
because what we hear from the patient is--it really guides us
as to what they view as meaningful incremental gains.
And what we have heard from people suffering from ALS, for
instance, is that improvement in symptoms and improvement in
quality of life is very important, in addition to lengthening
of survival. And so we have actually reflected these
perspectives in how we guide developers running programs for
treatment for ALS, and this is actually reflected in our
guidance on developmental drugs for ALS, where we point out
that we--developers should be looking at a variety of
endpoints.
For instance, not only for----
Ms. Eshoo. Let me--I need to interrupt you because I need
to get another question in, and it deals with the European
conditional approval pathway. They have a different system.
When they approve--when the drug is approved, on the condition
that they will be evaluated further while on the market. We
don't do that in the United States. And this means that the
Amylyx drug may be available to European patients 2 to 3 years
before American patients.
So if FDA had a similar authority for a conditional
approval pathway, would that give the FDA more flexibility in
getting potentially promising therapies to dying patients
sooner?
And if so, would the--does the FDA seek that kind of
legislation in Congress for a conditional approval?
Dr. Cavazzoni. So thank you for that question. That is a--
it is a very important question.
The--when it comes to approaches to expedite development of
a drug for life-threatening diseases, we think we have a lot of
tools at our disposal and that the limiting factor in applying
all of the tools that we have, such as accelerated approval,
for instance, is really the lack of understanding of the
biology of the diseases. And we are very eager to work with
sponsors to identify some of the biomarkers and the markers of
the disease that would allow us to utilize our expedited
pathway, including accelerated approval, in neurodegenerative
diseases to accelerate the development.
Ms. Eshoo. Well, my time is expired, and the Chair now
recognizes Mr. Guthrie, our ranking member, for his 5 minutes
of questions.
Mr. Guthrie. Thank you, Madam Chair, for the recognition,
and the first question is for Dr. Koroshetz and Dr. Hodes.
As you know, the NIH BRAIN Initiative is intended to
produce a revolutionary new dynamic map of the brain that can
show how individual cells and complex neural circuits interact
in both time and space. How will this initiative--the question
for you two--how will this initiative improve our knowledge of
neurodegenerative disease and help researchers find new ways to
treat, cure, and even prevent these diseases?
Dr. Koroshetz. Well----
Mr. Guthrie. Dr. Koroshetz?
Dr. Koroshetz. Yes, thanks very much. So this is really--I
was talking about this, but I won't--I will say basically three
things.
One is that we now have the ability, after amazing
discoveries--try and get a census of the human brain. That is
our transformative project that we are launching now. And that
was enabled by technologies that allow us to look at single
cells and analyze what is inside those single cells. But
instead of 400 cells over 6 months, we can do a million cells
in a few days. And that now is an amazing----
Voice. It is amazing, isn't it?
Dr. Koroshetz [continuing]. Study the brain of people with
neurodegenerative diseases, and we will be able to tell what
cells are missing. We will also be able to tell what is the
difference between a sick cell and a healthy cell as the
disease progresses.
The second thing this will allow us to do, which is really
amazing, is that inside these cells there are, like, genomic
keys that open the door to the cell. And what we are trying to
do is to find those keys for every specific cell and then link
them up to a genomic therapy that, when we give it to the
person, it will only go into the cell that needs it. And that
is--that kind of precision targeting will be absolutely game-
changing.
And the last one is that, as a neurologist, we see the
patient and we see what symptoms they have, and then we look in
the brain and we see what kind of pathology we see. And we say
pathology caused the symptom. But what is in between is the
circuits. And we had no way of seeing those circuits. But now,
with the BRAIN Initiative technology, we can see those circuits
in action, which is really exciting. So the circuit, this
function itself, becomes the target.
And for instance, just an example, there is a study of
people who do not have any dementia, they are perfectly normal,
but their brains look like they have terrible Alzheimer's
disease. So an example--the pathology is fooling us. The
circuits are still healthy. And so these kinds of things can be
explored with the tools of the BRAIN Initiative.
Those are the three things that I would offer up----
Mr. Guthrie. OK, thank you, I appreciate that. I want to
ask Dr. Hodes, instead of answering that question, that second
question, you can emphasize--you can go back to that one, if
you would like.
But Dr. Hodes, as you know, caring for a person with
Alzheimer's disease or other dementia poses unique challenges.
Nearly all people living with dementia experience at least one
neuropsychotic symptom, which can include anxiety,
irritability, agitation, depression, hallucinations, and
delusions. And these are challenges, a leading reason that
prompt--family caregivers decide to place their loved ones in
institutional care settings.
So the question is--and you can respond to the other one,
as well--but do you believe that providing individuals living
with neuropsychiatric symptoms and dementia in their family
with safe and effective treatments is an important priority?
But also, would you update us on the search for treatment
options to address this unmet medical need?
Dr. Hodes. Thank you, and a very important question. As I
alluded to briefly and can reinforce now, research--ways in
which to maximize quality of life and care for those living
with dementia is as current and imperative as our searching for
the cure itself. And there are currently over 80 studies funded
by NIA alone trying to understand which are the most effective
of these interventions, so they can be promulgated.
Some already have. REACH is one, for example, that was a
result of an NIA-sponsored trial some years ago that has been
promulgated through the VA and through Indian Health Service as
one of the examples. But we are constantly looking for ways in
which, through the pragmatic clinical trials I mentioned,
randomized trials, every bit as rigorous as a drug trial,
trying to look at the very best kind of intervention. And we
are learning more and more about this every day.
So our ability to translate this to real care is on the
horizon and happening now.
If I could just very briefly amplify on what----
Mr. Guthrie. If you--just some breakthroughs you see
coming, yes, some breakthroughs you see coming.
Dr. Hodes. Well, in terms of caregiver support?
Mr. Guthrie. Yes, just in Alzheimer's research, yes.
Dr. Hodes. Well, in Alzheimer's research, in general, just
a good point to start is amplifying what Walter Koroshetz
described, the enthusiasm that I think we all share. This
incredible ability to look at the levels of individual cells
and circuits that we never had before begins with the basic
science.
So these initial studies are done in normal brains, in
animals, and then in humans. But it immediately provides the
opportunity for breakthrough, as Walter alluded to, for
diseases such as Alzheimer's. And now to find out what is--what
we have already learned, when we look at the genetics, the
profiles of--cell and molecular biology in brains of patients
with Alzheimer's, from--they are not all the same. So we are
now poised, as never imagined before, to look at ways to
intervene and target through some of the strategies Walter
mentioned at a very----
Mr. Guthrie. Dr. Hodes, I think I have let you run over
time, so I am going to have to stop here. Hopefully, we will
hear more as we go through. I yield back.
Dr. Hodes. Thank you.
Ms. Eshoo. The gentleman yields back. I thank you, Doctor.
The Chair now recognizes the chairman of the full
committee, Mr. Pallone, for his 5 minutes of questions.
Mr. Pallone. Thank you, Chairwoman Eshoo.
One of the strategies that has been discussed in witness
testimony today is bolstering expanded access, sometimes called
compassionate use. Expanded access allows patients with serious
or life-threatening conditions with no satisfactory
alternatives, and who cannot enroll in a clinical trial, to
access an unapproved investigational drug if their physician
says that the potential benefit justifies the potential risk
and that providing access won't interfere with an ongoing
clinical trial. And I have some questions about expanded
access.
First to Dr. Cavazzoni, in 2017 former FDA Commissioner
Scott Gottlieb testified before this committee and said that
FDA approved expanded access requests 99 percent of the time. I
wanted to know two questions.
One, is that still the case? And if so, why do some
patients still have difficulty accessing drugs under the
program?
And second, what reasons would manufacturers have for
declining to participate in expanded access, if you would?
Dr. Cavazzoni. Thank you for the question, Chairman
Pallone. I can confirm that we are still approving the
overwhelming majority of expanded access, individual patient
expanded-access applications. And between--over the past 5
years we have approved close to 98 percent.
There are reasons for companies not making the drug, an
investigational drug, available through expanded access. And
the first one, and most common, is the fact that there may be
an ongoing clinical trial with that drug and that the patients
who are asking for expanded access may be eligible for that
clinical trial, or they may be concerned about slowing down the
recruitment of a clinical trial that could provide important
answers on the drug.
For smaller companies, what we have also seen is that there
may be some financial constraints in supporting an expanded-
access program. And sometimes we also see some issues with the
limitations in the drug supply when all of the drug supply has
to be devoted to an ongoing clinical trial, for instance, or
again, due to some financial considerations, particularly with
the smaller companies.
Mr. Pallone. All right. Now, some have said that expanded
access can improve research into neurodegenerative diseases,
because more data would be generated from patients on the
treatment. So let me go to Dr. Koroshetz.
Can you speak about NIH's view on whether data generated
through an expanded-access program could be useful for
scientific research?
And how would NIH consider research proposals based on data
generated from an expanded-access program?
Dr. Koroshetz. Right. So that is a very good point, to try
to differentiate the finances of expanded access and the
scientific value.
So for NIH, in a trial, the greatest value would be in
continuing access to patients who are enrolled in the trial
after they have finished the trial. That--because then you have
a comparator group, and you can check for durability of any
result that was found. And then you can also do a crossover of
patients who are on placebo and then get on active treatment.
And you get information from that.
It is very hard to get--unless there is a tremendous effect
size, it would be very hard to get scientific value out of a
broad expanded access unless the treatment has a very big
effect size. But if it is a smaller effect size, then you
wouldn't be able to tell that there has been a change in the
condition.
Mr. Pallone. OK, can I ask--I mean, thank you so much. Let
me go back to Dr. Cavazzoni.
Can you explain why a clinical researcher might choose to
exclude a patient who has participated in an expanded-access
program from participating in a trial?
Is it possible to put safeguards in place to ensure that
expanded-access participation doesn't harm clinical trial
enrollment?
Dr. Cavazzoni. I cannot hypothesize why an individual
researcher may decide to exclude a patient from a specific
clinical trial. However, in general, studies routinely allow
prior exposure to investigational agents, including potentially
expanded access, after a suitable period of time when the
patient has been off that investigational agent. And there may
be some situations where the developers may have concerns that
the prior exposure to an investigational agent may have an
impact on the conduct of the clinical trial or the
interpretation of the results.
When it comes to what we do at FDA, we are very sensitive
to this, and we routinely work with sponsors to attempt to
ensure that they do not use overly restrictive or unnecessary
criteria to exclude patients who have been on investigational
agents. And this is really part of our broader commitment to
making sure that trials are inclusive when it comes to the
diversity of patients that are included in the clinical trials
and the full scope of the manifestations of the disease,
particularly in----
Ms. Eshoo. The gentleman's time has expired. The
gentleman's time has expired. The Chair now recognizes the
ranking member of the full committee, Mrs. McMorris Rodgers,
for her 5 minutes of questions.
Mrs. Rodgers. Thank you, Madam Chair.
Dr. Cavazzoni, FDA has been working on inclusivity of
clinical trials. But as today's hearing is demonstrating,
there's still a lot of patients desperate for access to drugs
still in development that cannot get access. How do we
appropriately address concerns about the need to broaden
eligibility for clinical trial participation?
And would you speak specifically towards the guidance FDA
has provided, if any, about those, including people with Down
syndrome in clinical trials designed to support drug approval?
Dr. Cavazzoni. Thank you for that question. We have been
putting a lot of thought in how to improve the diversity of
representation in clinical trials. And as you have referenced,
we have recently issued guidance to instruct or help developers
on how to expand the eligibility to clinical trials and to find
ways to make sure that underrepresented populations,
including--beginning with racial and ethnic minorities, are
included in these clinical trials. And we are continuing to
work to really make sure that we--that developers are--follow
our guidance.
When it comes to the progress that we have done so far, we
have seen over the past several years that there have been some
gains when it comes to representation of women, racial and
ethnic minorities in many therapeutic areas. There are certain
therapeutic areas where there is still more work to do,
including, for instance, trials of Alzheimer's disease. And we
are very focused in working with developers to make sure that
they deploy all the tools that are available to them, or even
new tools that they may be able to identify to expand the
diversity of the populations that are----
Mrs. Rodgers. Mic isn't on. That might help. OK.
Dr. Cavazzoni, thank you. I wanted to highlight the issue
of individuals with Down syndrome, because, as I mentioned in
my opening statement, 100 percent of them are developing
Alzheimer's, and yet they are not being included the way I
believe they should, that we should embrace what we could learn
from those with Down syndrome, with that extra twenty-first
chromosome, when it comes to research and really including them
in clinical trials. They develop juvenile leukemia at a higher
rate, but no tumor cancers. Let's embrace what they could--what
we could learn from those with Down syndrome for so many
others.
Dr. Koroshetz and Dr. Hodes, individuals with Down syndrome
experience a lifelong, chronic autoinflammation. While FDA just
granted accelerated approval for antiamyloid therapy, is NIH
exploring alternatives, such as research to explore the use of
therapies that modulate the immune system to slow down or even
reverse Alzheimer's disease and other neurodegenerative
diseases?
Dr. Hodes. Yes, thank you for that specific question. As I
alluded to, the diversity of targets that are now being
involved in clinical studies, clinical trials, that has
expanded, obviously.
So for, for example, in the more than 50 clinical trials
now at NIA for drugs, the majority of them are looking at
targets other than amyloid and tau. Among them are the
pathways--inflammation and the immune system. This is coming
from information--science, as well as the nature of the
pathology seen, so very much so [audio malfunction] to the
inclusion and the importance of including Down syndrome as a
population very vulnerable to Alzheimer's disease. It has been
a pleasure working with you over the past years.
And, as you know, currently ongoing is the ABC, the
Alzheimer's Biomarker Consortium for Down syndrome, which is
very rapidly putting together a cohort of individuals who are
studied for the progression of the disease by biomarkers and
will provide a very important basis for their inclusion in
intervention and clinical trials, as appropriate, as well.
Mrs. Rodgers. OK, thank you. Are there any efforts being
funded at NIH or private entities to analyze neurodegeneration,
brain inflammation, and other accompanying processes from birth
to life?
And what about research to identify other early life events
that may predispose individuals with Down syndrome to
Alzheimer's disease?
And would you just discuss further work in this space in 11
seconds?
Dr. Hodes. Yes. Again, as you know, and under the rubric of
INCLUDE, where many institutes, including NIA, are
participating, there is a multifaceted study looking at the
role of inflammation as--central nervous system, but also other
autoimmune disorders, the cardiovascular disorders, which are a
part.
So I think we have been very effective, as a consortium,
across institutions, across all of NIH, in collaborating and
focusing those efforts on the population--critical to the
population [audio malfunction].
And as you point out also, very informative to the
components of the----
Mrs. Rodgers. Thank you. Thank you for being with us, and
for your work.
I yield back, Madam Chair.
Ms. Eshoo. The gentlewoman yields back. The Chair is
pleased to recognize the gentleman from North Carolina, Mr.
Butterfield, for your 5 minutes of questions.
Mr. Butterfield. Thank you very much----
Ms. Eshoo. Please unmute.
Mr. Butterfield [continuing]. Chair Eshoo, for convening
this very important hearing. And thank you to our witnesses for
your testimony today. Thank you for your dedication, and thank
you for your brilliance.
This is an issue that we should be able to embrace on a
bipartisan basis. And so I want to begin to develop this with
Dr. Cavazzoni.
Thank you for your testimony and your incredible work at
FDA. You noted in your testimony that, although great progress
has been made in treating and curing some conditions, you said
the progress has not been even. Later today we will hear from
patients and caregivers and researchers who will share what the
human cost of this failed progress is.
FDA appeared to recognize the human cost when it released
its 2019 guidance on ALS drug development. But since then it
has denied approval for two ALS drugs. And so I would like to
better understand how FDA is applying its guidance in practice.
One promising therapy, I think, was recently rejected by
the FDA, even though it showed a 30 percent slowing in
disability, and a 6-month prolongation in survival for a subset
of patients. And so my understanding is that the basis of the
rejection was a perceived need for a confirmatory trial. And so
I am told that such a trial will take 3 to 4 years, during
which time half of the 20,000 Americans currently living with
ALS will leave us.
And so FDA said, in its 2019 guidance, that it understood
the appropriateness of exercising regulatory flexibility for
serious diseases with unmet medical needs--end of quote.
That is a long opening statement. Here we go. Here is my
question: Why hasn't FDA employed this flexibility for ALS
treatment, when it has demonstrated its willingness to be
flexible with the emergency use authorizations in other areas?
Dr. Cavazzoni. Thank you for your question, and you are--
the questions that you raise are really very important, and
core to how we view our work.
We are operating in a manner that is fully consistent with
our guidance, understanding that there has been a lot of hope
that has been pinned on certain therapies, and that,
unfortunately, there may have been disappointed--disappointment
with some programs. Our guidance, and the way we operate,
recognizes that, first and foremost, there is a higher
threshold for risk in patients who are suffering from diseases
such as ALS, because they are so rapidly progressive and
lethal.
And we also, as we look at how to guide developers and how
we interpret the data that they put in front of us, we take
into consideration the fact that we--there has to be a higher
threshold for risk, and also that we may be in situations where
we may have--I have to accept some degree of uncertainty around
the benefit in these particular diseases.
Mr. Butterfield. All right, let me move on to the next
question. This 5-minute timeframe goes very quickly.
My staff, a few days ago, had the opportunity to speak with
the director of the Duke--that is Duke University--ALS Clinic,
which is right near my district. The director shared that he
has taken care of over 3,000 ALS patients in his entire career,
most of whom could not find a place in a clinical trial. And
so, out of desperation, his patients are self-experimenting
with treatments they buy from the internet.
Not only are patients likely suffering financial and health
harms from self-experimentation, but the research community
suffers because this is not properly studied. I think everyone
would agree that an access program with appropriate oversight
and study would be preferable to self-experimentation.
I realize FDA cannot require a company to offer a product
under expanded access, but can FDA incentivize participation or
leverage research generated from the expanded access program?
Dr. Cavazzoni. We work very actively with sponsors to
establish expanded-access programs. And, in fact, there have
been instances where we have repeatedly asked sponsors to offer
a drug under expanded access, and the sponsor has not been
willing or able to do so.
And we also see the utility in data that is gathered from
expanded-access programs, particularly when it comes to rare
diseases, where we try to accelerate the development by not
requiring as large of a safety database that we would normally
do so. And so we value the expanded-access programs when those
are put in place, as a way to also----
Mr. Butterfield. Thank you. I am going to have to ask you
to stop for a moment.
Madam Chair, I yield back. There is much more to go on
this, but we will try it if there is a second round. Thank you,
I yield back.
Ms. Eshoo. The gentleman yields back. And thank you for
your excellent questions, Mr. Butterfield.
The Chair is pleased to recognize the gentleman from
Michigan, Mr. Upton, former chairman of the full committee, and
a Member that we all have deep regard for.
You are recognized for your 5 minutes of questions.
Mr. Upton. Well, thank you, Madam Chair, and--for chairing
this incredibly important hearing. And I appreciate the
testimony by the witnesses, not only on this panel, and I have
read through the testimony of those that are coming on the
second panel, as well.
I want to just remind my colleagues that when we embarked
on 21st Century Cures, important legislation that every one of
us then on the committee supported 53 to nothing back in 2016,
we worked with the FDA, we worked with the agencies, we worked
with the patient groups. And we asked a lot of questions: What
could we do to advance the cures for these diseases that
impacts everybody?
You know, my neighbor next door, he died of ALS, a lot of
friends with Parkinson's. We know people that are getting
cancer and, hopefully, cured. That rate has, thank goodness,
gone up.
And I would recommend the reading of Michael Milken's piece
in the op ed page yesterday in the Wall Street Journal. He
talks about where we can go for now.
And the chair was with me, along with Mr. Guthrie, with the
President back in March, when he talked about ARPA-H, and that
is an important thing. That is an element, a new element, that
is going to be funded in the Labor-H appropriation bill and
ultimately will get to the President's desk.
And Diana DeGette and I are working again on a Cures 2.0
bill that will be included. But as part of 21st Century Cures,
what we did was we also asked the FDA, what could we do to help
you do your job better? How do we find the cures? How do we
help you approve the cures earlier, so that we can deal with
these folks and not have them languish and die before their
lives can be bettered or, hopefully, find a cure like we did
with CF, cystic fibrosis, and some other things, sickle cells--
and a remarkable achievement, in terms of what went on.
And so I know, Dr. Cavazzoni, you have been--you have got
an important role, and I appreciated your testimony, and I have
looked at the testimony of the next panel that is coming and
read it, and I know--you know, particularly the ALS community
is so frustrated. You know, there is not a cure to better their
lives. Can we extend them, so they can do some things that are
certainly more functional, and provide the hope that at some
point we will have a cure?
I think that is a frustration that all of us share with
their group, and I know that, when I look at the testimony from
the ALS Association, which is coming on the next panel--which
probably won't be until late in the day, because we are going
to have a whole series of votes--but they ask, rightly so, a
number of questions.
The FDA must be fully funded and fully staffed and provided
the regulatory authority, and that is--we asked that question.
We asked that question of then-Director Hamburg and Janet
Woodcock and others: What can we do? And they gave us a dollar
figure, and we did it. We actually increased it.
But I guess the question that I have for you on this panel
is, what can we do now to give those folks who have ALS the
hope that their lives will be frozen, will be better while they
are still here?
And I am just curious to know, is this really--following up
on my good friend Mr. Butterfield's comments about the
wonderful research that Duke has done, but other universities
as well--what can we do to help you do a better job to provide
the hope that these folks want? That is my question.
Dr. Cavazzoni. Thank you for that question. And I am, you
know, very, very sensitive to the--how frustrated the ALS
community are, and share the sense of urgency to bring
therapies, to deliver therapies to patients with ALS.
When it comes to the tools that we have at our disposal, we
have the same tools at our disposal when it comes to regulatory
flexibility that have led to tremendous advances in oncology.
Those are really the same tools.
Where we are experiencing some limitations and some
challenges is in the fact that they are--we don't have as good
an understanding of the biology, the genetic underpinnings, the
biomarkers in many neurodegenerative diseases. And those are
the elements that have allowed us to fully deploy the expedited
regulatory pathways that we have available, such as accelerated
approval, such as breakthrough therapy and so on, in
therapeutic areas such as oncology, where we have made
tremendous gains over the past 20 years.
And so as we--as the understanding of the biology improves,
we are doing everything that we can to work collaboratively and
proactively with developers of drugs with ALS and other
degenerative diseases to advance their clinical trials and to
understand the data that we obtain through clinical trials,
which sometimes is complex, and requires working very closely
with the developers.
Mr. Upton. Time has expired.
Ms. Eshoo. I would just like to make a remark, and that is
that, even though you don't have the biomarkers, you know what
the outcomes are. And I think that that is an area that we need
to hear more about from you. Maybe it is not a leapfrogging
advance, but it is an advance. It demonstrates something, and
that means a great deal to those that bear this godawful
disease. So I just want to get that down for the record.
The Chair is now pleased to recognize the gentlewoman--and
that she is--from California, Ms. Matsui, for her 5 minutes of
questions.
Ms. Matsui. Thank you very much, Madam Chair, for calling
this very important hearing, as everyone can see by the
expressions of the emotion that we have around the issue of
neurodegenerative diseases. The reason why is we have so many
friends and constituents who--from all kinds of backgrounds--
have suffered in many ways, which have Parkinson's,
Alzheimer's, ALS. We can go on and on. So this is an issue area
that is so critical for all of us. So I want to welcome all the
witnesses joining us today as we try to untangle this and try
to find a path forward.
Now, last week I introduced the BENEFIT Act. It is
legislation to ensure that patient experience and patient-
focused drug development data can be considered as part of
FDA's benefit/risk framework for drug approval. Today's hearing
is timely, as patient-centered research is essential to drug
development for neurodegenerative diseases. The 21st Century
Cures Act required FDA to report to Congress on the use of
patient experience data and regulatory decision making, and the
first report was released just last month.
Dr. Cavazzoni--and I realize you feel you are on a hot
seat, but the FDA is so critical--the report said that the
variability in FDA's use of patient experience data may be
reflected by the range of diseases it regulates. What can you
tell us about FDA's use of patient experience data for
neurodegenerative diseases, Dr.----
Dr. Cavazzoni. Thank you.
Ms. Matsui [continuing]. Cavazzoni?
Dr. Cavazzoni. Thank you for that question. We are very
sensitive to the input of patients' experience in drug
development, in how clinical trials are designed, and in
identifying endpoints.
And so, to--as an example, if we look at the guidance that
we have issued around the development of drugs for ALS, we not
only provide a lot of information and advice to developers when
it comes to the endpoint that they could use to study drugs for
ALS, even in the absence of biomarkers such as, for instance,
muscle strength or function, or even breathing function and so
on, so that they have a host of potential endpoints that they
can use to design clinical trials and find answers quickly.
And in addition to that, in the guidance and as we work
with developers, we also emphasize the importance of patient-
reported outcomes, not only for ALS but also for other
neurodegenerative diseases, such as, for instance, Alzheimer's.
And recognizing that the caregiver is also very important in--
when it comes to the lives of patients who suffer from
neurodegenerative diseases, we also encourage the use of
endpoints, or scales, or measures that allow us to also----
Ms. Matsui. I am going to interrupt you, Dr. Cavazzoni. I
wanted to also ask you about the conditional approval
proposals, and I believes others have talked about this, the
chairwoman, which have been put forward to allow approval of
drugs before full safety and efficacy data is developed through
phase three clinical trials if relevant, early evidence based
on early-stage clinical trials shows that there could be a
positive therapeutic outcome from the drug.
Now, can you explain how this standard is different from
what FDA currently uses for full approval and accelerated
approval?
And what are the risks of adopting a provisional or
conditional approval standard?
Dr. Cavazzoni. There are some similarities between, for
instance, accelerated approval and a conditional approval
pathway that exists in Europe in the sense that they both
recognize that, when that pathway is used, there is still some
degree of residual uncertainty around the drug's benefits.
Having said so, there's also some notable differences
between the two. When we look at the tools that we currently
have at our disposal, we really have an array of tools,
starting with accelerated approval, that allow us to make
determinations about benefit/risk and decide whether to approve
a drug before we have, for instance, in some instances, have
completed phase three trials. And there are some very good
examples in oncology where drugs have been approved----
Ms. Matsui. OK, and could I just say this? I think what we
are very interested in, as we talk to people about their
particular situation--and I am looking at the fact that many
people don't have a lot of time and, quite frankly, some of
this depends upon the particular disease you have, and the
pathway.
And so I would hope that we could focus a lot on how we
might expedite these processes more safely and look at some of
the patient type experiences that we have had.
And with that, Madam Chair, I yield back.
Ms. Eshoo. The gentlewoman yields back. The gentleman from
Texas, Dr. Burgess, is recognized for his 5 minutes of
questions.
Mr. Burgess. I thank the chair, and I appreciate the fact
that we have agency witnesses here today. We don't have nearly
enough hearings involving agency personnel. And, for whatever
reason, it is very, very difficult to get telephone calls
answered from the agencies.
So, Dr. Cavazzoni, I am--forgive me. I am going to ask you
a question, and I know your answer is going to be ``That is not
my department,'' but people just have to know why. Why has it
taken over 8 months into the data safety monitoring board
releasing the data on the Pfizer vaccine? December 8th or 12th
was the emergency use authorization. Why has that not received
either full authorization or been withdrawn from the market?
Why are we still left guessing here?
[Pause.]
Voice. Patrizia, you are on mute.
Dr. Cavazzoni. My apologies. Unfortunately, I did not come
prepared to answer questions in this area today.
Having said so, I would be pleased to come back to you and
your staff with answers to your questions.
Mr. Burgess. Yes, I would like that very much. And it is
very frustrating. We can't--we call with questions. I have had
a call into the CDC for several weeks, and we get no response.
And we are in the middle of this pandemic. And your agency and
our committee needs to work very closely, and it is--right now
I get the impression that it is not happening the way it
should.
Now, having gotten that off my chest, Mr. Upton's remarks
are similar to what I was going to bring up. I was on this
committee, this subcommittee, when we worked through the 21st
Century Cures Act. It really was a novel approach to the--to
that type of legislation. We had--it was understood at the
start that it would probably take more than one Congress to
work through and develop the bill and understand the processes.
We had hearings, briefings, field hearings. I personally
attended 15 different field hearings around the country,
hearing from people.
And it does--in the Alzheimer's space, you know, as you can
imagine, it has been intriguing for several years. It makes an
appearance, and then it is withdrawn and then goes through an
advisory committee, and it was controversial, and now it has
received conditional approval. But--and I would appreciate more
information on this, but it seems like that is exactly what we
talked about with Cures. We have a surrogate endpoint, and--
which is the, I guess, the development of amyloid or tau, and
we have a drug to which to apply it. And the whole problem is
how do we get to some answers before everyone expires.
I mean, it just seems to take so long, and that was the
whole purpose of Cures: How do we reduce the time from lab
bench to bedside? And I understand that I don't know everything
that was involved with Aduhelm's approval, and then conditional
approval, but it just seems like that followed the pathway that
we had outlined in Cures in order to reduce the time from the
lab bench to the bedside.
Now, in 2008 the ALS Registry Act was signed into law with
the goal of understanding and identifying ALS-associated risk
factors. Granted, the registry is administered under the
Centers for Disease Control. But are you at the FDA aware of
any efforts from the FDA to utilize the data at the registry?
Dr. Cavazzoni. I can't think of any specific instances
right now. This is something that I would be able to--would be
happy to get back to you after the hearing.
Mr. Burgess. OK, and I would appreciate that very much.
And again, I would just underscore--and brought up by Mr.
Butterfield and Chairman Upton--that one of the most
substantiative victories achieved in my time in Congress was
the passing of the 21st Century Cures Act. And it did provide
hope for so many families who had been suffering from a long,
life-altering illness.
I just want to point out, during the work on the Cures, I
felt very fortunate to be able to include a stand-alone bill to
establish a national neurologic condition surveillance system.
Prior to us passing the Cures Act there was no official
structure in place to provide surveillance of neurologic
diseases. So I am very grateful that that has been established.
Now we need to take the next step. We need to utilize that
information and deliver the benefits for our patients. Thank
you, Madam Chair. I will yield back.
Ms. Eshoo. The gentleman yields back. The Chair is pleased
to recognize the gentlewoman from Florida, Ms. Castor, for her
5 minutes of questions.
Ms. Castor. Well, thank you, Chair Eshoo, for holding this
important hearing, and for your devotion of so much time,
always, to cutting-edge research. And thanks to our witnesses
today for your important work.
I am committed to advancing treatments and cures for
neurodegenerative diseases. In Florida about 580,000 Floridians
aged 65 and older suffer from Alzheimer's. Over 1,300
Floridians are living with ALS. Florida has the highest
percentage of individuals with Parkinson's in the country.
Now, in my neck of the woods, in the Tampa Bay area, we are
very fortunate. We have a research university at the University
of South Florida that is leading research on neurodegenerative
diseases through the Department of Neurology. They--we have a
world-renowned USF Byrd Alzheimer's Center. They do a lot of
important research that is family-centered, compassionate, in
partnership with patients and advocates. They do the same with
ALS patients. They have a clinic solely focused on ALS
patients, with families and caregivers there. They really
believe in the interdisciplinary approach.
And of course, we have a number of clinical trials with the
university community, industry as well. So robust and
consistent support for NIH and FDA is paramount here.
Dr. Cavazzoni, I want to ask you a little bit about recent
guidance from FDA. Guidance to industry is very important to
help direct work. It is my understanding FDA has released draft
guidance for industry stakeholders seeking to develop
treatments for ALS, that currently has no known cure and very
few approved treatments.
The guidance says that FDA will consider patient tolerance
for risk and the serious and life-threatening nature of the
condition in the context of statutory requirements for safety
and efficacy.
It also describes considerations for drug makers should--
that they should make at various points during drug development
and encourages industry to work with the FDA throughout the
process.
Now, FDA does not often release disease-specific guidance.
Why did FDA develop specific guidance for ALS?
Dr. Cavazzoni. Thank you for the question. We have released
a host of guidances that are sort of specific to certain
diseases. And we do so in the instance for--of ALS, for
instance, when we recognize that there may be particular
challenges in the development of therapeutics for those
diseases. And certainly, neurodegenerative diseases are very
much part of those situations.
We have worked on the ALS guidance in collaboration and
listening very carefully to the feedback from the ALS community
and what we heard from the community and researchers and
treating physicians as to the aspects of development that were
particularly challenging.
And certainly, when we look at the--what we lay out in the
guidance, we do make the point that we recognize that the
tolerance for risks, when we are developing drugs for diseases
such as ALS, is greater. And we do recognize that in our
thinking about the benefit versus risk, as we evaluate the data
that are provided to us by sponsors and are yielded by clinical
trials.
Ms. Castor. So the guidance says that developers should not
unnecessarily exclude patients from trial enrollment based on
characteristics such as age or disease stage, unless
scientifically justified, and suggests that, even if they are
testing a subset of patients for a primary analysis of
effectiveness, they can include a broader population in the
trial for secondary and supportive analysis.
How has industry responded to the guidance, especially when
designing clinical trials?
Dr. Cavazzoni. Well, industry has generally been receptive
to this advice. Some of the challenges that has--that sponsors
have encountered is that--in the fact that they are--in the
limitations, in some instances, in being able to identify
biological markers for some of these populations.
So, for instance, we know that ALS has--it is largely----
Ms. Eshoo. The gentlewoman's time has expired, the
gentlewoman's time has expired.
The Chair now recognizes the gentleman from Virginia, Mr.
Griffith, for his 5 minutes of questions.
Mr. Griffith. Thank you very much, Madam Chair.
Dr. Koroshetz, a swimming friend of mine who has ALS
recently participated in a National Institutes of Health study.
He was very pleased with the way it was conducted, once it
finally began. But recruitment for the study started about a
year before it began, despite the study only needing 25
participants. I think we can all agree it should take weeks,
maybe days to fill only 25 slots.
Tell me about your recruitment process, who is involved.
How is information disseminated, such as to doctors and
patients and to advocacy groups, so that they know that there
is a study available?
And is there an appropriate sense of urgency at the NIH?
Dr. Koroshetz. Well, there definitely is a sense of
urgency, and everybody who knows ALS realizes [audio
malfunction].
In general, ALS trials are actually better than even--than
most. The ALS community is a very tight community, we can't--
have very good ties with the ALS Association. And generally,
you know, because they are--the community is really looking for
answers, we have, generally, not had trouble with ALS.
Now, you will talk to Merit Cudkowicz in the next panel,
and she runs the platform trial for ALS. She could maybe have
more--on this. But my understanding is ALS is actually doing
pretty well, in terms of enrollment.
If you send me any information about the particular one you
are mentioning, I would be happy to look into it.
Mr. Griffith. Well, I would be happy to send you the
information, but, I mean, you are saying that ALS is doing
pretty good, and getting, you know, people into the studies.
Dr. Koroshetz. Yes.
Mr. Griffith. My friend's experience was it took him over a
year before they got enough participants, and they only were
looking for 25. That doesn't sound like we are doing good
enough, and that we maybe need to do more.
It doesn't sound like you have any ideas. But look, we are
here, trying to help.
Dr. Koroshetz. Yes.
Mr. Griffith. If there is something we need to be doing, if
there is--you know, you need authorization to advertise, as I
sometimes hear for clinical trials, if you need to advertise
and we haven't approved language for that, then let us know,
because we want to help. We want to try to solve this problem,
because he is not doing very well, he is not doing nearly as
well as I would have hoped.
Dr. Koroshetz. Yes, yes.
Mr. Griffith. But a year he waited for this study to get
off and running. Now, he was very happy, once it got started.
Let me switch gears a little bit on that, and we will stick
with you. When we are doing research on these types of
diseases, the neurodegenerative diseases, and we are trying to
recruit people from a wide variety of backgrounds, which I
understand, but one of the things that is probably an
impediment, which I know can be an impediment, is getting
people who are not located in the DC area up to NIH.
So what are you all doing to make sure that we have
participation from folks who live in rural areas, or maybe live
away from this area, and it is more difficult for them to
participate?
Dr. Koroshetz. Yes, well, that is a really good question.
And actually, the one bright side of COVID is that many of the
trials had to move towards remote visits with the patients. So,
again, you will talk to Merit about ALS trials later, but I
think they learned that they could actually do things remotely,
which is a tremendous advance for people who live far away,
people who have trouble coming into the centers to be enrolled
in trials.
NIH, actually, is in the very unusual position in which we
can use NIH funds to transport people from anywhere in the
country to NIH.
Mr. Griffith. Well, and I appreciate that, and that was
going to be one of my followup questions, is what can we do to
facilitate using more telehealth?
Because, you know, if it is a blood sample that needs to be
drawn, that can be done locally and then shipped to the NIH,
but I know you have to do some other things. And it may have to
be an occasional visit, but the more we can do with telehealth,
the better off all of our patients will be.
And again, I think I speak for both sides of the aisle and
this committee, we are anxious for agencies like yours to tell
us--what do you need put into language in the law so that we
can facilitate you all using more telehealth and making sure
that we are doing it right, so that we can get these studies
and get more participants in these studies. I do appreciate----
Dr. Koroshetz. I 100 percent agree, yes.
Mr. Griffith [continuing]. You all----
Dr. Koroshetz. One thing that might help, and we could talk
to Merit later, is helping physicians in one State be able to
work with patients in another State, without having to get a
license. I know when I did telehealth, I had to have 15
different medical licenses for each State I worked in. One
place----
Mr. Griffith. And we have done that in special
circumstances in the past. I will look into that. Thank you so
much for your testimony.
Thank you all for being with us today.
I yield back.
Dr. Koroshetz. Thank you.
Ms. Eshoo. The gentleman yields back.
I would just add that the bills that we recently approved
of with Mr. Hudson and myself, the additional funds for the--
you know, that will help too.
And I want to encourage all of the witnesses to share with
us up front what you need in order to make all of this work
better. Don't be shy about it. That is what these hearings
are--it is one of the important aspects of the hearing.
The Chair is now pleased to recognize the gentleman from
Maryland, Mr. Sarbanes, for his 5 minutes of questions.
Mr. Sarbanes. Thanks very much, Madam Chair, and I
appreciate the opportunity. I want to thank the panelists for
testifying today.
We have had others, I think, speak to this to some degree
already in the hearing. But I wanted to come back and talk
about the importance of inclusion and exclusion criteria that
are used by developers in determining who participates in these
various clinical trial studies.
In recent years, as you know, there has been a push to
diversify study participants to better represent the
populations that eventually may use an approved drug. The FDA
Reauthorization Act of 2017 required FDA to hold a public
meeting on clinical trial inclusion and exclusion criteria,
which was held on April 16th, 2018. A report was issued shortly
thereafter.
Putting these inclusion and exclusion guidance measures
together in a comprehensive way and into effect for terminal
neurodegenerative diseases can present unique challenges, as
you know. Researchers have to evaluate populations at different
phases of disease progression, which is complicated, and
determine how to maximize the clinical benefit that is brought
to bear at each stage.
As FDA noted in its report, there is a tension between
balancing the desire to minimize statistical noise, which can
mask a finding of the effect for a certain population, on the
one hand, and then the desire to generate data that can be
applied to a broad patient population, on the other hand.
Dr. Cavazzoni, can you summarize why this tension exists,
and what developers, in your view, should consider in order to
balance tension, especially when it comes to neurodegenerative
diseases, which we are discussing today?
Dr. Cavazzoni. Thank you for the question. I acknowledge
the fact that there is anxiety among developers in some
instances when it comes to broadening inclusion criteria in
clinical trials. These--inclusion of under-represented racial
and ethnic minorities, or inclusion of some subset of the
population that are affected with the disease, such as we heard
earlier, Down syndrome and Alzheimer's.
We think that we can--developers can find ways to
appropriately represent the subgroups that are affected by the
disease while also be able to conduct clinical trials in a
timely fashion without seeing those clinical trials slow down.
And in addition to the guidance that we have issued, when
we meet with developers we talk about tactics, such as having
in place the appropriate outreach to a certain geographic area
or establishing a network of treating physicians who may be
able to refer clinical trial participants and--as well as, you
know, making sure that we deploy--to the earlier conversation--
important tools, such as decentralized clinical trials.
And we have issued guidance on decentralized clinical
trials during COVID, and we are working on a go-forward
guidance, recognizing that one of the reasons for--some
subpopulations that have been underrepresented in clinical
trials, cannot access clinical trials, it is because they
cannot travel there, as we have just heard. They live in rural
areas and so on. And therefore, it is particularly important
that we encourage developers to use decentralized modalities,
including telehealth, digital health technology, as a way to
capture endpoints in a way that doesn't require people who
suffer from neurodegenerative diseases--so maybe on a
wheelchair and debilitated--to travel to an investigative site,
but rather, have those procedures done remotely, using
telehealth when possible.
And so we think that we can get to a point where we can
have greater representation, and appropriate representation, of
all the subgroups while not slowing down the drug development
and the timing of clinical trials.
Mr. Sarbanes. Thank you very much, I appreciate your
testimony.
I yield back.
Ms. Eshoo. The gentleman yields back. The Chair is pleased
to recognize the gentleman from Florida, Mr.--I am sorry--
Bilirakis for his 5 minutes of questions.
Mr. Bilirakis. Thank you, Madam Chair. I appreciate it very
much. I thank you for holding this hearing, a very important
hearing. I give thanks for holding the hearing, so we can learn
more about the challenges involved with these neurodegenerative
diseases, such as ALS, which is a brutal disease that, sadly,
has no known cure or any real treatment.
I was particularly saddened to learn this past week of the
passing of my constituent and good friend Doug McGinnis, a
combat veteran who was diagnosed with ALS over 15 years ago. He
was an incredible lawyer, Madam Chair--I knew him very well--
and managed to fight back for many years before the disease
again progressed. Unfortunately, since he received experimental
treatments--and that prolonged his lifetime--from outside of
the United States, he was barred from clinical trials here in
the U.S., and ultimately he couldn't access the treatments that
were effective for him, sadly.
Both he, his wife, and my good friend--and also a
constituent--Gary Desati, has been at the forefront of the
critical fight against this disease. And I agree we must act
and do more.
So my question is for Dr. Cavazzoni--I am sorry--Cavazzoni.
We have heard and will hear the concerns from the ALS community
that the heterogeneity and rareness of the disease and others,
such as Huntington's disease, can complicate participation in
clinical trials and access to investigational therapies.
In Doug's case, these included adult stem cell treatments
that proved effective for him, in particular. Again, he had
several treatments outside the United States.
How can we better improve the drug development process so
that patients with varying stages of neurodegenerative diseases
are able to participate in clinical trials?
Dr. Cavazzoni. Thank you for the question. And first, let
me say how sorry I am about the passing of your constituent
after a battle with ALS.
Mr. Bilirakis. Thank you.
Dr. Cavazzoni. I am very sad to hear that.
When it comes to the ability to access drugs, despite the
heterogeneity of diseases, ALS is a good example of a rare
disease where we know that there are certain forms that are
genetic and where we have actually been able to underpin the
genetic mutation that then allows for development of very
targeted drugs.
On the other hand, the 90 percent, or 85 to 90 percent, of
ALS is actually sporadic, meaning that we have not identified a
specific genetic mutation or molecular underpinning, and that
poses some challenges when it comes to development.
On the other hand, the way we have continued to advance the
development, even if we--in many instances in these diseases we
do not have a full understanding of the biology--is to work
with developers and with the disease community, who identified
modalities that can still allow patients to be evaluated in
clinical trials.
For instance, going back to the work that we have done with
ALS and the guidance, we have identified a host of clinical
endpoints that, even without an understanding of the molecular
biology of the disease or having biomarkers, can allow us to
adequately and quickly evaluate a drug and determine whether it
can be advanced, and whether the benefits and risk profile is
positive. And these tools for ALS include--or these endpoints
include endpoints such as function, breathing--tracheotomy,
muscle strength, and so on, because we really want to make sure
that developers can use multiple approaches to evaluating these
potential therapeutics.
Mr. Bilirakis. Madam Chair, I have a question with regard
to Parkinson's disease and Alzheimer's, but I know we don't
have a lot of time, so I will have to submit them for the
record. Thank you very much, I appreciate it.
Ms. Eshoo. I thank the gentleman for his questions. And do
submit your written questions to our witnesses.
The Chair now is pleased to recognize the gentleman from
Vermont, Mr. Welch, for his 5 minutes of questions.
Mr. Welch. Thank you very much, Madam Chair. I want to ask
about three areas: one are migraines and headaches; two is ALS;
and three, Alzheimer's.
Director Koroshetz, oftentimes we talk about headaches, and
it is way, way worse than that. Nearly 50 million Americans, as
you know, suffer from migraines. Forty-six of my colleagues,
bipartisan, have written to the--in support of the HEAL Act.
My question to you is, could you tell me what the NIH is
doing to help the millions of Americans who are suffering from
headache disorders?
And how can the NIH work to engage more researchers in this
field, considering the incredible impact on so many Americans?
Thank you.
Dr. Koroshetz. Thanks for the question. Yes, headache is
the leading cause of missed work in the U.S. It causes a lot of
suffering. We fund research trying to get at mechanisms by
which the headaches occur, and we have had some amazing
successes. So, you know, in my career, you know, there weren't
very effective drugs. Now we have triptans and the new drugs,
the CGRP antagonist, which came out of research on the
connection between the nerves and the blood vessels.
Industry has been really good at picking up on any kind of
discoveries that come out of science. And so the Lundbeck Prize
in neuroscience actually went to the three people who
discovered this CGRP mechanism.
Now, truth of the matter is, in clinical practice we do
have a great shortage of people who concentrate in pain and
headache. It is a very difficult field to go into.
Unfortunately, we have fewer people than we need. And the HEAL
initiative, which is--has a focus on building nonaddictive pain
therapies, has a lot of programs out now to do research,
including on headache, and to build new research capacity,
younger people, headache pain, any types of pains.
Mr. Welch. Thank you very, very much.
Director Cavazzoni, could you explain the actions that the
FDA has taken to expedite development and approval programs
available to bring new treatments to ALS patients as quickly as
possible?
Dr. Cavazzoni. Thank you for the question. We have been
working closely with developers to advise them on how to design
clinical trials, and--including identifying endpoints for
clinical trials, how to recruit for clinical trials in a way
that allows those trials to deliver answers as quickly as
possible, depending on the endpoint.
And so we are very engaged with developers, as we always
are, in--particularly when it comes to development of
therapeutics, where there is a large, unmet medical need. And
we guide them on the, really, the details on the clinical
trials, the endpoints that it could be using that may yield
faster answers.
And I am going to give an example of ALS. While we know
that clinical programs have been looking at the impact on a
potential therapeutic survival, we have heard from people
suffering from ALS that what matters to them is also
improvement in symptoms, improvement in quality of life. And so
we work with developers to really identify an array of ways to
evaluate the drug that could really yield the answers that we
know are meaningful to people suffering from the disorder.
Mr. Welch. Well, thank you both very much. I so appreciate
the work you are doing and your organizations are doing. I want
to end by just making a comment.
You know, Alzheimer's is just devastating. The drug
Aduhelm--there is a lot of controversy about the approval, but
the price is unreal. I just want to say this, because we get a
drug, and let's hope it works, but if it is so priced that you
can't afford it--and this one is--the pricing power that Biogen
had, they set the price at $55,000. There's 6 million Medicare-
eligible people who suffer from Alzheimer's. If just one-third
of those folks on Medicare took that drug, it would cost $110
billion, and that is more than the Medicare Part B program
spends on all medications for all patients.
So I really appreciate the work you are doing on research,
but we have to have reasonable pricing so it is affordable for
individuals, taxpayers, and for--and I yield back. Thank you.
Ms. Eshoo. The gentleman yields back. Seeing no Republicans
available for questioning, or committee Democrats, I will
recognize the gentlewoman from Illinois, Ms. Kelly, for 5
minutes of questions, and then make some remarks about
impending----
Mr. Cardenas. Madam Chair, this is Cardenas.
Ms. Eshoo [continuing]. Votes that we have.
Ms. Kelly. Thank you, Chairwoman Eshoo----
Ms. Eshoo. Oh, I am sorry. I think that--Robin, I think we
need to go to Mr. Cardenas for 5 minutes, and then let's see if
we can squeeze you in, as well.
The gentleman from California is recognized for 5 minutes
of questions.
Mr. Cardenas. Sorry about that, Madam Chairwoman, and I
could see myself on the screen, but I--maybe it wasn't
connecting to the committee. Thank you so much----
Ms. Eshoo. There you are, there----
Mr. Cardenas. I appreciate----
Ms. Eshoo. There you are.
Mr. Cardenas. OK. I appreciate this opportunity. Thank you
to all the panelists for your expertise and your advice that
you are informing us today.
I would like to cover various issues when it comes to
clinical trials, for example. Outside of the inclusion/
exclusion eligibility criteria, a number of external factors
may preclude individuals from participating in clinical trials.
These can include geographical limitations, financial burdens,
transportation difficulties, and the ability for caregivers to
assist patients in enrolling in a trial and participating.
In our second panel today we will hear testimony from a
witness who has--who was faced with all of these issues. One of
our witnesses, Yvonne Latty, describes in her written testimony
that she had to help her mother with Alzheimer's disease
commute from the Bronx to Manhattan every week while she
maintained a full-time job. To top it off, the clinical trial
barely compensated participants enough to cover the cost of a
cab from her mother's home to the research site.
As Ms. Latty notes, these issues are systemic, and the
Federal--and federally funded Alzheimer's disease research
centers tend to be in the wealthiest neighborhoods, to add
insult to injury, for people who would love to be part of these
trials but live on the other side of town. And it is clear
that, if we are going to discover new treatments that are
available to the widest possible patient population, we need to
do more to break down these barriers and expand access to
clinical trials.
Dr. Cavazzoni, what guidance has the FDA provided to
developers in how they should consider these nonclinical
barriers, including financial barriers?
Dr. Cavazzoni. This is an area where we are putting a lot
of thought, and we are putting a lot of work into this because
we recognize that it is critical to increasing the
representation of underserved communities and underrepresented
racial and ethnic subgroups.
During COVID we very quickly issued guidance on how
developers could use decentralized clinical trial approaches to
make it easier for patients to participate in clinical trials
or stay in clinical trials during the pandemic. And those
modalities entail using technology, telehealth, digital health
tools, and also include encouraging developers to design
clinical trials in a way that they are as simple as possible,
that don't require multiple unnecessary visits, such as the
situation, you know, that can be very cumbersome, as you
described in the caregiver who was--had to go to a--through the
Bronx----
Mr. Cardenas. Thank you, Doctor. My time is limited. I
would like to get a question in to Dr. Hodes. Thank you so
much.
The ability of a caregiver to assist the patient and
accessing a clinical trial can be critical, especially for
older adults and those with Alzheimer's disease, for example.
Has NIH evaluated the role that caregivers play in facilitating
patient access to trials, and what can be done to support
caregivers so more patients can participate?
Dr. Hodes. Thank you for the question. You know,
absolutely, in many--certainly Alzheimer's, as disease
progresses it is critical that there be provision made for a
caregiver or someone to accompany the person living with
dementia. And this is a part of the study, it is a part of the
design, it is a part of what we can fund.
Your point well taken, too, though, about outreach, and
doing our best--sites located as close as possible to affected
communities. To that extent, we have established a standing
infrastructure of clinical sites, so we don't have, for each
clinical trial, to redesign and reidentify those sites.
The use of remote--is another important area, as just
mentioned. And in some areas, at a national level, I recognize
we haven't had Alzheimer's disease research--in all parts of
the country where the disease is most prevalent. Just recently
we funded four pilot centers in previously unrepresented areas
in Nevada, New Mexico, Alabama, and Tennessee, all of these
designed to accomplish what you said, to try to put the
clinical science as close as possible to affected populations,
allow for companions when needed, and do as much as we can
remotely to reduce the burdens of participation in trials.
Mr. Cardenas. Thank you, and health equity is something
that is very important to every single person on this
committee, and I am sure it is on--it may not be on the minds
of every American, but I think that every American would agree
that everybody deserves not only equal access but also equal
care. So thank you so much, and I look forward to seeing you in
the future. And once again, thank you for being here today.
My time has expired. I yield back, Madam Chair.
Ms. Eshoo. The gentleman yields back. It is my
understanding that Dr. Ruiz is with us, and I recognize him for
5 minutes for his questions.
Mr. Ruiz. Thank you very much. Thank you for holding this
important hearing today.
As a physician and chair of the Congressional Hispanic
Caucus and the son of farmworkers who grew up and practiced
medicine in the medically underserved Coachella Valley area in
California, I am happy to hear so many Members talk about the
importance of diversity in clinical trials.
Factors such as gender, race, ethnicity, age, or lifestyle
play an important role in how our bodies respond to the
different medications and therapies. And what is more, the
disproportionate impact of the COVID-19 pandemic on communities
of color has highlighted the vital importance of including
diverse participation in clinical trials.
Addressing the social determinants of health and creating
greater health equity has long been one of the top priorities
of the Congressional Hispanic Caucus. And for the past several
months I have been working with fellow Hispanic Caucus member
Senator Menendez on important legislation aimed at improving
diversity and inclusion in clinical trials through supporting
patient engagement of communities of color in decentralized
clinical trials and developing solutions to better recruit
racially and ethnically diverse populations.
NIH and FDA's engagement will be key in improving outcomes
and the participation of communities of color in clinical
trials for neurodegenerative diseases and beyond. The first
question is to Dr. Cavazzoni.
How do you determine if the clinical trial data you receive
in the drug application is representative of the U.S.
population?
And when, if ever, do you require a sponsor to increase the
size of your clinical trials in order to accurately understand
if there are different outcomes and different demographic
groups?
Dr. Cavazzoni. So we have issued guidance to sponsors to
encourage them to make sure that the entry criteria for
clinical trials are as broad as possible and to encourage them
to ensure that there--the--there is representation of racial,
ethnic, and other subgroups that are relevant and represented
in that particular disease.
When we talk to sponsors about the design of clinical
trials, this is very much top of mind. And we discuss with
sponsors modalities and approaches to make sure that the
clinical trial population is as close as possible in
representing the scope of groups that suffer from the disease.
This is an area that is very important to us. We have made
gains over the past few years, as shown in the clinical trial
snapshot that we published a while ago. And we----
Mr. Ruiz. Thank you.
Dr. Cavazzoni [continuing]. Understand that we need to
continue to focus.
Mr. Ruiz. Thank you, thank you.
Dr. Cavazzoni. Sorry.
Mr. Ruiz. Given the nature of neurodegenerative diseases,
how can greater use of decentralized clinical trials improve
the experience for all patients and make trial participation
more accessible for more diverse communities?
Dr. Cavazzoni. So we think that using decentralized trial
approaches can be really important tools in facilitating the
participation and the inclusion of patients, particularly
patients in underserved communities, in neuroscience and
neurodegenerative diseases, particularly in diseases that are
debilitating, such as the ones that we are discussing, that are
dependent on caregivers going with the patient to a clinic or a
clinical site. We think that these decentralized modalities
that use telehealth, that simplify clinical trials, that make
it easier to collect data from the patient's home or for, let's
say, a lab technician to go to the patient's home to collect
the blood test----
Mr. Ruiz. Thank you.
Dr. Cavazzoni [continuing]. They are critical in ensuring--
--
Mr. Ruiz. Thank you. I have 40 seconds left.
I would like to ask Dr. Hodes from NIH what your
perspective on--in terms of the importance of diverse
participation for those therapies being developed for
neurodegenerative diseases, and what you think about improved
community outreach to diverse--to increase diverse
participation in those clinical trials.
Dr. Hodes. So hugely important, not just for all of the
moral and ethical principles, but because we already know risk
factors differ across parts of our population. The Alzheimer's
disease itself is heterogeneous. So, for example,
cardiovascular and other contributions will--an absolute
imperative.
I see time running, but as far as outreach, the new
technologies will help. So, rather than the current situation,
where we may have to bring people into a site that has access
to a PET scan, we have the ability to use blood biomarkers to--
takes one of our restrictions and constraints away.
We also put into place a system in real time for tracking
each individual accruing to a study for ethnic, demographic
characteristics, so we can track not just on an annual report
but in real time and see if we are on track in each study, and
the collection of those studies, in meeting the goals.
Ms. Eshoo. The gentleman's time has expired.
Colleagues, we are going to--and witnesses, we are now
going to break, because we have seven bills on the floor that
we have to vote on. So we will take a recess. I think that we
will come back at--well, we will take Robin.
Let me just make this announcement. We will take Robin
Kelly, and then we will recess, coming back at approximately
3:30, 15 minutes after the last vote is taken. Hopefully, votes
will end sooner than that. So I encourage Members and witnesses
to return in a timely way.
We will take one more Member, Congresswoman Robin Kelly,
and then we will recess. I think everyone needs a break,
anyway. So the gentlewoman from Illinois has 5 minutes for her
questions, and then we will take our break.
Ms. Kelly. Thank you so much, Chairwoman Eshoo, and Ranking
Member Guthrie. I really wanted to talk about clinical trials,
and, you know, there is always a concern about how they reflect
the diversity of our population. So we need to ensure that
clinical trials are reflective of the racial disparities in
neurodegenerative diseases.
According to the ALS Association, Black patients are 2.5
years younger than White patients at the time of symptom onset
and are up to 1 year delayed in receiving an ALS diagnosis.
This is one of the many stats that highlight the need for
increased diversity in clinical trials.
Dr. Koroshetz, what guidance has NIH provided to sponsors
to ensure that demographic diversity in clinical trials is
reflective--excuse me--of disease disparities, including race,
ethnicity, and gender?
Dr. Koroshetz. Thanks a lot. So at NIH, the trials that we
run, we are obliged to report what the population is on a
yearly basis, and we examine those. And if it has fallen short,
we put in, you know, changes to improve the diversity of the
participants.
We also find--particularly relevant here--there is actually
research to try to understand what is the best way of detecting
these conditions in different populations, because, as you
mentioned, there is a problem there. And as these treatments
come along, the worst thing you want is for the diagnosis to be
delayed, because the treatment is going to be best early on.
So we do something called--there is a program called Detect
Cognitive Impairment, which is to try and figure out how to
know when someone is developing these neurodegenerative
diseases. And that is done in many different populations, for
the exact purpose that you raised.
Ms. Kelly. Would there be any additional benefit to having
sponsors work with NIH to establish clear, measurable diversity
goals in the funding application and to have those goals be
publicly available and enforced throughout the trial?
Dr. Koroshetz. You know, I--well, my understanding is that
NIH--we do what we have to do, and we do what you say, but we
don't have any--I don't know that we have any leverage on what
the industry folks do.
I mean, that--the FDA might be able to say what their
levers are in that space, but we don't have any levers there.
Ms. Kelly. But we do need to improve the clinical trial and
drug approval process----
Dr. Koroshetz. Yes.
Ms. Kelly [continuing]. Continuing to fund basic research
to understand how these devastating brain diseases work. This
will ensure that we have a continuous pipeline of novel
therapies.
Dr. Hodes, what are some promising areas of research for
neurodegenerative diseases, and how can we increase the
likelihood that this research translates to novel therapies?
Dr. Hodes. Well, for Alzheimer's disease, in particular, as
noted, we have come in the last few years to recognize that
there are multiple pathways on a molecular, cellular level,
that contribute to Alzheimer's as a clinical syndrome. And we
have made great progress in translating that basic information
already into clinical trials that target components of them. So
in some individuals it may be that the vascular component is
dominant. In others, it may be an inflammatory component. In
others, errors in folding of proteins.
And so, ranging from drugs, to small molecules, to
individual and combination behavioral therapies, as is
necessary in diseases as complex and devastating such as this,
we are targeting multiple such pathways with the notion that--a
personalized or precision level, we are going to find
differences not just in racial [audio malfunction] individuals
in designing the optimal therapy.
Ms. Kelly. Thank you so much, and I will yield back the
balance of my time. Thank you.
Ms. Eshoo. The gentlewoman yields back. The Chair will now
recess the committee, and resume at approximately 3:30 this
afternoon.
[Recess.]
Ms. Eshoo .[In progress] resume and be back in order. To
all the witnesses, to say I apologize on behalf of all of the
committee, subcommittee members, and myself really doesn't
begin to describe it.
I just leaned over and said to the ranking member that I
have learned something. The week that precedes heading into a
major break, I don't think I will ever schedule a hearing
again, because we have absolutely no control over what is going
to take place on the floor.
So apologies to everyone, especially our witnesses that
have flown across the country to be in the room to testify, and
sitting in a wheelchair, waiting. I just--I--you know, our
deepest apologies.
So now, back to where we left off, it is--the Chair now has
the pleasure of recognizing the gentleman from Oklahoma, Mr.
Mullin, for his 5 minutes of questions.
He is not ready? All right, all right. Then we will go to
Dr. Joyce.
He is? He needs to--Mr. Mullin, you need to unmute. I can't
hear.
I think that we will go to the gentleman from Pennsylvania,
Dr. Joyce, for your 5 minutes, sir.
Mr. Joyce. Thank you for yielding, Madam Chair, and to this
panel of witnesses, your testimony today, on a long day, but an
incredibly important issue.
Neurodegenerative diseases devastate the lives of those
diagnosed. It impacts their family members and all around them.
It is critical that we are putting forward the proper set of
policies that will foster the research and the development of
cutting-edge therapeutics and cures that will stall these
diseases. We need to have that impact. My first question is for
Dr. Cavazzoni.
My home State of Pennsylvania has been a global pioneer in
the fields of cell- and gene-based therapies, which could offer
incredible help to patients with neurodegenerative diseases.
Does the FDA have the necessary resources and the necessary
workforce expertise to ensure timely review and approval of
these new medicines for years to come?
Dr. Cavazzoni. Thank you for that question, and I will
assume that you would like me to comment broadly on cell and
gene therapies and not specifically for neurodegenerative
diseases, although I am certainly happy to touch on that.
So this area is an area that is really exploding, when it
comes to research and a number of programs that are coming to
the FDA for review. And the review is done not by my center,
but the Center of Biologics. And so, certainly, this is an area
where we need to continue to be able to invest in a highly
specialized workforce that will allow us to keep pace with both
the volume and the scientific advances that we see in cell and
gene therapy.
Understanding that this area is also particularly important
for advancing new therapies for neurodegenerative diseases, and
in order to do so, we will need resources, as well as--we will
need to be able to recruit the right scientists and personnel
and experts and, you know, be competitive with the private
sector.
And to this I would like to really extend--acknowledge the
tremendous support by Congress by passing the--by giving us the
H.R. Cures authorities, which is the hiring authority that
really allows us to be much more speedy and competitive with
the private sector in recruiting highly specialized scientists,
such as the ones that we need to review applications, and work
with sponsors who are developing therapeutics in gene and cell
therapy.
Mr. Joyce. Dr. Cavazzoni, we are going to be hearing from
our second panel of witnesses that the FDA has not fulfilled
its commitments to provide regulatory flexibility or consider
patient tolerance for risk and the life-threatening nature of
diseases when making regulatory decisions about drugs to treat
ALS, as outlined in the agency's September 2019 guidance for
ALS clinical trials. What is your response to this?
Dr. Cavazzoni. Thank you for the question. I think it is
important to differentiate the--how the fact that we are, in
fact, operating in a manner that is entirely consistent with
the ALS guidance that we have put in place when it comes to
what we ask, and--the sponsors to do, as they develop clinical
trials and design clinical trials and conduct them.
Now, that guidance is really about how to develop drugs for
ALS. However, at the end of the day, our decisions are based on
the data that are derived from those clinical trials. And
sometimes----
Mr. Joyce. With our remaining time, do you feel that
guidance is necessary, and is it reliable? Because I can't wait
to hear the patients comment on this.
Dr. Cavazzoni. We think that the guidance is very important
for developers. At the end of the day, we have to make
decisions on the basis of the strength of the data that is
derived from those developments and those clinical trials that
may well have been designed in complete compliance and
according to the guidance. However, sometimes we are
disappointed by what the clinical trials give us in terms of
results, and we are left with data that are sometimes either
very complex to understand or sometimes insufficient for us to
make a determination that the drug can be approved.
Mr. Joyce. My time has expired. Thank you, Madam Chair. I
yield.
Ms. Eshoo. The gentleman yields back. The Chair now
recognizes the gentleman from Oklahoma, Mr. Mullin, followed by
the gentleman from Utah, Mr. Curtis. And I am taking two
Republicans in order, because Ms. Schakowsky is waiving on to
the committee.
So we will hear from both of you first. So, Mr. Curtis, you
are recognized.
Mr. Mullin. Mullin, Mr. Mullin.
Ms. Eshoo. Oh, I am sorry, Mr. Mullin.
Mr. Mullin. Yes, I am not letting John get in front of me.
He always cuts.
Ms. Eshoo. Are you all miked up?
Mr. Mullin. Yes, I am ready to go.
Ms. Eshoo. All right.
Mr. Mullin. All right, thank you so much, Madam Chair, and
thank you for our witnesses that are here. I just wanted to
throw out some questions to Dr. Cavazzoni.
There are numerous documents from the FBI that discusses
the importance of exercising regulatory flexibility when it
comes to approval for ALS therapies. Has--how has the FDI--FDA
exercised----
Ms. Eshoo. Mr. Mullin, excuse me, can you----
Mr. Mullin. Yes?
Ms. Eshoo. Mr. Mullin, excuse me, I am sorry. Can you speak
up? Because we are having a hard time hearing you, and we don't
want to miss a word.
Mr. Mullin. Oh, I am so sorry. Hold on.
Ms. Eshoo. OK.
Mr. Mullin. Is that better? Can you guys hear----
Ms. Eshoo. It is a little better. We want it even----
Mr. Mullin. Is that better?
Ms. Eshoo. Yes, just speak up.
Mr. Mullin. OK. I am turning my mike up all the way, is
that better?
Ms. Eshoo. OK.
Mr. Mullin. Can you hear me now?
Voice. We can hear you.
Ms. Eshoo. We can hear you, thank you.
Mr. Mullin. OK. There are numerous documents from the FDA
that discuss the importance of exercising regulatory
flexibility in the approval of ALS therapies. Do you know how
the FDA has exercised regulatory flexibility when it comes to
reviewing clinical trials with ALS?
Dr. Cavazzoni. Well, we exercise regulatory flexibility as
we review the data from all life-threatening diseases,
including ALS, and the--our ability to fully exercise
regulatory flexibility within the confines of, you know, our
statutory standards is--at the end of the day, is dependent on
the data that is in front of us, and what the clinical trial
results are telling us.
And so there are times when the--despite the fact that we
are very committed and very willing to be as flexible as we can
within our standards, the data are not sufficient for us to be
able to exercise the extent of regulatory flexibility that we
would want to be able to do in situations such as ALS, where
there is such a huge unmet medical need.
Mr. Mullin. There is--the issue that you have is we feel
like it is very possible that the drug will work well in some
ALS patients and not others, just kind of like chemotherapy
treatments work well for some cancer patients, and some others.
And what the fear is, is that we are sometimes waiting on
the FDA to have approvals, but yet the ALS patients are just
saying, ``Listen, we will try whatever.'' I mean, if it is
working on some patients, and even though it may not be working
on all patients, they are--the ability to try--we passed a bill
for pediatrics that said the right to try, to allow pediatric
cancer patients the right to try drugs that were available. And
I think that is what ALS patients are wanting too.
Dr. Cavazzoni. Well, these are very important points. I
think it is important to distinguish the access, the importance
to provide access to investigational therapies through expanded
access programs, or right to try, versus the importance of
being able to study drugs in controlled clinical trials----
Mr. Mullin. Sure.
Dr. Cavazzoni [continuing]. In a way that would allow us to
understand whether they work, and their--whether they are
sufficiently safe. And so we try to balance that need by
working with sponsors to put in place clinical trials that have
the best chance to be able to give us answers, including
answers about subpopulations within ALS. And I recognize and I
agree that this is a very heterogeneous disease, as many rare
diseases are.
And in parallel to that, we work with sponsors to
facilitate access to treatments through expanded access. And to
that effect, obviously, we try to do everything that we can to
facilitate those programs.
Mr. Mullin. Well, I have visited with some of my
constituents that have had--responded well to some of the ALS
treatments that they participated with, with clinical trials.
And then, you know, of course, some of them would love the
opportunity to do that.
And I just wonder if the FDA is doing other things to
ensure that treatments that are available to patients that they
have seen some success with are available to other patients
that would like to try it, because I know we have had several
reach out to us and say, ``Hey, we have spoke to constituent A,
and they have responded well on--in this trial, but we have
tried to get involved in the trial, and we are being denied.''
And I am just wondering if the FDA could be more flexible on
that.
Dr. Cavazzoni. Well, we try to be as flexible as we can
within the--our authorities. So, for instance, we work with
sponsors, and we encourage them to have open-label extensions
in their clinical trials after the controlled phase of the
trial has ended, so that all patients can move into that open-
label extension and have access to the drug.
And we also encourage sponsors to make the drug available
through expanded access after the trial is completed, or even
only after the controlled phase, the placebo controlled phase
of the trial is completed. Ultimately, we need the sponsors to
be willing to work with us. And, obviously, we engage them
regularly on these matters because we really understand the
tremendous urgency and unmet medical need.
Mr. Mullin. All right. Well, I am out of time. If
Congress--if we can be helpful to you in any way, if there is
any barrier that is in place that is keeping you from being
able to do that, let us know.
With that, I will yield back. Thank you, Madam Chair.
Ms. Eshoo. The gentleman yields back. The Chair is now
pleased to recognize the gentleman from Utah, Mr. Curtis.
Mr. Curtis. Thank you, Madam Chair, and I am pleased to be
here, and this is an important hearing. I think you are going
to hear in my questions a theme that we have heard throughout
the day. I would like to start with Dr. Cavazzoni.
My colleagues and constituents back home often communicate
to me that the FDA needs to be less risk-averse, and they cite
the inability to access tutorial treatments under expanded
access. A right to try is one reason why.
Now, I have here my notes, ``without undermining patient
safety,'' but I am going to put a big asterisk by that, because
our patients are not exactly worried about their safety, right?
They are worried about living. And so, with that in mind, is
there more that Congress can do to make the FDA and
pharmaceutical community more comfortable offering these drugs
to patients under expanded access and right to try?
It feels to me like there is some hesitancy because
patients might not always be in the best health. They may not
be the best clinical pick, but they are denied a potential for
something lifesaving because of this risk-averse nature. So my
question to you is what can Congress do to add to the comfort
level of both the FDA and the pharmaceutical companies, so they
are more willing to take more risk?
[Pause.]
Mr. Curtis. Dr. Cavazzoni, that is to you.
Dr. Cavazzoni. My apologies, Congressman----
Mr. Curtis. OK.
Dr. Cavazzoni. I did not unmute myself. When it comes to--
--
Mr. Curtis. I understand.
Dr. Cavazzoni. When it comes to clinical trials, we work
with sponsors who design clinical trials that have the best
chance of developing----
Mr. Curtis. So I am going to cut you off, Doctor, and I
don't mean to do that, but, you know, we have limited time.
That is really not my question.
My question is, these people are desperate for an
opportunity to try something, and there is an aversion to risk
on both the--and I understand that aversion, right? I mean,
that is natural. I mean, their reputations are at stake, the
reputation of the FDA is at stake. How do we protect, as
Congress, how do we protect them, so they are more willing to
take risk?
Dr. Cavazzoni. My--the--I would like to make the point
that, in fact, every day, when we work with sponsors and with
clinical trials for drugs for ALS, we take into consideration
the fact that there is a much higher tolerance for risk in
people who are afflicted by this disease, and we take that into
consideration as we review the data.
So, for instance, we do have a higher threshold when it
comes to safety. We also are open and have, in many instances,
accepted less safety information than we would normally
accept----
Mr. Curtis. Once again, I--and I just have so much I want
to ask you, so please excuse me for interrupting you. I really
would like you to go back and consider that question, because I
am--I just know that your nature, the nature of doctors, is to
not take risk. And I think we need a different paradigm here,
as we look at this.
Let me ask you again, and perhaps any of the witnesses that
would like to answer this. I have noticed and been touched by,
almost without exception, all of my colleagues who have asked
questions today know somebody back home, a family member, a
neighbor that is afflicted either by ALS or Down syndrome or
MS.
Of course, I am no different. ALS has ravaged my
neighborhood, and I currently have a very, very good friend
suffering from ALS. He has been fortunate, because of some of
his resources. He has been able to travel worldwide to receive
some of these treatments. So many are not. He frequently
discusses how patients are unable to receive many treatments
under right-to-try that are under clinical investigation for
which he can--if he is willing to travel, and spend more than
the average person is able to do--access.
I get it. The complexity of treating certain diseases can
be a challenge, especially to ensure sufficient trial
participation. Additionally, it is hard to predict how
individuals may react to an experimental drug.
Is there more we should consider doing to get patients into
clinical trials without undermining the integrity of the trials
and harming patients?
And I am referring specifically to Congress, right?
I know that you are doing your job. What can we do to
expedite this?
Dr. Cavazzoni. I think that having more--having a greater
push when it comes to understanding the biology of disease will
be very important in advancing the therapy for ALS.
Continuing to support us, as we continue to focus on
expanding the eligibility criteria for clinical trials, will be
very important because we want to have as many patients as
possible being able to access clinical trials.
And also, continuing to support us in our efforts to engage
with sponsors to make drugs through expanded access more
available to patients----
Mr. Curtis. Thank you. Yes, Doctor, I am going to----
Dr. Cavazzoni [continuing]. Be very important.
Mr. Curtis. Please, I am going to lose my time. I want to
make one point, and that is something that you brought up,
which is cause. We spend a lot of time and we have talked a lot
time today about treatment. But I am not convinced that we
exactly know the cause--if it is environmental, if it is not
environmental--and I would just like to emphasize how important
your work is in that area.
Thank you, Madam Chair, I yield my time.
Ms. Eshoo. The gentleman yields back. The Chair is now
pleased to recognize the gentlewoman from Delaware, Ms. Blunt
Rochester, for 5 minutes for her questions.
Ms. Blunt Rochester. Thank you, Madam Chairwoman and
Ranking Member Guthrie. And thank you to the distinguished
panel before us today on neurodegenerative diseases.
As was said by Mr. Curtis, almost all of us in this hearing
have been personally touched. I lost a friend and also a loved
one to ALS. I had a grandmother and great-grandmother who
suffered from dementia and recently a longtime neighbor who
died from Alzheimer's disease, and I have seen firsthand the
devastating impacts these diseases have on our loved ones and
the toll that they take on our working families.
As you all have noted, Black Americans are about 2 times
more likely and Latinos 1.5 times more likely to develop
Alzheimer's than non-Latino White Americans. At the rate we are
going, by 2030 nearly 40 percent of all Americans living with
Alzheimer's will be Latino or Black. Black and Latino Americans
living with dementia are also less likely to receive a timely
diagnosis, more likely to report experiencing racial
discrimination along their patient journeys, and less likely to
be enrolled in cutting-edge Alzheimer's and brain health
research.
I want to highlight this last point because I think it is
important. Latino and Black Americans make up less than 10
percent of all clinical trial participants in active
Alzheimer's research. And, as I just mentioned, in less than 10
years 40 percent of Americans living with Alzheimer's will be
Latino or Black.
This is why I introduced a bipartisan bill with my
colleague Congresswoman Herrera Beutler, H.R. 3085, the ENACT
Act, to increase the participation of these underrepresented
populations in Alzheimer's and other dementia clinical trials
by expanding education and outreach to these populations,
encouraging the diversity of clinical trial staff, and reducing
participation burden.
Dr. Hodes, I am grateful for the technical assistance that
your team has provided on my bill, the ENACT Act, and I look
forward to our continued collaboration. As you know, the
National Institute of Aging currently funds 31 Alzheimer's
Disease Research Centers at major medical institutions across
the United States. However, an analysis has shown that the
geographic distribution of the nation's 31 federally funded
ADRCs skews toward the most wealthy neighborhoods. Would you
agree with that characterization?
Dr. Hodes. Let me agree with the extreme importance of what
you said, including diverse--in our trials, and doing what we
can to make that happen. And the location and sites for the
trials is critically important, I agree. I had mentioned
earlier in this hearing that, even at the gross level--the
States, large regions where we do not have Alzheimer's Centers,
and we have corrected that, in addition--four States in this
past year, to try to extend.
You are right. Because the academic research centers are
often situated in major cities, this leads to the unintended
but serious consequence of limiting to those people who have
direct access to the studies there. We are working very hard to
get around that, and newer technologies are helping. For
example, remote contact with individuals for assessment of
cognition. Looking forward to the day when we can replace the
PET scans, which have to be done at centers which can make the
radioisotopes, with blood tests which will extend what we do.
Putting registries in place--we track for every study, not
just by an annual report but essentially real time, how many
people were recruited in each study, what their demographics
are, and rapidly turn around to correct things if those are not
living up to standards.
But with your help, as well, increasing the visibility in
communities to help us in recruiting for studies individuals
who are--who mirror the population, including those, as you
noted, who are at the highest risk of all.
Grossly unsatisfactory, currently. These are among the
things we are doing, with help of you and others, to help make
this difference in the immediate future.
Ms. Blunt Rochester. Yes, one of the things that our bill
would do is actually increase the number of ADRCs in areas with
higher concentrations at places like historically Black
colleges and universities, Hispanic-serving institutions,
Tribal colleges, and other underrepresented populations. And so
further, our bill would provide funding so that the new
research centers could establish and operate diagnostic and
treatment clinics, which we believe are important.
Do you believe that funded research centers with clinics in
areas with higher concentrations of minority groups could help
them to better connect with diverse population and enhance
recruitment?
Dr. Hodes. Well, I mean, we certainly are looking for ways
to do just that, to--local contact with individuals, more local
access to research, studies, and trials, absolutely.
Ms. Blunt Rochester. My last question, I have run out of
time. We will follow up with you, but I wanted to ask
specifically about how we can improve engagement with
underrepresented populations in research and some of the things
that you believe are necessary to do that. So we will follow up
with you in writing, and thank you.
I yield back, Madam Chair.
Ms. Eshoo. The gentlewoman yields back. The Chair is now
pleased to recognize the gentleman from Texas, Mr. Crenshaw,
for his 5 minutes of questions.
[Pause.]
Ms. Eshoo. Mr. Crenshaw, you need to unmute.
[Pause.]
Ms. Eshoo. All right, I----
Mr. Crenshaw. Does that work now?
Ms. Eshoo. Yes, there you are.
Mr. Crenshaw. OK.
Ms. Eshoo. Yes, I can hear you----
Mr. Crenshaw. Sorry about that, thank you. Thank you, Madam
Chair----
Ms. Eshoo. You can proceed, please.
Mr. Crenshaw [continuing]. Thank you, Dr. Cavazzoni, for
being here with us.
I want to ask you, when you make determinations on drug
approvals and emergency authorizations, would you ever use data
or studies that have been rejected in peer review?
Dr. Cavazzoni. If I understand your question correctly, you
are referring to peer review in clinical journals. And when we
look at the data and consideration about approval, we look at
the totality of the data that is presented to us. So we don't
necessarily exclude data on the basis of where they were
published or whether they were published, the data provided to
us by the sponsor. And we also look at everything else that we
can find in the public arena, including published journals----
Mr. Crenshaw. Sure. I mean, this isn't a trick question,
honestly. I don't think the FDA has relied on large decisions
and relied on a single study that has been rejected in peer
review, right? I doubt the FDA has done that. It is not a trick
question.
Dr. Cavazzoni. Well, I don't take it as such, Congressman.
I cannot think of an instance where this may or may not have
played out in our deliberation. The point that I was trying to
make is that we look at all of the data that is presented to
us, and whether it has been published or not is----
Mr. Crenshaw. I appreciate that. I appreciate that. Let me
move on. I have got to make a point, because it is big in
current events right now, that the CDC is using a study that
was rejected in peer review in trying to justify their new
mandates. The CDC cited a study that was rejected and only
included symptomatic patients and evaluated a vaccine,
AstraZeneca, that is not allowed for use inside the--in the
U.S.
The FDA, where you come from, has supported data that shows
that the COVID vaccines that we approved here in the United
States prevent transmission and are effective against the Delta
variant. Is that still true?
You know, you are just--you are from the FDA. And so that
is, you know--you are the only person we have here, so that is
why I am asking.
Dr. Cavazzoni. Yes, I didn't come prepared to speak to
vaccines today. And we have a whole center that----
Mr. Crenshaw. OK, OK.
Dr. Cavazzoni [continuing]. Is focusing on that----
Mr. Crenshaw. OK, but you have--this is very much in the
public sphere. You have had conversations about this with CBER,
right?
Dr. Cavazzoni. I would be very happy to have our colleagues
at CBER and vaccine experts follow up with you and answer your
questions in writing. I would prefer to have the experts
address your very important question.
Mr. Crenshaw. You are a physician from the FDA, I consider
you an expert.
Let's move on. The FDA is also responsible for moving
forward with incredible, innovative work, especially from our
biotech community in Houston. And amongst these innovators are
stem cell therapies. And I think that is a--that is pretty
relevant for the current conversation about neurodegenerative
diseases.
And we have seen, in specific cases in Houston, where we
have been able to move regenerative cell stem therapies under
the RMAT pathway laid out by Cures, passed by this committee.
We are finding that the work is being stymied by some of the
unintended regulatory burdens surrounding the current RMAT
pathway. And I understand that you don't manage that division
directly, but, since I have you, don't you think--can you at
least say this, that autologous stem cell treatments can
provide a significant therapeutic benefit?
Dr. Cavazzoni. The stem cell treatments are part of an
array of potential therapeutic modalities. And ultimately,
whether they can be helpful or not depends on the data that is
generated by the clinical trials and the studies that look at
these therapies.
And so, you know----
Mr. Crenshaw. Well, you know----
Dr. Cavazzoni. I certainly do not----
Mr. Crenshaw. Well, I am kind of philosophical. I know you
are going to hedge, and you are going to--one philosophical
question that I think we would really like to address here is
the purpose--the mandate, the purpose of the FDA. Is it focused
on safety?
I think you can standardize safety pretty well. I think the
FDA focuses on that pretty well. But are you doing that at--but
are you also focusing on efficacy to such an extent that you
can't really standardize it?
With something like stem cell therapy, which is very
clearly safe, is the FDA getting in the way of it, trying to
standardize the efficacy of it in a very unreasonable way?
Is it--was it worth looking at a paradigm shift on that?
Dr. Cavazzoni. When it comes to diseases with unmet medical
needs, we take an approach where we want to be as flexible as
possible, understanding that there is a higher tolerance for
safety.
And we also--in a situation like when we use accelerated
approval, for instance, we also accept, when in the appropriate
instances, the fact that there may be some residual uncertainty
about efficacy, and this is actually an inherent element of the
accelerated approval pathway, which we have used in many
situations and--for unmet medical needs, such as, for instance,
oncology, rare diseases, and infectious diseases.
Mr. Crenshaw. OK, thank you. I yield back.
Ms. Eshoo. The gentleman yields back. The Chair is pleased
to recognize the gentlewoman from Washington State, Dr.
Schrier, for 5 minutes for her questions.
Ms. Schrier. Thank you, Madam Chair, and thank you so much
to the panelists for coming today, and also for your patience
with our crazy schedule today.
Neurologic diseases impact our communities and our
families. And I am so glad to know--relieved to know--that so
much research is happening in our institutions to find cures
and treatments for these sometimes really devastating diseases.
My State of Washington also houses some research
powerhouses in this space, from what we call ISCRM, the
Institute for Stem Cell Regenerative Medicine at the University
of Washington, working on stem cells and neurological
disorders, to the Paul Allen Institute, which was just awarded
a $40 million NIA grant to define the human brain's
vulnerability to aging and degeneration at the cellular level,
in partnership with UDaB and Kaiser.
Now, this week I read an NPR article highlighting some
similarities between long COVID symptoms and those of early
Alzheimer's, and raising the question about whether there could
be a common pathway. For example, genetic studies, evidently,
are showing that some of the same genes that increase a
person's risk for getting severe COVID-19 are also associated
with an increased risk of developing Alzheimer's. And this is
incredibly scary, partly because long COVID affects young
people, including children, and also because we are already
seeing this explosion of Alzheimer's cases in the baby boomer
generation. And to add to that would just be devastating for
patients and families.
So Dr. Koroshetz, I was wondering if you could tell me if
we know, you know, anything more about this. Can you enlighten
us a little bit with any more research into this space and
maybe applicability for children and whether we see these kinds
of manifestations in children with long COVID?
Dr. Koroshetz. OK, well, it is definitely an important
question, and we hope to get data coming in from what we call
the RECOVER study, which Congress has appropriated funds for us
to--we are going to be studying tens of thousands of people who
had COVID and try and understand what these persistent symptoms
really are, including children, pregnant women, people from
diverse backgrounds. So we are going to have more information.
We know very little now.
I would say that the cognitive problems that people with
persistent symptoms have are different than what you would see
in Alzheimer's disease. They are much more like what you would
experience if you had the flu and, you know, you just can't
think right, or you had a concussion. It is more that kind of
attention/concentration issues.
There is one study where they looked at the risk of
dementia in, you know, millions of healthcare records, and they
do see an increase that they think may be related to COVID. The
question there--and Dr. Hodes may opine--is whether or not
people who are having trouble, whether COVID could have tipped
them in a little bit further into the dementia/Alzheimer
process. But I think that is still a hypothesis.
Ms. Schrier. Yes, of course. Everything about this virus is
so new. Thank you for that.
And rather than hypothesizing, I am going to hop, just
because of timing, to my next question. I am going to pivot
again to children.
As a pediatrician, I interface most often in the neurologic
space with autism and with seizure disorders. And I was just
wondering--I will give this to you, as well, Dr. Koroshetz--if
you could just touch on the state of research into pediatric
neurologic diseases, specifically etiologies, causes of autism,
if we have any more information there, and also any new
treatments for epilepsy.
Dr. Koroshetz. Right. Well, I guess a lot to unpack there,
but I would say that what we have learned from the genetic
studies is that there is an overlap between autism and
epilepsy, very commonly, and also with developmental delay. And
so that is getting at kind of what are the problems that occur
as the brain is developing in a young child or even in a fetus.
And we have some clues. And the question is how to go from
those genetic clues to treatments.
I would say, in the epilepsy space, there are some very new
genomic techniques that are now coming out, because we know
what the different mutations are, and they are very mutation-
specific. So we are very hopeful that more precise therapies
will help, especially these young children with severe epilepsy
and mental disorders, cognitive disorders.
Ms. Schrier. Thank you very much. Those are my questions.
Thank you for your research, and I yield back.
Ms. Eshoo. The gentlewoman yields back. The Chair is now
pleased to recognize the gentlewoman from Arizona, Mrs. Lesko,
for 5 minutes of questions, followed by our very patient
waiver-on, Ms. Schakowsky. And then we will go, thankfully, to
the next panel.
So, Congresswoman Lesko, you are recognized.
Mrs. Lesko. Thank you, Madam Chairwoman.
Dr. Koroshetz, has NIH ever used Federal funds to pay for
non-FDA-approved medicines for individuals not in a clinical
trial?
If so, under what conditions, and who or what agency made
these decisions?
Dr. Koroshetz. So NIH pay for non-FDA-approved medicines in
a clinical trial. Only----
Mrs. Lesko. Not in a--so has NIH ever used Federal funds to
pay for non-FDA-approved medicines for individuals not in a
clinical trial?
Dr. Koroshetz. I do not think so, no.
Mrs. Lesko. Thank you. Another question for you, sir, is,
if an expanded access program were available and the medicine
purchased with Federal funds, what kind of program would have
to be created to make it a fair program, in terms of who
benefits?
Dr. Koroshetz. Well, that is a tricky question because I
think we are talking about drugs that have not been proven to
have benefit.
So, as has been mentioned, there is a great need for
patients who are suffering with these deadly disorders to try
something. And so I think that the benefit there would be to
have them feel as though they are getting access to things that
might help, even though the chances are slim.
I think that the issues there are that they could be so
slim that they are either zero or harmful, and I think we also
have to consider the fact that the treatments that we have been
seeing, I would say, are not, you know, powerhouses.
And so what we want is multiple shots on goal. We want
multiple different things to be tried. And so we need patients
who would enroll in these new trials. The ones we have seen so
far just are not that impressive.
Mrs. Lesko. Thank you, Doctor. And my next question is for
Dr. Cavazzoni--sorry if I say your name wrong.
You know, this is--many people seem to be surprised by the
FDA's approval of Aduhelm, considering that the recommendations
from the advisory panel were not really robustly in favor. And
so my question is, can you walk me through why the treatment
was approved?
Dr. Cavazzoni. Thank you for the question.
First, let me say that we greatly value the input from all
our advisory committees, including the input that we receive
from the Neurology Advisory Committee related to aducanumab. So
we looked at the data from this program over many, many months.
And, after exhaustive and detailed review of the data that was
provided in the application over the course of these many
months, we had a discussion within FDA with experts and also
took very careful stock of what we heard from the advisory
committee.
And putting all of that together, we concluded that the
data fully met the criteria for accelerated approval, which is
an expedited approval pathway that Congress gave us in 1992 and
has been used successfully over the past 30 years to bring
therapies faster for a condition, whether it is--an unmet
medical need, such as oncology, infectious diseases, and some
rare diseases.
The accelerated approval pathway has not been used as
extensively when it--in neurodegenerative diseases. In this
case, in the case of aducanumab, the data really made us very
comfortable that all the criteria for accelerated approval had
been met. And we view this as an incremental step, not only for
Alzheimer's and for bringing a potentially beneficial treatment
for Alzheimer's, but also an incremental step in finding ways
to leverage the expedited pathway that we have at FDA to bring
therapies for neurodegenerative diseases faster for patients
who are desperately needing them.
Mrs. Lesko. Thank you, Doctor. My time is almost out, and
so I yield back.
Ms. Eshoo. The gentlewoman yields back. Maybe I should know
a heck of a lot more about this, but I am struck by the irony
on--of the conditions under which the Alzheimer's drug was
approved, understanding that it had limited help to patients,
which is one of the reasons that we are having the hearing
today to try and--you know, to examine what FDA is doing and
bring about the same kind of limited hope, but yet it is hope
and it is help for the ALS community. So I just pose that,
because I--but think that there is an irony here.
The Chair recognizes the gentlewoman from Illinois, Ms.
Schakowsky, whose constituent has been in the hearing room
since we opened the doors at 11:00 this morning and traveled
across the country--except he has been waiting in a wheelchair.
So the gentlewoman is recognized. She is waiving on to the
subcommittee, as she has many times before, always welcome
here.
Ms. Schakowsky. Thank you, Madam Chair.
Dr. Cavazzoni, some time ago one of my oldest, long-term
friends, a dear friend, made a decision to set a date to end
his life. He moved to Canada. He had ALS. And he made a
decision that was representative of having no hope. He chose
death. Well, you, Dr. Cavazzoni, have brought, through the
wonders of science, some hope to people, a person in this room.
Because of this decision that was made, the 2019 FDA guidance,
there is some hope now.
But my understanding is that, when I ask you to produce the
name, the individual who has actually been able to benefit from
this 2019 guidance, that there really isn't anybody that has
been able to access that so far, that there are people all over
this country who--there is this glimmer of hope, but it is
still out of reach.
If I sound upset--because my constituents are here, I have
been getting calls from their friends all over the country who
are begging for a bit of hope. You are going to hear them, and
I hope you will stay to hear them. I know that, you know, once
we move to the next panel, you can leave, but I really beg you
to stay and listen to their testimony.
Could you tell me the people who have actually been able to
benefit? Because my understanding is that it has been quite
impossible to be able to access the two drugs. There are two
drugs that are there now, and maybe my friend, Art, would have
been here to benefit from that. Can you answer me? Are there
people you can tell us--give us a list of names?
Dr. Cavazzoni. Well, first, I really want to say how sorry
I am to hear about the story of your friend, and it is really
tragic, and I really empathize with the suffering that people
with ALS have to go through every day.
I cannot mention--I don't have the names of people with ALS
who may have been----
Ms. Schakowsky. A number, how many?
Dr. Cavazzoni [continuing]. In trials and----
Ms. Schakowsky. How many? Are there people----
Dr. Cavazzoni. Yes, I am sorry, I don't have that
information with me.
I would like to address your point about the guidance. The
guidance is critically important because it provides advice for
developers so that they can put in place clinical trials and
development programs that have the best chance to provide----
Ms. Schakowsky. This is now----
Dr. Cavazzoni [continuing]. In a timely fashion.
Ms. Schakowsky. Excuse me, I--the guidance is about
flexibility. And what I am not understanding is, when you have
people who actually could help advance the science, this is one
contribution they could make, whether or not it extends their
lives. Why we wouldn't do this--because the option is death.
And it is in your power. I mean, what a blessing that is. It is
in your power.
And so I am begging you, I guess, I am, to try to give some
hope that there will be some accessibility due to this
flexibility in the guidance. Is there any more that you can do?
Dr. Cavazzoni. I really hear you, and I can tell you that
we are working every day to find ways to accelerate the
development of therapies and to be as flexible as we can in how
we work with sponsors, how we help them put in place clinical
trials, and also as flexible as we can in how we look at the
data that is derived from those clinical trials, understanding
that, when we are dealing with diseases such as ALS, there has
to be a higher threshold for risk and also greater tolerance
for some residual----
Ms. Schakowsky. Well, I don't know what----
Dr. Cavazzoni [continuing]. Around the----
Ms. Schakowsky. You know, I don't know, and I know my time
is up. I don't know what flexibility is, then, when people are
standing by, willing to contribute to the science and make
discoveries that could help others, and perhaps extend their
lives.
So I yield back.
Ms. Eshoo. The gentlewoman yields back. This concludes our
first panel. And Dr. Hodes, Dr. Koroshetz, and Dr. Cavazzoni,
thank you for your testimony. Thank you for your patience.
Thank you for the work that you are engaged in. You, obviously,
heard a lot of frustration and very direct questions from
Members today. We have an enormous challenge together, as I
said in my opening statement. I believe that we can not only
make progress but, as we are making progress, that we bring
hope to the patient population who are in dire need of hope.
And Members will be submitting written questions to you. We
ask that you answer them in a timely way.
And again, we thank you for being with us.
Now we will hear from a second panel of witnesses today.
Dr. Cartier Esham, the executive vice president of emerging
companies, and senior vice president of science and regulatory
affairs at the Biotechnology Innovation Organization--we all
know it by the short name of BIO.
It is really an honor to have Dr. Merit Cudkowicz. She is
the director of the Sean M. Healy and AMG Center for ALS, as
well as the chief of the Neurology Department at Massachusetts
General Hospital and the Julianne Dorn professor of neurology
at Harvard Medical School.
Dr. Jinsy Andrews is the director of neuromuscular clinical
trials at the Neurological Institute of New York, and the
associate professor of neurology at Columbia University,
Vagelos College of Physicians and Surgeons.
And thank you, Dr. Andrews, for traveling to Washington,
DC, to testify in person.
And last, but certainly not least--what? Oh, I see, yes.
Oh, I am--I have another page.
Mr. Brian Wallach and Sandra Abrevaya are the cofounders of
I AM ALS.
Thank you, Brian and Sandra, for traveling to Washington,
DC, to testify before our committee.
Ms. Yvonne Latty is a journalist and college professor at
NYU, as well as a caregiver to her mother, Ramona Latty, who
has advanced Alzheimer's disease.
And Ms. Kala Booth is a Huntington's disease patient and
caregiver. She is also a constituent of the ranking member of
our subcommittee, Mr. Guthrie.
And now I will recognize Mr. Guthrie to offer a few words
of introduction.
Mr. Guthrie. Thank you. It is great to have Kala here from
Cecilia, Kentucky, Kala Booth. I talked about her earlier in my
opening statement, which seems like such a long time ago, but--
so I have kind of told your story, Kala, if you weren't able to
listen, and look forward to hearing it from your own words, and
appreciate your courage in being here today.
And also we have another Kentuckian, Dr. Esham, who I
think, I found out earlier, went to high school with Thomas
Massie in Vanceburg.
So welcome, as well. Two good Kentuckians here today and
some other wonderful people, so thank you very much. I yield
back.
Ms. Eshoo. The gentleman yields back. I am going to go
first to Dr. Cudkowicz, because she has to leave us.
And I thank you for your willingness to testify, for saying
yes to me when I called you. It is an honor. And I am sorry
that the day has dragged on the way it has. It is something out
of our control, but we wanted to complete our work today, and
thank you for staying with us. You are recognized for your 5
minutes of testimony. And thank you, again.
STATEMENTS OF MERIT CUDKOWICZ, M.D., CHAIR, DEPARTMENT OF
NEUROLOGY, AND DIRECTOR, SEAN M. HEALY AND AMG CENTER FOR ALS,
MASSACHUSETTS GENERAL HOSPITAL; CARTIER ESHAM, Ph.D., CHIEF
SCIENTIFIC OFFICER, BIOTECHNOLOGY INNOVATION ORGANIZATION;
JINSY ANDREWS, M.D., DIRECTOR OF NEUROMUSCULAR CLINICAL TRIALS,
COLUMBIA UNIVERSITY; BRIAN WALLACH AND SANDRA ABREVAYA,
COFOUNDERS, I AM ALS; YVONNE LATTY, CAREGIVER; AND KALA BOOTH,
HUNTINGTON'S DISEASE PATIENT AND CAREGIVER
STATEMENT OF MERIT CUDKOWICZ, M.D.
Dr. Cudkowicz. Thank you, Madam----
Ms. Eshoo. Unmute.
Dr. Cudkowicz. I have unmuted. Can you hear me now?
Ms. Eshoo. Yes.
Dr. Cudkowicz. Thank you, Madam Chair and members of the
House subcommittee, for inviting me to testify today.
Since 1994 I have cared for thousands of families living
with ALS. As a clinical trialist, I designed and led many ALS
trials, including the recent trials of AMX0035 and NurOwn. I am
grateful for longstanding support from both the NIH and the FDA
for my research.
We are at a major therapeutic turning point in ALS. There
have been huge advances in understanding the underlying biology
of ALS, and this has led directly to several exciting drug
targets and positive phase two and three trial results in
people. Yet patients can't get access to these treatments.
We must act now to be both global leaders in the science
and therapy development, but we also must be global leaders in
regulatory approaches by the FDA to help all those living with
ALS today.
There are two pieces of legislation before you, at least
two, that can define success and options for tens of thousands
of people living with ALS and other serious neurodegenerative
disorders. I beg you and ask you to approve them.
The first is the ACT for ALS, which will support expanded
access to ALS investigational therapies for people with ALS who
do not qualify for trials. More than half of the people with
ALS do not qualify for trials. At the Healy Center for ALS at
Mass General we have 130 of our patients receiving 9 different
treatments in expanded access. These patients were not eligible
for any trials. This was their only option.
EAPs can be designed to also learn about ALS. For example,
in one of our EAPs we learned how to best dose the treatment
using biomarkers. In another we found that people's breathing
was getting better. One person noted that they could swim in
the pool again. Another person found that they could be off
their mechanical ventilator for a few more hours a day.
Expanded access absolutely does not interfere with clinical
trials or drug development. It can help it.
The second bill is the Promising Pathway Act that would
allow for conditional approval of promising treatments in phase
two and three. We need this faster pathway for approvals for
treatments in ALS. This is already happening in other serious
illnesses, like cancer, and it is happening for ALS in other
countries, but not in the U.S. This is why we are here today.
Progression in ALS is dauntingly rapid. After diagnosis,
median survival is 2 to 3 years. Again, this is getting more
common. The worldwide number of people with ALS is expected to
rise more than 40 percent in the next decade. There is an
urgency to act.
There was no hope before, but there is hope now. Thousands
of people are studying this illness. There's 160 companies in
it. We understand some of the biology. We have good targets,
and we have positive treatments. This is, again, a major
therapeutic turning point.
We partnered with a small company, Amylyx, to develop the
AMX0035 drug, and we showed last year--a year ago we published
this in New England Journal of Medicine--that this drug slowed
disease progression and it prolonged survival. This is a
combination of two old drugs. We know the safety of these two
drugs. And while this drug, AMX0035, is under review in Canada
for full approval and it is going to be submitted to EMA in
Europe for provisional approval, there is no option for
provisional approval here in the United States. This means a
drug developed and tested here will likely be approved
elsewhere first. That is not good.
We have also heard reports from people in the NurOwn trial
of improvements in function. We don't usually hear this. There
were also some important biomarkers and better responses in
people who were earlier in the disease. We need continued
dialogue with the FDA about how to move those type of
treatments forward.
Our goal is to make sure everyone with ALS has options,
whether that is in the trial or expanded access. And no one
should be told there is nothing to do.
We are seeing pharma companies go to other countries for
their phase one and two studies. They claim that the
regulations are less onerous in Canada or Australia. We are
starting to see drugs approved faster in other countries. My
request is that we continue to be world leaders in regulatory
science and the approaches to accelerate therapy in ALS and
other serious disorders. We need to do that.
We are the leaders in the science. Working together and
creatively and flexibly, we are going to find the cures for ALS
and help our patients and tens of thousands of people. Thank
you.
[The prepared statement of Dr. Cudkowicz follows:]
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Ms. Eshoo. Dr. Cudkowicz, thank you for your most welcome
testimony. I think the sun has gone down--well, it has, it is
about a quarter to 7--but listening to you made me feel like
the sun was rising. So thank you for your marvelous testimony.
And I think that you are going to have a lot of questions from
Members, a lot of feedback. And we sincerely look forward to
working with you.
And thank you for underscoring the legislation that you
support and why and how it will help move the needle. So thank
you.
And I know that you need to leave. We are--you have our
lasting gratitude.
OK, so now who is next?
The Chair now is pleased to recognize Dr. Cartier Esham--I
hope I am pronouncing your name correctly----
Dr. Esham. Yes.
Ms. Eshoo. You have 5 minutes for your testimony, and
welcome.
STATEMENT OF CARTIER ESHAM, Ph.D.
Dr. Esham. Thank you. Can everybody hear me?
Ms. Eshoo. Yes.
Dr. Esham. All right, well, good evening, Chairwoman Eshoo,
Ranking Member Guthrie, and members of the Health Subcommittee.
My name is Cartier Esham, and I am the chief scientific officer
at BIO. And thank you for the opportunity to share our insights
on the state of innovation for medicines to treat
neurodegenerative diseases.
We are the largest trade organization representing
biotechnology companies, and our members range from
entrepreneurial companies developing their first product to
Fortune 500 multinational companies. We regularly publish
reports to help us assess the health of the pharmaceutical
pipeline across different diseases so we can identify and
remove barriers to providing next-generation cures and
treatments to patients and their families. I am going to
highlight three such analyses with a focus on neurology, with
the goal of providing insights to this very important
conversation.
In 2021, we counted 653 clinical development programs from
medicines to treat neurological diseases, 43 percent of which
are for neurodegenerative diseases. By comparison, there are
2,798 oncology clinical development programs. There have only
been a total of 39 FDA approvals for neurological treatments in
the last decade, compared to 123 for oncology. Analysis of
fiscal trends provides us with tremendous insights as to
whether incentives are misaligned or there are other scientific
or development barriers in any given disease area that need to
be resolved.
We focus most of our fiscal analyses on emerging companies,
as they are responsible, alone or in partnership with larger
biopharmaceutical companies, for over 77 percent of the
clinical development pipeline.
Over the past 5 years, we have seen an increase in venture
capital in neurology, setting a record of 1.7 billion in 2020,
a fourfold increase from 2012. While important, it is important
to put these numbers into context; in 2020, venture capital
invested 7 billion in emerging oncology companies.
We have also seen a recent increase in the number of
neurology companies to go public, which is an important way to
generate investment dollars. There was not a single neurology
company that went public in 2012. However, in the past 5 years
we have seen 18 emerging neurology companies go public. But
again, to provide context, in that same time period 75 oncology
companies went public. Thus, while investment in neurological
disease is increasing, it is not at the level we would like to
see or need.
When we look at clinical trial success rates from 2011 to
2020, we found the overall success rate across all diseases is
7.9 percent. Neurology clinical development programs have a 5.9
percent success rate. However, there are important and
informative differences in success rates when you look at
modalities in disease categories. For example, development
programs with patient selection biomarkers have a twofold
higher success rate.
Looking quickly at Alzheimer's, a very complex, very
biologically complex, chronic disease, scientists have
identified more than two dozen genes known to correlate with
increased risk of Alzheimer's. However, despite the
identification of gene mutations associated with Alzheimer's,
many unknowns remain. For example, there are individuals who do
not have Alzheimer's-associated gene mutations that still
develop the disease. Conversely, other individuals may have
fibrillary tangles but do not exhibit dementia.
Our 2019 report on the state of innovation for Alzheimer's
found that venture capital funding of U.S. companies with lead
programs in Alzheimer's was 16 times below oncology funding.
The field saw 87 programs suspended from 2008 to 2019. However,
this year marked the first approval of a disease-modifying drug
for Alzheimer's. And we do continue to innovate. Our report
identified 74 disease-modifying clinical-stage Alzheimer's
programs in the pipeline that are using 10 different strategies
involving 30 distinct molecular targets.
Additionally, our analysis of the preclinical pipeline
found that 23 of the 122 preclinical programs had unique
targets not currently in the clinic. But to deliver on these
innovations and overcome historical odds for neurodegenerative
medicines, creative solutions are required.
As our scientific understanding of disease evolves, so must
the way we develop and review these medicines. Policies
supporting patient-centric, efficient, and effective clinical
development and review will encourage investments into new
treatments.
Additionally, continued funding of basic research to
advance our understanding of the biology of neurodegenerative
diseases, advance our ability to understand and to develop
novel endpoints, and understand how to interpret those
endpoints will arm developers with new targets and approaches
to attack this complex disease.
BIO and its member companies view innovation as key to
helping patients with neurodegenerative diseases. Advances in
science, more choices for patients, and a policy environment
that stimulates investment in R&D are necessary to achieve this
goal. And we look forward to working with Congress to develop
and advance important legislative solutions to achieve this
shared goal. Thank you.
[The prepared statement of Dr. Esham follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Ms. Eshoo. Thank you very much for your testimony, Dr.
Esham.
The Chair is now pleased to welcome and to recognize Dr.
Andrews for your 5 minutes of testimony, and it is just so
embarrassing that you have had to wait all day. We are very
honored to have you here, and we apologize, and we thank you,
and I am happy to finally recognize you.
STATEMENT OF JINSY ANDREWS, M.D.
Dr. Andrews. Thank you, Chairwoman Eshoo and Ranking Member
Guthrie, and members of the committee. Thank you so much for
the opportunity to testify on the challenges and opportunities
of ALS research and development. My name is Dr. Jinsy Andrews,
and I am the director of neuromuscular clinical trials at
Columbia University. I am also a volunteer board of trustees
member for the ALS Association. I also receive NIH funding for
clinical trials, and I serve as a part-time staff physician at
the James J. Peters VA Hospital, caring for veterans with ALS.
My testimony today are my own personal views and not of the VA.
First, I want to thank the committee for persevering
through a very long day, and I would like to also thank the
members of the committee and the House for passing the
consolidated appropriations bill during the break between this
hearing's panel. The ALS community deeply appreciates this, and
increasing funds to the NIH, including ARPA-H and other Federal
research programs, are critical for ALS and other
neurodegenerative diseases.
I also urge you to increase funding for the DoD ALS
Research Program.
I am here today to ask for your help because the ALS
research and development is not moving fast enough, as we heard
today. The ALS community needs your help to ensure that the FDA
accelerates drug development, approval, and access to effective
new ALS treatments. When we all work together, we have seen the
ability for regulatory flexibility and speed. Congress should
urge the FDA to use their existing regulatory authority to move
much more quickly on ALS drugs.
Specifically, the ALS Association has urged Congress to
pass the ACT for ALS Act to provide increased access to
experimental treatments for people with ALS, while funding new
research. The ALS Association has also urged Congress to
increase Federal funding for research, ALS research, and to
develop a conditional approval pathway modeled on the
successful experience of the European Union.
I have cared for people with ALS and conducted clinical
trials for over 15 years in both an academic and industry
setting. In 2013 I attended a public hearing for ALS held by
the FDA, where many people with ALS at that time shared that
they are willing to take higher risks, that time is a luxury
that they just don't have, and that they had limited access to
experimental treatments. Many of those patients, including the
ones that I cared for, have since died. Time is of the essence.
People with ALS urgently need effective new treatments.
The FDA should be fully funded, fully staffed, and provided
the regulatory authority they need to be fast, effective, and
transparent for ALS clinical trials and drug approvals. Making
approval decisions about promising therapy is never easy,
especially in fatal diseases. But year after year, people with
ALS have shared with the FDA, with Congress, and basically
anyone else who will listen that they are willing to accept
greater risks, that anything that retains function, that
provides more time, is meaningful to them and that access to
new treatments, including ones prior to FDA approval, is a top
priority, because right now there is no cure for ALS.
There are also opportunities for manufacturers to make ALS
clinical trials more efficient, more impactful, and more
respectful for people with ALS. That includes expanded access
to experimental therapies, which is not often provided by the
pharmaceutical companies that are in the ALS space, typically
because they are small, or they don't have resources. And in
contrast, big pharma companies that may be able to provide
expanded access don't invest in ALS programs until they are
derisked. All clinical trials should be accessible to people
with ALS by including open-label extensions and expanded
access, which, if it is designed appropriately, could collect
data regarding safety and tolerability.
Additionally, I am going to emphasize what Dr. Cudkowicz
emphasized: providing expanded access to patients outside of a
clinical trial can be accomplished without impeding the
completion of a clinical trial in ALS. We have done this and we
are doing this by offering expanded access to patients who are
not clinical trial eligible. We stagger the enrollment of
clinical trials in offering expanded access, and clinical trial
participants should be assured that they have access to the
experimental therapy after they have completed their
participation in the formal clinical trial.
This--there is a perception out there that ALS is rare, but
we have all shared stories today about how we have been touched
by neurodegenerative diseases, so I don't have to explain much
more than that. It is important for us to act now. Thousands of
people with ALS are dying today and don't have options. Anyone,
any one of us, are at risk of developing ALS or a
neurodegenerative disease. Our veterans who served this country
are twice as likely to develop ALS than the general population.
When someone is told they have ALS, they have a zero
percent chance of survival. Pancreatic cancer even has a 5
percent chance of survival. Let the people that get diagnosed
with ALS not have to face what people with ALS are facing
today: a lack of access to treatments. You have the power to
change that.
And especially I want to thank the committee for the
opportunity to testify and, of course, thank the panel before
us, that we are able to participate in this important hearing
today. Thank you.
[The prepared statement of Dr. Andrews follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Ms. Eshoo. Dr. Andrews, thank you. I think all of us more
than welcome your testimony. And the clarity and the passion
that you delivered it is really welcome here.
Did you have any--just very quickly--recommendations on the
legislation that is at hand, and what you would say about it?
Dr. Andrews. I have to agree, and I am going to say that
almost all of the ALS community agrees.
As Dr. Cudkowicz mentioned, these pills that are on the
floor can make transformational change, help preserve clinical
trial integrity, and help access to experimental therapies. And
actually, in those cases of access, in expanded access, we can
actually gain data to help understand the disease and improve
our understanding of the biology for the future, for more
effective treatments down the line.
Ms. Eshoo. Thank you very much. And we ask that--I am sure
there are many Members that are going to submit written
questions to you, and we will look forward to hearing back on
those, the questions being answered by you on a timely basis.
So thank you very, very, very much.
The Chair is now so pleased to recognize our two guests
that have been with us since the doors were unlocked this
morning.
You knew that it was going to be a long day. You had no
idea that it was going to be all day and part of the night. We
are blessed to have you. We thank you for traveling across the
country. I said to you when I greeted you this morning that I
thought you were both profiles in courage, and that you are.
So, Mr. Wallach, welcome again, and thank you.
And Ms. Abrevaya, it is more than an honor to have you, and
we look forward to your testimony now.
I should--I wanted to add, because I don't want him to
leave--he left before, and I didn't recognize our colleague,
Mr. Quigley from Illinois. He is one of the--he is the
Democratic lead on the legislation that Congressman Jeff
Fortenberry from Nebraska--they have worked so hard on that
bill. I look forward to this committee considering it.
We want to thank you for the work that you have done, and
thank you for being here for the second time today. But I
didn't get to introduce you and acknowledge you. You scooted
out before I could say something before.
At any rate, it is your 5 minutes. And if you go over time,
the Chair is not going to lower any gavel.
STATEMENT OF BRIAN WALLACH AND SANDRA ABREVAYA
Ms. Abrevaya. Thank you so much. Well, we would be here all
night and into the morning, because this is a critically
important hearing, and tens of thousands of ALS patients have
been waiting just for this moment. And we are so grateful to be
here.
So Chairwoman Eshoo, Chairman Pallone, and Ranking Members
McMorris Rodgers and Guthrie, thank you for the opportunity to
testify before you today.
Mr. Wallach. My name is Brian Wallach. I am 40 years old. I
have been fighting ALS for 4 years.
Ms. Abrevaya. I am Sandra Abrevaya. I am a caregiver. I am
Brian's wife, and as you will hear today, I will be his voice.
We have two young daughters. One turned 6 two weeks ago, and
our second daughter, she turns 4 on Saturday.
Professionally, I have served as a staff member in the
House, in the Senate, in a Federal agency, and Brian and I
together served as staff members in the White House. At the
time that Brian was diagnosed, he was 37 years old and he was
an assistant United States attorney.
Mr. Wallach. This is our closing argument for our lives.
Ms. Abrevaya. This is our closing argument for our lives.
As you just heard from the panel's expert ALS clinicians,
we are all aligned. ALS, while currently a 100 percent fatal
disease, is no longer hopeless. Today there are more promising
therapies that are slowing or stopping ALS in people--not in
animal models, in people.
So the question we all need to answer today is the one I am
so tremendously grateful that so many Members, perhaps a record
number of Members, asked in a unified voice today: How do we
get the tens of thousands of ALS patients, alive and dying
today, using the tools and the science that currently exist,
therapies that can keep patients alive to be here, to see
cures?
And I am excited to tell you that the answer is abundantly
simple: Make the FDA act with urgency and regulatory
flexibility. It promised in its 2019 guidance to approve the
drugs that are stalled right now. It is abundantly simple, and
it is within your power.
Despite what you heard from the FDA this morning, it has
never historically required a biomarker to approve an ALS
therapy. Instead, FDA has used two outcome measurements to
approve therapies in the past: survival length and the ALSFRS
scale, which measures a patient's ability to do things like
walk up the stairs or cut their own food.
I think it is extremely important for this committee to
know the data, the facts. I can tell you, Brian and I have done
our homework. Radicava is a drug that was approved for patients
in 2017, and the FDA cited that it slowed patients' progression
on the ALSFRS scale. The trial for AMX0035, one of the two
drugs being stalled now, also showed that it did the same
thing, it slowed progression on the ALSFRS scale. And, I might
add, it gave patients an average of 6\1/2\ months longer to
live, when compared to the placebo.
Interestingly, AMX, turns out it is headed for speedy
approval in Canada and Europe. And it is based on the very same
data that the FDA had a year ago. It certainly begs the
question of why didn't FDA approve this a year ago?
The trial for the second therapy being stalled is called
NurOwn, and that trial showed that, for those patients who
started the trial with a score of 35 or higher on the same
ALSFRS scale and received the drug, their score at the end of
the trial was 2 points higher.
We heard again and again today, ``We need science, we need
data.'' I am telling you what the data was. It is publicly
available. For patients who entered the trial with a 35 or
higher, they scored 2 points better than the placebo. You can
go back and look at Radicava on the FDA website. That is the
exact same type of success rate that Radicava had when it was
approved in 2017, which begs the question, why has this
therapy, NurOwn, which is successful for a subset of the
patients in the trial, not been approved?
Moreover, after that NurOwn trial, several patients have
been able to access it through a small, expanded access
program, and a number of them have seen it halt their
progression, or improve their function.
Mr. Wallach. Phil Green.
Ms. Abrevaya. Phil Green is a friend of ours who can now
buckle his seatbelts and take his own pills. I can tell you
Brian can't do either of those things, and we just turned 40.
For a clearer explanation of expanded access than I think
we were all provided with today, I would encourage you to go to
FDA.gov. On that site you will see very clearly that, just as
Dr. Andrews articulated, in order to be eligible for expanded
access, on their website, ``patient enrollment in a clinical
trial is not possible.''
Let me be super clear: Expanded access in no way endangers
a clinical trial.
Second, it was great to hear the FDA this morning say they
are so supportive of expanded access for patients. If that is
true, I would ask the FDA to publicly announce their support
for ACT for ALS, which will fund expanded access programs. As
Dr. Andrews also said, again, you will see the ALS clinical
community and the ALS patient community is all aligned,
uniform. Expanded access is not affordable for the small
biopharma companies that are currently in the ALS scene. We
need the funding in ACT for ALS. So if anybody in this room
wants to see patients get access to expanded access, you have
to do that by giving it funding. And ACT for ALS is the vehicle
to do so.
The FDA's recent decisions are all the more shocking in
light of their own September 2019 guidance, which, again, I am
so grateful that so many Members brought up today. However, it
said it would exercise flexibility and urgency, and sadly, what
we have seen is even less urgency and less flexibility. They
have asked the two drugs I have repeatedly mentioned, AMX0035
and NurOwn, to run another large placebo-controlled trial prior
to any approval. That means these therapies won't be approved
for 4 years.
Let me remind you, when you are diagnosed with ALS, you are
told you have 2 to 5 years to live. So if this won't be on the
market for 4 years, every single ALS patient, including us,
will be dead before having access to either therapy.
Congressman Upton asked an excellent question of the FDA
today: How can Congress help?
Mr. Wallach. FDA did not answer his question.
Ms. Abrevaya. FDA did not answer that question. So we, as
the patients who are dying, whose lives are on the line, we
will answer it for you.
One: Urge FDA to approve AMX0035 today.
Two: Urge FDA to approve NurOwn for the over-35 subgroup
today.
Three: Pass ACT for ALS, which funds expanded access,
today.
Four: Pass the Promising Pathways Act to provide a
conditional approval pathway for rapidly progressing fatal
diseases, even beyond ALS.
I beg of you. There are tens of thousands of patients who
are watching this from their homes, wheelchair bound, some of
them on life support, watching this today. Their hope is in
this hearing. Some of them have waited and postponed their
decision for suicide to see this hearing.
I don't think you understand what this hearing means to us.
Please do not let another generation of ALS patients die in
pursuit of the perfect. Please let this be the first generation
to survive.
Mr. Wallach. We want to live. You have the power to make
that possible.
Ms. Abrevaya. We want to live. You have the power to make
that possible. Thank you.
[The prepared statement of Mr. Wallach and Ms. Abrevaya
follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Ms. Eshoo. I think that there is a sound building across
the country of applause from the entire ALS community,
listening to you offer your testimony and your message to this
committee. We are so in debt to you. We thank you for your
clarity. We thank you for your courage, and thank you for the
patience that you had to exhibit today. And I don't think there
is a--let me put it this way, in a positive way, that every
single member of this subcommittee is moved by what you said
and that we are determined to pursue exactly what you set out
in your testimony. So thank you, thank you, thank you, thank
you.
All right. Next we have Ms. Yvonne Latty, and we welcome
you, and we thank you for being willing to testify. We
apologize to you, as well, for having to spend a day and part
of the night waiting to testify, but I am really pleased to
recognize you now for your 5 minutes of testimony.
STATEMENT OF YVONNE LATTY
Ms. Latty. OK. Chairwoman Eshoo, Ranking Member Guthrie,
and distinguished members of the committee, thank you for the
opportunity to tell my family story during today's hearing.
I am a journalist and a college professor at New York
University, but I sit here before you as a daughter. My mom,
Ramona Latty, a Dominican immigrant, has advanced Alzheimer's
disease and lives in a nursing facility in the Bronx. She is
88, and I am her only living child.
This disease is rampant in my community. In general,
Latinos are 1.5 times more likely than non-Latino Whites to
develop Alzheimer's disease. My chances of getting the disease
are also slightly elevated because my mother has it. The health
issues that plague our community--high blood pressure, heart
disease, diabetes, and stroke--make us more vulnerable. The
statistics for the African-American community are even worse.
They are 2 times more likely to get the disease than White
people.
But this disease is not who my mother is, even though it
has taken control of her life. My mom was born in Santo
Domingo, a city on the coast of the Dominican Republic. She
grew up poor in the--she grew up poor. In the eighth grade she
had to drop out of school to take care of her brother so that
her mother could work. My mom was a big dreamer who wanted
more, so she wanted out of Santo Domingo, where she worried she
would live a life with no work, no money, and no hope.
In 1950 my mom immigrated to New York. Coming to America
was her dream come true. She worked in factories and went to
beauty school. She met my dad, Albert, a child of Jamaican
parents, at a beauty parlor in Spanish Harlem where she worked.
They were married 9 months later and had two daughters, me and
my big sister, Margie. My dad and my sister have both died. And
so it has been the two of us for a long time.
About 6 years ago my mother started to show signs of
dementia. She was losing things and was confused. Then she
began to hallucinate a boy who lived on top of her
refrigerator. I discovered she gave all her money away to mail-
order psychics who promised her riches. We spoke every day,
sometimes multiple times a day. I found myself thinking about
her all the time, worried. So we turned to her doctor, who
suspected dementia and referred us to a neurologist.
I remember the day we went to his office in the Bronx,
where Black and Brown people packed the waiting room. After a
series of tests, he told us dryly that she had Alzheimer's
disease. He gave me some URLs, told me to Google it, and sent
us on our way in less than 10 minutes. It was clear he had no
time for us. He barely looked at my mom. I went home and cried.
This is not uncommon in the Latino community. Despite a
higher risk for Alzheimer's, Latinos and Black Americans face
steep inequities in accessing a formal diagnosis. According to
a recent study of Medicare beneficiaries, Black Americans and
Latinos were less likely to receive a timely diagnosis when
compared to non-Hispanic whites.
But I was ready to fight this disease. I switched
neurologists, and the new one referred her for a clinical trial
to help with the hallucinations. While Latinos make up roughly
17 percent of the U.S. population, they make up less than 2
percent of the participants currently enrolled in Alzheimer's
research funded by the National Institutes of Health.
Clinical trial enrollment represented hope against a
disease that is often seen as a death sentence. I was thrilled
that she was going to be part of one and hopeful that it could
help her, but it was grueling. She lived in the Bronx, and I
live in Philadelphia. I had to get her to New York Presbyterian
Hospital in Washington Heights every week for 6 weeks. She had
to visit a series of doctors and have psychological exams
before the medicine was administrated. We barely had enough
compensation to cover an Uber from the Bronx to reach the
research site.
Research accessibility in communities like the Bronx is a
systematic issue. According to an analysis by the University of
Wisconsin, the geographic distribution of the Nation's 31
federally funded Alzheimer's Disease Research Center's marquee
research sites skews toward the most wealthy neighborhoods.
Balancing her research participation and my full-time job
was another challenge. I was teaching and had to ask my
coworkers to cover me so I could be at every appointment. I was
able to make it work because my employer offered paid family
and medical leave and flex time. The millions of Americans are
not so lucky.
Paid leave is an urgent health equity issue for dementia
caregivers. According to a national survey of unemployed
dementia caregivers, less than half have access to paid family
and medical leave policies like me. More than half of
caregivers who utilize paid family and medical leave benefits
reported it resulted in better emotional well-being compared to
the 23 percent of caregivers who didn't have access to these
benefits.
Having this flexibility was critical as my mother's care
became more complicated. She had to take the medicine at a
certain time, but she couldn't take it on her own. Plus, she
only had a part-time aide, and so I had to scramble for help.
It was exhausting. And in the end, she got the placebo version
of the trial drug. After all that, the treatment hadn't done
anything, and there was not much else they could do but wish us
luck and send us on our way.
Despite the initial engagement and our interest, we were
never contacted again about opportunities to participate in a
clinical trial. Things continue to get worse. Soon the boy
above the fridge was joined by a new hallucination: ICE. I
would get frantic, late-night calls that a black ICE van was
circling the block around her apartment, and she would beg me
to help her. They were coming to deport her, she said. I tried
to tell her they couldn't take her away, she was a naturalized
citizen.
Finally, her aide found her wandering in the street one
morning. She was no longer safe. She needed 24-hour care, and I
had to place her in a nursing home. It was the hardest thing I
ever had to do in my life.
So now, after living through a pandemic, in which every
floor of her nursing home was infected with COVID-19 and I had
no physical contact with her, after a year in which my mother
further declined, she is now nonverbal and can no longer feed
herself. And every day I wait for the call that says she is
passing.
I am asking your committee to think of her, me, and so many
others like us who journey through this disease. So here is
what I am respectfully asking on her behalf: Improve equity and
diagnosis and detection of Alzheimer's to expand treatment and
care options for families; improve equity in Alzheimer's
clinical trials to deepen our understanding of the disease in
high-risk communities; establish a paid family and medical
leave policy to help families navigate work and medical care;
support a national Alzheimer's prevention goal to give hope to
families.
Without the committee's action and society's commitment to
brain health equity, Alzheimer's will be the last chapter in
the lives of more and more Americans. It is time to change the
way this story ends. Thank you.
[The prepared statement of Ms. Latty follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Ms. Eshoo. Thank you, Ms. Latty. I hope you realize how
powerful your testimony has been, and that, even though we kept
you waiting all day, that none of that time that passed really
diminished the power of your testimony, and the story of your
mother and you, as her daughter, is the story of so many
Americans in our country. And I look forward to the day where
the policies that you articulated that are needed are actually
put into place by the Congress, because it would just serve the
American people so well, as they struggle. These are 24-hour
struggles on a daily basis in people's lives.
I had the, I think, the privilege to take care of my
parents, and it was a huge responsibility, and I was working
and everyone else in my family was working, as well.
But there were so many things that you brought up that
others have, that I didn't have to carry the burden of. These
are huge burdens.
And this is by no means--I think some people think of these
services as handouts. I say go walk in your shoes for 24 hours.
So thank you for walking in your shoes into our lives today at
the committee.
And now I would like to recognize Ms. Kala Booth. As I said
earlier, she is a Huntington's disease patient and a caregiver.
We are prepared to hear your 5 minutes of testimony.
Thank you for your extraordinary patience.
STATEMENT OF KALA BOOTH
Ms. Booth. Thank you. Good evening, and thank you for the
opportunity to share my family's story, and the story of so
many HD families. My name is Kala Booth. I am 34. I am the
fourth known generation in my family to have Huntington's
disease but only the second to be officially diagnosed. I am a
patient, I am a caregiver, and more importantly, I am a voice.
Today I am a voice for the HD families who do not have one.
Over the years I have taught myself to emotionally
disconnect. This allowed me to be able to separate the
Huntington's disease from the person. Twice I have watched a
broken system turn a devastating situation into an almost
unbearable one.
Huntington's disease is a rare, inherited disease that
causes degeneration of the brain. It affects each patient
differently. The symptoms are different. The progression time
is different. But what is not different is it is fatal and
there is no cure. Unlike other neurological diseases, symptoms
of HD typically develop in the prime of a person's life, their
40s. These years are typically a person's highest-earning
income years, the middle of raising families, or planning for
retirement. However, HD disrupts all of that and physically,
emotionally, and financially drains families.
In the late '90s, early 2000s, when I should have been
creating memories with my papaw, I was emotionally
disconnecting from him. HD had turned this previously gentle
man into someone who beat my mamaw black and blue, someone we
always needed to keep a phone nearby in case we needed to call
911.
Before HD, my papaw was a man who stepped in as a father
figure for my dad, a man who drove across country to wherever
we were stationed. A broken system would send my papaw to
Central State Mental Hospital, a broken system that didn't have
the ability or facilities to care for someone with HD, because
he could be a danger to himself and the staff. A broken system
ended with my papaw passing away and my mom spending 5 years in
court, battling to settle those bills.
Fast forward to 2015, the third generation, a second path,
and another interaction with a broken system. My mom, Marsha,
is what you would describe as a ray of sunshine, the type of
person to never say a harsh word. My mom decided, when my papaw
was diagnosed with HD, that she didn't want to be tested. She
wanted to live her life to the fullest. And when it was God's
time, He had a plan. My mom had hope, hoped she didn't have the
disease, hoped there would be a cure. But honestly, she didn't
want to be a burden, and she sure didn't want to have to take
an MRI.
But man, if we had only known how valuable those results
would have been. November 2015, my mom's HD started manifesting
as paranoia. The less she slept, the worse it got. Eventually
she ended up in a psychiatric ward, receiving treatment for
what doctors thought was schizophrenia. Thirty days it took to
get her home. Thirty days we drove to Louisville to see her for
one hour. Thirty days I watched my dad's heart break each time
we had to leave her.
They didn't understand she was experiencing the progression
of HD. Over the next few years, her health slowly declined. She
went from being a top real estate agent in the county to
needing help calculating figures. She was no longer able to
drive. She is losing control of her swallowing, and she has
mentally declined to childlike behaviors. So my dad and I
always make sure to be nearby.
November 2019, we applied for her Social Security
disability income. It was declined. We appealed. It was
declined. We hired a lawyer, and in March of 2021 a broken
system finally awarded her SSDI and Medicare coverage.
A fourth generation, and new approach. In 2018 I chose a
more hands-on approach. I wanted to have all the facts and all
the options. There was a fear of medical insurance finding out.
There was a fear of life insurance finding out. So after I got
all my affairs in line, I was able to do genetic testing off
the record. The results came back. I had HD.
I was tired and living in fear. And after the battles my
family had faced, I decided it was time to help make a change.
I now have an amazing team of doctors and nurses on the record.
I participate in clinical trials, and I help with advisory
boards. And I am here to help fix a broken system.
I urge Congress to take the following steps to help
patients and families living with Huntington's disease.
Pass the Huntington's Disease Parity Act this year. The HD
Parity Act eliminates the Social Security Disability Insurance
and Medicare wait periods. As you can see from my family's
story, HD families often spend years securing a disability
determination, then are forced to wait another 6 months to
receive SSDI cash payments. And 2 years for medical care
coverage is unacceptable. This policy must be changed.
Expand the focus of the NNCSS to include Huntington's
disease, and require the FDA and NIH to work with companies
that are researching HD cures to design trials that recognize
the uniqueness of HD--that the disease onset and progression is
different from any other diseases. The HD community needs more
research and cures as possible.
Thank you.
[The prepared statement of Ms. Booth follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Ms. Eshoo. Thank you, Ms. Booth, for your important
testimony. And again, on behalf of all of the members of the
subcommittee, we apologize for keeping you waiting all day and
into the evening. But you enriched our hearing with your
testimony, and we very much appreciate it.
We now have--we have completed the testimony of our
witnesses on the second panel and will move to Member
questions, and I will recognize myself for 5 minutes to ask
questions.
To Dr. Andrews, as a researcher on the front lines of ALS,
what do you need from Congress and the FDA to continue to
innovate on clinical trial design?
Dr. Andrews. I think it is very important to urge FDA to
use its existing regulatory authority and abide by the 2019 FDA
guidance when reviewing clinical trial results in the context
of the disease that they are reviewing for.
It is important to note that something like ALS, that has a
zero percent chance of survival, if something shows a clinical
benefit in retaining function and slowing disease progression
and extending survival, yet is safe and well tolerated, the
traditional framework that we typically--that is typically used
by the FDA doesn't work for a fatal, degenerative disease like
ALS. In doing so, this can spur innovation and interest of
other pharmaceutical companies to come in the space.
When we get stuck in these types of situations, it actually
drives people away from that disease, and we lose that
interest. So I think, in that way, the two bills we talked
about and urging some regulatory flexibility and abiding by the
FDA guidance that was finalized in 2019 can help that process
along for clinical trials.
Ms. Eshoo. There is something that kept coming up that the
witness from the--Dr. Cavazzoni kept mentioning, and that was
biomarkers. And it seems to me that the FDA kind of stood on
that, ``Well, we have to have biomarkers, we have had
biomarkers'' and other, you know, drug development and all of
that. It seems to me that the needle is stuck there.
And can you cast some light on this, because I pointed out
in a comment, after what was stated, that it was--there seemed
to be a real irony when there are results, even though they are
limited, but they are desperately needed, and we don't move in
that direction, but again, back to the biomarkers. Can you
enlighten us on this?
Dr. Andrews. Yes----
Ms. Eshoo. Please.
Dr. Andrews [continuing]. Thank you for that question. It
is a very good one. And it is important to understand. It is
true that, in ALS, we don't fully understand the biology. And
if we did, we could cure it today.
Ms. Eshoo. Exactly.
Dr. Andrews. However, when we are talking about biomarkers,
that is not what a patient feels or functions. We have to
understand that biomarkers will develop if we continue to do
clinical trials and collect serum, spinal fluid, urinary
samples and understand the biology. So that is why continuing
Federal funding for ALS research is critical in parallel to
helping gain access to experimental therapies for those living
with the disease.
We can do both. You know, it is such----
Ms. Eshoo. This sounds like the European model to me.
Dr. Andrews. So----
Ms. Eshoo. In a way.
Dr. Andrews. This is----
Ms. Eshoo. Is it?
Dr. Andrews [continuing]. Part of the reason why the ACT
for ALS Act can help in this situation. It is difficult for us,
as Americans, to see potential therapies get faster review and
approvals because regulatory review processes abide by
different legislations. This could help harmonize us globally
and keep us leaders of developing, innovative therapies for
these types of conditions.
Ms. Eshoo. Thank you very much.
To Dr. Esham, how can we get more companies to participate
in expanded access?
Dr. Esham. Thank you, Chairwoman, for the question. In
terms of expanded access, generally speaking, you know, each
clinical development program and each company do have unique
and multiple factors they have to evaluate, including the
ethical and resource capacities to stand up programs that
include establishing rationale and criteria about how to make
decisions about which should be granted and on which basis they
would be denied.
There are other factors, such as the questions around the
ability--the capacity to scale up supply, as well as thinking
through any impact on clinical trial enrollment. So it--there
is not a one-size-fits-all relating to each clinical
development program or each company as to how they approach
expanded access. And the goal, the primary goal remains to get
medicines approved so that they are available to all patients.
I will note just quickly--I don't want to cut time, but the
requirement for companies to provide information on expanded
access that was passed in Cures, there may be something to
think through there, to make sure that more people are aware
about how to find expanded-access programs. So that is
something maybe we can think through and work with you all on.
Ms. Eshoo. Thank you very much. My time has--I have
exceeded my time.
The Chair now is pleased to recognize our wonderful ranking
member of the subcommittee, Mr. Guthrie, for your 5 minutes.
Mr. Guthrie. Thank you, Madam Chair. Thanks to everybody
for being here.
And Kala, I know that, when we talked earlier this week, I
was talking about how important it is that patients and
advocates come before Congress. It is vitally important. I
think people get the impression that we are up here, more
walled off. And, as from the testimony of the Wallachs and
Abrevayas, it moves us, and it really does--hopefully, will
inspire most of us to act.
In the most important meeting I have had in 12 years here,
I can tell you the--and we have, what, 8 or 10 a day? And the
one that I could point to as my most moving was a 9- or 10-
year-old. Her name was Shelby Enzer. I will say her name, her
mom was Kay Enzer, the dad was Mitch, and her brother was
Tanner. And she came here as a 9- or 10-year-old with ALS, and
she said, ``My father cannot hug me anymore, but I am here
because I want to make sure no other little girl goes through
what I am going through.'' And God rest his soul, a wonderful,
wonderful man, and just a great family. And it--I have always
been an advocate for it, because they showed up.
I didn't have personal experience with ALS. Unfortunately,
a lot of us have personal experience with at least one of the
ones we are talking about today. And Alzheimer's is one that I
have in my family.
So it is all important, and thanks for being here and
sharing your stories and making a tremendous effort to be--
whether you are on Zoom, or whether you came here today, the
tremendous effort to be here. It is important. I am glad you
are here.
So, Kala, when we talked earlier this week you mentioned
your past involvement with a hopeful clinical trial for HD and
shared some exciting news of that this week. Your mother had
her first appointment for a clinical trial. Can you describe
the significance for you, personally, of having the opportunity
to participate in a clinical trial, and now your mother?
And can you share with us some of the changes you would
like to see happen to better reflect the needs of the HD
patient community?
[Pause.]
Mr. Guthrie. Kala, you may be on mute, if you are----
Ms. Eshoo. Yes, you have to unmute.
Ms. Booth. Can you hear me?
Mr. Guthrie. We hear you now----
Ms. Eshoo. Yes.
Mr. Guthrie [continuing]. Yes.
Ms. Booth. Being part of the clinical trial gave me
purpose. It helped me find my path. I think God wants me to
help others in joining the--put that into action. Knowing that
I have HD brings a lot of challenges, and I had to make a lot
of tough decisions before most people my age. However,
enrolling in a clinical trial helped me see that I can help a
lot of people with HD and those at risk. Families are hoping
for treatments to delay the disease, or even cure HD.
Clinical trials give me hope. The clinical trial I was in
had so much positive talk to be a breakthrough treatment to
help me, my family, and so many other families. The trial
didn't work out, but now my mother is enrolled in her first
clinical trial.
Once HD does damage to your brain, it can't be fixed. So
the sooner you get treatment or a cure is better.
As far as what can be done, being part of the trial and
working with my local Center of Excellence, I have learned that
the FDA has been a good partner with the HD community and its
researchers. However, I would like the FDA to think about ways
it can work with the communities to recognize the difference
that exists from patient to patient, so that we aren't missing
out on treatments that could help HD patients.
Mr. Guthrie. Thank you. My friend, Adam Kinzinger, a member
of this committee, is working on--with Social Security that you
talked about. And it sounds like your family had a difficult
time getting your mom's disability application approved, and
that it felt like the system was uninformed or didn't
understand HD. How did that impact the experience with your
family?
Ms. Booth. So the disability process was very difficult and
frustrating. It took 16 months to finally get my mom's
application approved. She was denied two times, and it wasn't
until we hired a lawyer that she was finally approved.
Luckily, because we involved a lawyer, the judge backdated
her eligibility to receive her SSDI and Medicare right away.
However, I know from other HD families who cannot afford a
lawyer it takes much longer to get approved, and then the
waiting periods still apply. Many individuals and families,
including mine, try to support the HD patient so that they can
work as long as they can and try to prolong progression,
maintain income, and health insurance through their employer.
So by the time that they have applied for a disability, they
really need it. Making them wait years to get through the
process, and even longer wait times, is unacceptable.
HD is devastating physically, emotionally, and financially.
Not receiving the SSDI payments or access to the Medicare
immediately is an added hardship that HD families should not
have to endure. That is why I am asking Congress to pass the HD
Parity Act. HD families need your help.
Most people have not heard of Huntington's, and even those
who have don't really understand it. That was our experience
with going through the SSDI process. While we learned that HD
is on the Social Security Administration's compassionate care
list, it did not seem that anyone understood HD or applied
compassion to my mom's case. For HD patients, their limitations
may not be obvious to someone who is physically disabled. The
first symptom that many HD patients experience are cognitive
and behavioral. Uninformed staff and judges deny the
application because they don't understand the way HD impacts a
person.
For people like my mom, who do not want to get tested to
confirm they have HD, actually makes the disability process
even more challenging. Disability staff and judges need to be
better educated about how HD--to ensure patients get their
disability termination quickly.
I would recommend requiring the SSA to consult with HD
Center of Excellence. The providers and staff at the Center of
Excellence are true experts. However, even if it only takes 6
months for an HD patient to get through the SSDI process, the
existing wait time still delays the Medicare coverage for 2
years and cash payments for 5 more.
Mr. Guthrie. Thanks, Kala. I think I have run out of time
to ask questions, but--and thanks for answering that. I know
that Representative Kinzinger appreciates your answer, and I
will yield back.
Ms. Eshoo. The gentleman yields back. The Chair is pleased
to recognize the chairman of the full committee, Mr. Pallone,
for your 5 minutes of questions.
Mr. Pallone. Thank you, Chairwoman Eshoo, and let me really
thank everybody for testifying today. As the chairwoman said,
this was really incredibly informative.
I mean, we have heard from some of you, you know, in the
last few months, but the testimony today really makes a
difference in our understanding, I think, of where we need to
go.
So I just wanted to mention, obviously, there was a lot
of--from patients that find--there has been a lot of
information from patients that finding access to a clinical
trial can be extremely difficult, based on age cutoffs, cutoffs
based on disease progression, and other factors. And the FDA
has even spoken about the tension in designing trials so more
people can participate, while understanding the clinical
benefit.
In the FDA's guidance for developers of ALS treatments, the
agency advised that more patients could participate in clinical
trials if developers broadened the criteria, allowing for one
group to be considered for a primary analysis and a broader
group to be used for a secondary and supportive analysis.
So I wanted to ask three of you, starting with Dr. Esham,
to your knowledge, Dr. Esham, how has industry responded to the
guidance? Is greater guidance from the agency needed in this
space?
Dr. Esham. Thank you, Chairman Pallone. I don't know that I
can answer that question with specificity, but I will say, in
general, when you think about guidance, I know that the 2019
was welcome, as it was--had been some time since that--any
guidance had been updated.
And in an area like this, in such a serious and life-
threatening disease, it is important to keep an iterative
process that includes engagement between the regulators, the
patients, the medical community, and the biopharmaceutical
industry to make sure that the guidance is keeping pace with
the needs and understanding of science, generally speaking.
I also just quickly want to point out--I don't want to take
up all of your time, but as to the question of inclusion and
exclusion criteria, I think there is, in addition to what you
are raising in this space, there is a larger conversation
really looking about how we think through inclusion and
exclusion criteria, based on what we have learned during the
pandemic. And I know a lot of our member companies are really
reexamining how we should be thinking through that to ensure
that there is not bias.
And then, in terms of trial design, if we brought in that,
how can we make sure--how can we use all the modern
computational tools at our disposal in today's time and in
tomorrow's, only to increase--to really improve how we are able
to analyze data across subpopulations or, particularly in
diseases with heterogeneity and outcomes.
So there is a lot of interesting work going on, and we are
certainly ready to advance all of those concepts.
Mr. Pallone. Well, thank you. I want to get to Mr. Wallach
and Dr. Andrews, as well. Let me ask Mr. Wallach. I know your
organization has done a lot of work to track available clinical
trials and their exclusion criteria. How would you assess how
developers are doing in implementing that portion of the
guidance, and how could they do better?
Mr. Wallach. I think it is fair to say----
Ms. Abrevaya. I think it is fair to say----
Mr. Wallach [continuing]. That developers have taken that
guidance to heart.
Ms. Abrevaya [continuing]. That developers have taken that
guidance to heart.
Mr. Wallach. But it takes two to tango.
Ms. Abrevaya. But it takes two to tango.
Mr. Wallach. And FDA has not taken the guidance to heart.
Ms. Abrevaya. And FDA has not taken the guidance to heart.
Mr. Wallach. So what I mean by that----
Ms. Abrevaya. So what I mean by that----
Mr. Wallach. For the NurOwn trial----
Ms. Abrevaya. For the NurOwn trial----
Mr. Wallach. They had more patients----
Ms. Abrevaya. They had more patients.
Mr. Wallach [continuing]. Further----
Ms. Abrevaya. Oh, the NurOwn trial had more patients that
were further progressed in the disease than any trial had
before.
Mr. Wallach. And that was used against us.
Ms. Abrevaya. And that was used against the company when
they sought approval.
Mr. Wallach. We need to have both players--and implement
the guidance.
Ms. Abrevaya. So we need both players to be true to the
guidance, and implement.
Mr. Pallone. All right. Thank you. Let me just--I know this
time is almost gone, but Dr. Andrews, can you offer any insight
into how trials could be better designed to allow for more
inclusion?
Dr. Andrews. Yes. Our field--actually, in collaboration
with the FDA, have designed something called the platform
trials, actually, which Dr. Cudkowicz leads. And it has
broadened the inclusion/exclusion criteria to allow more
patients or people with--living with ALS to participate in
clinical trials.
The issue is--I think it is true that manufacturers are
trying their best to broaden the inclusion/exclusion criteria.
Many of the drugs that we are testing are trying to slow down
disease progression. And so often, previously, the inclusion/
exclusion was very stringent to get very early onset or early-
stage disease, which meant that more than half of people living
with ALS were not eligible, and that is what led to this kind
of lack of access. And there was no other ways to gain access
to experimental therapies, no expanded access, no open-label
extensions.
And so that, I think, is changing across the field. But, as
Brian and Sandra mentioned, it will take--in order to design
clinical trials that are more inclusive, we will have to employ
technology. So there are ways to stratify populations and
identify subsets of populations that you think might respond
better to that particular drug, but we need the help of our
regulatory colleagues to understand how to employ that in a
clinical trial.
Second, if there is a prespecified subpopulation that would
be your analysis, your primary analysis, they have to accept
that, so that we can include a more broader population.
And so there are ways to design it, but we have--we need
kind of to work together with our regulatory colleagues to
ensure that that would be acceptable to them.
Mr. Pallone. All right. Thank you so much. Thank you.
Thank you, Madam Chair.
Ms. Eshoo. The gentleman yields back. The Chair is pleased
to recognize the gentleman from Virginia, Mr. Griffith, for
your 5 minutes of questions.
Mr. Griffith. Thank you, Madam Chair. I appreciate it.
Dr. Andrews, I am going to start with you. In regard to
ALS, you know, it is supposed to be relatively rare--not as
rare as Huntington's, but relatively rare. And yet I know four
or five people that have had it. Is there any research that you
are aware of that is going on with, like, a geographic
outbreak?
I mean, at one point in time, in about a 4- or 5-year
period, I had 3 people that I knew who had, in their earlier
part of their life, had all lived within probably a half mile
of each other. Is there any work going on on geographic
outbreaks of ALS?
Dr. Andrews. That is a very good question. Historically, in
ALS we have identified populations and specific geographic
areas like Guam, for example, that had high rates of ALS due to
environmental exposures. And over the course of study, there
have been many epidemiological studies looking at environmental
exposures and toxins that may increase your risk of ALS.
It is, actually, from the ALS Association's standpoint, one
of the priorities in studying risk factors, and that is why the
funding to the CDC National ALS Registry is critically
important to identify those clusters.
One of the most important risk factors we have already
identified and acknowledged is the service in--by our veterans.
Military service increases your risk by 2 times the general
population.
Mr. Griffith. Yes, do--is the thought today in--and I know
this may not be directly your area, but is the thought today
that it is--it actually causes it or may just be a trigger for
the onset of ALS?
Dr. Andrews. I think that is still yet to be determined.
But there are definitely exposures that have been identified as
associations.
Mr. Griffith. And I am sorry, I was talking about exposures
to some kind of an environmental----
Dr. Andrews. Yes, those--there have been associations that
have been identified, and warrant further research, and that
could be helped by the ALS Registry.
Mr. Griffith. Now I want to completely switch gears and go
to Huntington's. But I am going to ask you a question, because
it is something I think we need to be looking at, and I don't
know the answer, and you probably don't either. But I am going
to ask the question, because it gives me a good platform.
You said, in regard to ALS, if we knew what caused it, we
could cure it today. We could cure it today if we knew--
understood what caused it. With Huntington's, we know what
causes it, and yet we are still not able to cure it. You got
any comment on that?
Dr. Andrews. Well, I can only speak to ALS as my
specialty----
Mr. Griffith. Yes, ma'am.
Dr. Andrews [continuing]. But, you know, as I said, there
are--ALS also has--in the minority of patients--has a genetic
contributor to their disease. And there are technologies that
can be targeted and deployed for genetic diseases.
Mr. Griffith. Thank you. I am going to go to Ms. Booth. Ms.
Booth, if you would unmute, I could ask you a couple of
questions.
[Pause.]
Mr. Griffith. If you are with me, what I want to know is,
the clinical trial that you were involved in, and now the
clinical trial that your mother is involved in, are those for
drugs to treat Huntington's, or----
Ms. Booth. They----
Mr. Griffith. Yes?
Ms. Booth. Can you hear me?
Mr. Griffith. Go ahead. Yes, ma'am.
Ms. Booth. So let's slow the progression now. There is
nothing to treat right now. But it is to slow the progression
of it now.
Mr. Griffith. So you don't know of any kind of genetic work
that they are doing to maybe figure out how to solve the
problem?
And I bring it up because one of the big successes NIH has
had recently is with sickle cell, where they were able to
completely change the genetic makeup in the blood cells. Now, I
know Huntington's would be more complicated, but I was just
wondering if you knew of any work that involved dealing with
changing the gene that causes this, particularly if we can
catch it before its onset.
Ms. Booth. I am not familiar, but that doesn't mean it is
not the right answer.
Mr. Griffith. No, no, I understand, I appreciate that. I
asked--I have been interested in Huntington's for some time,
because there was a family, now there are two families that I
am aware of in my community that have Huntington's, one of
whom, the first family, was--I was good friends with the
children of that family and knew the mother who died of
Huntington's.
This was all--of course, a lot of this happened before they
had testing available. Your mother, who didn't want to be
tested but always had a happy attitude until recently, with the
onset, I am just curious if any of the data that you have seen
working with the association indicates that there is a higher
rate of suicide for those people who do get tested and realize
they have the disease.
Ms. Booth. I think there is a higher rate of suicide,
because there just isn't--there is no cure, and there is--like,
the only two medicines out there are to treat chorea. Other
than that, it is, you know, other drugs treating the symptoms.
So they get to the point of, like, the hopelessness, or it
gets to the point that, you know, the brain is, like, causing,
you know, mental illnesses and stuff.
Mr. Griffith. Yes, ma'am.
Ms. Booth. So there is a lot higher rate of suicide in HD
patients.
Mr. Griffith. And my time is up, but I am going to ask the
chair, just so I can tell you, just for a couple more seconds,
as a result of your testimony I have instructed my staff to
sign me on to H.R. 2050, which is one of the requests that you
made. And thank you for your testimony.
Ms. Booth. Thank you so much.
Ms. Eshoo. The gentleman yields back. The Chair is now
pleased to recognize the gentlewoman from California, Ms.
Matsui, for your 5 minutes of questions.
Ms. Matsui. Thank you very much, Madam Chair, and I want to
thank you very much for convening this hearing. This has been
one of the most wonderful, enlightening hearings that we have
had in the Health Subcommittee.
And I want to also thank the patients, the caregivers, and
advocates, because your testimony here really does help us, as
we look to make sure that we are doing everything we can to
address the diseases that are involved in what you are having
to do to deal with every single day.
And for me, I just really feel that each one of us could be
involved in our own families, and we know that. And to hear
even the testimony of the caregivers, that is something that
all of us, in whatever way, know that it could be something
that we will be involved in at some time.
So let me just say this. I would like to follow up on an
earlier discussion from the first panel on the use of patient
experience data in drug development and applications to FDA.
Dr. Esham, what steps do developers take to collect patient
experience data, and how is that communicated to FDA?
Dr. Esham. Thank you for that question. So, you know, as
you are very aware of, as part of PDUFA VI and 21st Century
Cures, there was a tremendous effort to really set the
framework to establish a systematic approach to incorporating
patient experience data into the entirety of drug development
and drug review.
I would say we are making tremendous strides in collecting
patient experience data that are very--on a much more regular
basis, provided as part of the application. That could be in
terms of primary endpoints, secondary endpoints, as well as
things like patient preference studies, which provide context
about how to think through benefit and risk. So all of that is
advancing, but we want to advance it a lot more. And so, again,
there is still work to be done.
Another requirement was for when patient perspective data
is submitted as part of the package and reviewed, the FDA is
required to report on that fact. We would like to see that
reporting to provide more context so that we can gain insights,
not just that it was reviewed but what impact did it have on
the review decision making. And that, itself, will help more of
us understand how to develop stronger--collect the strongest
possible patient perspective data to continue to inform
regulatory decision making.
We also want to advance the ability to put this information
in the label, so that it can be communicated to the patients,
their families, and their physicians. So these are things that
I think we still want to improve as we move forward and
continue to develop more----
Ms. Matsui. Could I also ask you that----
Dr. Esham. Yes?
Ms. Matsui. Now, FDA has indicated it may consider patient
experience data differently for different disease types. Do
developers similarly use patient experience data differently?
Dr. Esham. I am sorry, I am not sure I completely
understand the question.
Ms. Matsui. Well, the FDA has indicated they will consider
patient experience data differently for different disease
types. How about the developers? Do they use patient experience
data differently, also?
Dr. Esham. I don't know that it is different, it probably
depends on the--you know, again, if you are trying to support,
say, a benefit/risk decision, whereas some of the patients on
this panel have talked about the value of being able to improve
quality of life, your daily functions, patient perspective data
would be very--is very important, and it will focus on that
question.
So I don't know that it is different, as much as there
might be different questions that are trying to be asked, if
that makes sense.
Ms. Matsui. OK. Let me change here.
Mr. Wallach, thank you for your testimony. In your
testimony you discuss your view that FDA could do more to
consider patient experience in conducting a risk/benefit
analysis. So what is the best way for FDA to approach this
challenge, given that experience--inputs from patients may
vary?
Mr. Wallach. The best way for FDA----
Ms. Abrevaya. The best way for FDA to----
Mr. Wallach. Approach.
Ms. Abrevaya [continuing]. Approach patient-reported
outcomes----
Mr. Wallach. [Inaudible.]
Ms. Abrevaya [continuing]. To proactively work with drug
sponsors to incorporate----
Mr. Wallach. New technologies.
Ms. Abrevaya [continuing]. New technologies that allow us,
as patients----
Mr. Wallach. To provide information----
Ms. Abrevaya [continuing]. To provide information that was
never available before.
Mr. Wallach. And that information----
Ms. Abrevaya. And that information, as Dr. Andrews
mentioned, can help us understand if a therapy----
Mr. Wallach. [Inaudible.]
Ms. Abrevaya [continuing]. Is helping us retain function,
which is everything.
Mr. Wallach. So being more forward leaning----
Ms. Abrevaya. So being more forward leaning is the key
here.
Ms. Matsui. Well, thank you so very much, because I believe
very much that the patient experience is really very, very
important as we look ahead to how we may address these issues
in a more holistic way.
So, Madam Chair, I yield back. Thank you very much.
Ms. Eshoo. The gentlewoman yields back. The Chair is
pleased to--always be pleased to recognize the gentleman from
Florida--from Georgia, Mr. Carter, our resident pharmacist.
Mr. Carter. Thank you, Madam Chair.
And let me begin by thanking you for being here and
thanking those who joined us on--virtually, for your testimony.
Let me just say that your presence here, that your presence
virtually, and that your advocacy brings a human touch to ALS,
to Huntington's, and that is extremely important. I echo the
remarks of my colleague Representative Guthrie when I say that
it is important for you to be here. It is important for us to
understand.
As Chairwoman Eshoo said, I am a pharmacist, and I
practiced pharmacy for over 32 years, and I will tell you that,
through research and development, I have witnessed nothing
short of miracles in the way of medicine. And it has been
extremely important that I continue to encourage companies and
the United States Government, the Federal Government, to invest
in research and development. Because, as I say, I have
witnessed nothing short of miracles in the years that I
practiced pharmacy. And it is extremely important, and it gives
hope. It gives hope to all of us, and it gives it to you. So
please understand that I am--I support you.
Dr. Esham, I want to ask you. In your written testimony you
suggest that investment in therapies and cures for chronic
diseases have been in decline, or is low, relative to the rate
of disease in patients. You even report that funding for
Alzheimer's therapy was 16 times lower than oncology funding,
despite estimates that the disease will impact 13.8 million
Americans by 2050 and cost $1 trillion annually.
My colleagues across the aisle have worked to pass
legislation in H.R. 3 that would upend investment in new cures,
due to revenue reductions from their proposed international
pricing index. The Council on Economic Advisers estimates that
legislation would stop over 100 new drugs from coming to market
over the next decade.
Obviously, we all want to decrease prescription prices, no
one more than I do, having been on the other side of the aisle,
on the prescription aisle. This has been one of my primary
focuses since I have been a Member of Congress. But I just
don't think that this is the way--this is the approach we
should be using.
And I wanted to ask you, Dr. Esham, are you concerned that
such revenue reductions as I described here would further limit
new research into therapies and cures for ALS and other
neurological diseases?
Dr. Esham. Yes, I think that is a fair statement. I mean,
as you point out and as my testimony points out, this is a--it
is a difficult endeavor, fraught with failure and heavily
reliant on venture and public market investment.
We are committed to working with Congress on policies to
help remove or alleviate fiscal burdens to patients, but
sweeping policies that create more uncertainties relating to
the ability to get returns on investment for the less than 1
percent of the programs that actually make it to the market
will unquestionably have a negative effect on future
investment, and impact future innovation.
Mr. Carter. And as you say, these are risky investments
that these companies are making. We all understand that.
Listen, I have seen drugs get all the way up to the final
stage of development and then have to be pulled. And they--and
companies understand this. Look, I am not trying to give the
pharmaceutical manufacturers a free pass here. They need to do
a better job with prescription pricing. But at the same time,
they do play an important role, extremely important role in
research and development in what they invest in that. And that
is something that we have to continue to encourage.
Dr. Esham, you also discussed in your testimony that the
first-ever disease-modifying ALS drug moved beyond phase three
clinical trials for the first time ever this year. But,
unfortunately, 87 programs were suspended over the past decade.
What do you attribute this long-term lack of success to?
And what are the biggest barriers that we face in getting
drugs to treat neurological diseases approved?
Dr. Esham. Sure, and that is a complex answer, but I will
try to just hit the highlights.
Again, you know, Alzheimer's is a--it is a complex disease.
And, as I pointed out, there are, you know, over two dozen, you
know, genes that we have identified now associated with
Alzheimer's.
I will say a lot of the failures in Alzheimer's that is
different than the generality across diseases, they have a lot
of failures in phase one, where you are really doing, like,
early safety studies. They are pretty much on par with phase--
during phase two, in terms of transitioning from phase two and
initial efficacy and safety studies to phase three. But phase
three has where--has been the real brick wall. And so this is a
really exciting time to see the first disease-modifying program
get approved.
And again, when you think about what accelerated approval
did for cancer, it is a great--it will allow us to gain further
understandings, and we do think it will have a positive impact
on investment.
But there are other pathways, as I mentioned in my
testimony, that are in the pipeline that we also have--hold
great promise.
Mr. Carter. Right, right. But research and development is
extremely important. And again, I want to thank you for being
here, and I want to thank those who are participating virtually
for being here. You bring a face, you bring a voice to what
otherwise is just a disease. But it is real, and it impacts
real people. And we must commit to continuing research and
development to come up with cures.
Thank you, Madam Chair, and I yield back.
Ms. Eshoo. The gentleman yields back, and I want to express
not only my condolences to you, Congressman Carter, but that of
all of the members of our subcommittee. Congressman Guthrie
leaned over and just told me that you lost your father. So you
have our sympathies. Those of us that have lost a parent, or
both parents, know how difficult it is, how very, very hard it
is. Really, our lives are never the same again when we lose
those that shaped us, brought us into this world and shaped us.
So we hold you in our prayers and our thoughts. You are a good
friend to all of us, and we really value you here. So God
bless.
The Chair would now like to recognize the gentlewoman from
Florida, Ms. Castor, for your 5 minutes of questions.
Ms. Castor. Well, thank you, Madam Chair, and thank you to
the witnesses. I too have learned a lot over the course of this
very long day, but especially from Yvonne and Kala and Sandra
and Brian. You all are speaking on behalf of millions of other
Americans who don't have the ability to be here and appear
before a congressional committee. So thank you for doing that,
and thank you for sharing your very personal challenges.
Ms. Esham, Dr. Esham, you know, I have read now a former
FDA Commissioner said, when it comes to expanded access, that
oftentimes it is the unwillingness of drug manufacturers to
provide, or sometimes it is just the plain ability of the drug
company to provide a certain drug.
You also cited, in an answer to a question, that it is
difficult sometimes to scale up supply. You also said there are
impacts on clinical trials. Does BIO have an official position
on how manufacturers should approach expanded access, or is it
just too divergent across diseases?
Dr. Esham. We do have principles on expanded access that
largely reflect the points to consider that I outlined in my
earlier answer to the question.
And further, we do have a firm position that the--for our
member companies to comply with the Cures statute, to make sure
that, if they have an expanded access, they provide the
information on their website about whether they have a program
and, if they do, ensure that there is information that helps
patients navigate contacting and working with the expanded-
access programs that are available.
Ms. Castor. OK. Ms. Latty, you provided a very important
voice on behalf of caregivers, so thank you for that. You have
a number of recommendations for the Congress: improve equity in
diagnosis, improve equity in clinical trials.
But we have got to do so much more for caregivers. I note
that you also recommend paid medical and family leave. The
United States of America is the only country, developed
country, that does not provide family medical leave. And it
would just seem, in this day and age, in this country, that we
could support our families across America with paid family
leave.
There--I note--I looked it up, while we were waiting--just
over the course of COVID-19, about 865,000 women have left the
workforce, 260,000 men. So, boy, the burden is--we know it
falls on women, they are doing double duty.
But can you talk a little bit about what caregivers need
today, and your view of family and medical leave?
Ms. Latty. I feel like caregivers need a lot of support.
When you have a family member who comes down with any one of
these horrible diseases, your whole life is completely upended.
And oftentimes, like for someone like me, I mean, like, this
sort of--I had a sandwich generation, where I had kids in high
school, then I have my mother, I am still working full-time. It
was just really out of control.
So you really need some sort of a paid leave, you need
bosses who will understand that you have to take time off
sometimes because things are going on at home with your mother
or your father. You need doctors who are a lot more supportive.
I mean, it is the one thing I learned from my mother's
journey, is especially with low-income people, with people of
color, the doctors are not focused on something as simple as
kindness.
But in many cases, caregiving does fall on daughters. And
oftentimes we are caught between our children and our parents.
And so having a policy of paid family medical leave could make
a huge difference and take off so much pressure, and it also
means that a lot of women wouldn't have to leave their jobs.
I mean, if I didn't have the job I had, I would have had to
stop working because--especially when my mother was first
diagnosed, it was just complete chaos with the hallucinations,
and I didn't know what was going on. And there were just tons
and tons of appointments.
So I really--I kind of, like, just beg you to please,
please help us, help women like me, help men like me, parents
like me, daughters and sons like me.
Ms. Castor. Thank you. Thank you very much. I yield back my
time.
Ms. Eshoo. The gentlewoman yields back. It is a pleasure to
recognize the gentleman from Utah, Mr. Curtis, for your 5
minutes of questions.
Mr. Curtis. Thank you, Madam Chair. Before I jump into my
questions, a couple of observations.
One is how delightful it is to be part of this discussion,
in which it would be hard to find a sliver of difference
between Republicans and Democrats on the committee. And it is
nice to be here, united with all of you together tonight.
The second observation is the clear difference between our
two panels. And it felt a little bit like a lot of resistance
in our first panel and a lot of empathy and sympathy here, in
our second panel. And I would kind of like to explore that just
a little bit.
And maybe, Dr. Andrews, if I could start with you. Like
everybody else here tonight, I have a close friend that is
dealing with ALS. I--we talk about geography. I have a
particular neighborhood that seems to be plagued with ALS.
And this dear friend has had access to a number of
treatments because of his resources to be able to travel around
the world and obtain these. And he frequently discusses how
patients are unable to receive many treatments under right-to-
try and expanded care, and we have talked about that a lot
tonight.
But I kind of want to talk to you about barriers, and maybe
why, some of the root causes of this. I mean, clearly, we
understand the complexity, right, of these clinical trials and
the needs of these pharmaceutical companies. But you mentioned
price, right, as one barrier. And I think we have heard that
message loud and clear.
I am curious. In your opinion, is there another barrier
that we have not really talked about, which is what I would
call the reputation?
So if somebody enrolls in a clinical trial that is maybe
further along in the disease or has other complicating issues,
and the likelihood of a good outcome is less, could there be a
perceived, like, resistance to that, because it is going to
reflect somehow on the reputation of their drug?
And I am wondering if there is anything Congress could do
to help the pharmaceutical companies with transparency, where
that data wouldn't necessarily need to be public. Or is there
another way that we can help them with that perhaps barrier
that they might have?
And is that a barrier, in your mind?
Dr. Andrews. I think it is important to note that some of
the barriers we have already talked about heavily, mainly with
resources, both financially and drug supply from the
manufacturer's standpoint, both expanded-access mechanism and
right-to-try are contingent on manufacturers being able to
provide the product. That is the first thing.
The second, in the instance of expanded access, which is
used more often than right-to-try--and I know right-to-try was
meant to make things a little bit easier to access, but there
are still hurdles like provision of drug, monitoring of safety
at a clinical site, so there might be additional regulations
within a hospital system or an academic center that requires
additional paperwork through the ethics committees or the
institutional review boards.
Resources at the clinical site also are essential to be
able to provide expanded access. Often these are not funded. If
a sponsor is able to provide the investigational product, often
the clinical sites don't get any reimbursement for use of
facilities, or use of any kind of----
Mr. Curtis. Can I jump in on you?
Dr. Andrews. Yes----
Mr. Curtis. Only simply because it is such a limited time.
So what I am hearing from you is still resources is the----
Dr. Andrews. Yes.
Mr. Curtis [continuing]. Single biggest barrier----
Dr. Andrews. Very much so.
Mr. Curtis [continuing]. That you are seeing.
I am aware that there was some experimentation with long-
distance or remote trials. Is that something that we should
expand further, and how big a deal is that?
Dr. Andrews. I think this is a very big deal, especially
for ALS and other, actually, neurodegenerative diseases. As you
heard from the advocate with Alzheimer's disease, access to
clinical trial sites are very difficult. And so anything that
we can do--and I will name some specific issues with it,
because it has been highlighted during the COVID pandemic, when
I have had to conduct clinical trials through the pandemic,
with limited access to our clinical trial sites because of fear
of transmission of the virus.
One is trying to ship investigational product to patients.
Sometimes that can be difficult across State lines, if you are
trying to treat people in a large catchment area.
The second is issues about regulations of principal
investigators or physicians who are doing the clinical trial,
trying to assess safety and monitor the patients, and the
patients may be across State lines. So trying to make it so
that it is easier for patients to participate in clinical
trials in that way.
So shipping of drugs across State lines, practice of
medicine, and research.
Mr. Curtis. OK, as so quickly it happens, I am out of time,
Madam Chairwoman. I thank you. I yield.
And thank you very much for the answers.
Ms. Eshoo. The gentleman yields back. The Chair is
delighted to recognize the gentlewoman--and that she is--from
Delaware, Ms. Blunt Rochester.
Ms. Blunt Rochester. Thank you so much, Madam Chairwoman.
First, I want to say thank you all for your patience. It
has been a very harrowing day here, but it was really important
for me to be present, and I am so grateful. I am so thankful
for you taking the time and sharing.
And I think it was Kala, and then I heard Mr. Carter, and I
heard Ms. Castor use the word ``voice,'' that you are the voice
of millions. And, as I sat here, I recalled losing my father-
in-law to ALS, and we didn't even know for months what was
wrong with him. And it just really reminds me how important our
work, in a bipartisan way, is to the American people and to the
families.
And so I also want to thank Ms. Latty, as she talked about
her mother. I thought about my mother, and how it was her
mother who had dementia, and her mother's mother who would
wander. And just the challenges, watching my great-grandmother.
And I just--I wanted to say, I had a few questions, of which I
can submit in writing, but I wanted you to know how grateful we
are for you standing up and speaking up and speaking out, and I
thank my colleagues, as well, for their leadership on these
issues.
I--Ms. Latty, you mentioned in your testimony--you
mentioned the bill that I led, the ENACT Act, which is really
about expanding clinical trials for Alzheimer's. And I was
hoping that maybe you could talk a little bit about how we
can--first of all, were there provisions in my bill that would
have helped your situation?
And how can we strengthen engagement with communities of
colors, and--color and working families to make sure that there
is an interest in research and clinical trials?
That is my question to you, and I will start there.
Ms. Latty. I don't think there has been much of an emphasis
or energy in reaching out to Latino and Black communities,
explaining that there is help. There is not a lot of
compassion. It is a lot of--lots of people in waiting rooms.
You get moved in to a doctor who doesn't care about you, gives
you the diagnosis, and then your relatives take care of you
until you die. I mean, that is what I saw.
And I think that it is really, really important to start
thinking about how you communicate with these communities, what
kind of messaging, what kind of pamphlets, what kind of
websites, handouts, posters to make the community feel safe and
make them feel that there is hope. Because that was the one
thing that I saw, that just no one seemed to care.
I mean, the only reason I got as far with my mom is
because, you know, thanks to my mom, I got a college education,
and I learned to advocate for myself and for her. But if I was
not me, we never would have gotten into a clinical trial. We
never would have changed neurologists. And God only knows what
would have happened to my mom. You know, the journey is already
really bad. It would have been worse.
Ms. Blunt Rochester. Thank you.
Ms. Latty. So I think messaging, messaging, messaging and
reaching out to the community is really important.
Ms. Blunt Rochester. Thank you. And also, I know the
barrier, as well, in terms of where the research is done and
making sure that we break down some of those barriers.
I also--when Kala was speaking about Social Security
disability--I think today or yesterday was intern day. And I
recalled I was the intern for our current Senator in 1988, and
I went on to be a case worker, working on Social Security
disability. And this is maybe a commercial for families, that
our offices have caseworkers that can help navigate Social
Security disability. That was one of my jobs. And especially
for those who might not have the resources, that is a
commercial.
And then, Dr. Andrews, I was also curious about your
mentioning COVID and the impact of COVID. And specifically, the
two things that you talked about, whether those issues are--in
terms of State--going across State lines, maybe we can follow
up with you afterwards on whether those are State or Federal
problems that are barriers. We would love to follow up with you
afterwards.
I want to end by saying thank you so much, Madam
Chairwoman, again, for your leadership and making this not just
about data, which is important. Science is important, but
people are more important.
So thank you all, thank you very much, and I yield back.
Ms. Eshoo. The gentlewoman yields back. Thank you for your
beautiful remarks.
It is, again, a pleasure to recognize the gentleman from
Pennsylvania, Dr. Joyce.
Mr. Joyce. Thank you, Madam Chair. Thank you for this
important hearing. We are approaching 10 hours that you have
been here, and yet your impact, by coming here to the People's
House, is so important.
Mr. Wallach, I will never forget your words. I want to
present a question to you, and you have presented challenges to
us today. If you had to choose between the problems that we
have addressed, would you look for more innovation, more
accessibility, more flexibility, or more urgency in response?
[Pause.]
Ms. Eshoo. Can you turn your microphone on? We don't want
to miss one word.
Ms. Abrevaya. Yes, the flip answer is that he would choose
all of the above. But----
Mr. Wallach. [Inaudible.]
Ms. Abrevaya. But the most important thing to patients
alive today----
Mr. Wallach. [Inaudible.]
Ms. Abrevaya [continuing]. That they have access to
promising therapies that are moving through the clinical
trial--today.
Mr. Wallach. [Inaudible.]
Ms. Abrevaya. Oh, we look at the European Union----
Mr. Wallach. And the conditional approval pathway.
Ms. Abrevaya [continuing]. And the conditional approval
pathway.
Mr. Wallach. [Inaudible.]
Ms. Abrevaya. And that we have a conditional approval
pathway for animals in the U.S. but not for human beings.
Mr. Wallach. It begs the question----
Ms. Abrevaya. It begs the question----
Mr. Wallach [continuing]. Of why we aren't doing everything
we can----
Ms. Abrevaya [continuing]. Why we aren't doing everything
we can----
Mr. Wallach. [Inaudible.]
Ms. Abrevaya [continuing]. To get therapies to people who
are dying, and to have the science----
Mr. Wallach. [Inaudible.]
Ms. Abrevaya. Oh, to have the chance to live to see a
possible cure.
Mr. Joyce. Thank you for an honest and courageous answer. I
am going to take that answer and pivot to Dr. Esham.
Dr. Esham, the clinical trials process can be long and
incredibly resource intensive, and especially with the delays
that COVID has caused for patients in the clinical trial
process, which really exacerbated what Mr. Wallach just stated.
And he is nodding in affirmation of that.
Are there actions that can be taken or policies enacted to
redesign clinical trials to account for the interruptions that
have been caused by the COVID pandemic?
Dr. Esham. Thank you for that question.
We, at the very onset of the pandemic, we worked with--very
quickly with our member companies to continually engage with
the FDA to make sure that we understood how to document any
disruptions or any missing data that may have occurred due to
revamping operations during the outset of the pandemic.
We currently are operating under the assumption that the
FDA did put out guidance very quickly and put out iterative
guidance over the course of the spring and early summer. So we
were operating under the assumption that that issue should not
result in undue delays in programs. But that is an area that we
are monitoring very closely.
Mr. Joyce. Thank you for addressing what Mr. Wallach put
forth. These delays are so important for these people. Time is
of the essence. Time is limited.
Do you feel, Dr. Esham, that there should be other steps,
such as allowing increased patient access, which Mr. Wallach
just talked about, for investigational drugs outside of the
clinical trials and that we should be mindful of--to account
for the disruptions that have occurred in this pandemic?
Dr. Esham. Again, thank you for that question. And again,
we are supportive of the fact that there is the--that expanded
access is a tool in the toolbox that can--where companies can
provide--can make a decision to provide that medicine,
investigational medicines, via expanded access.
But I do--if I may, I just want to underscore some of the
other revelations that I think are also important in this--in
the entirety of this conversation, and that is, again, some of
the things we learned under the pandemic, and that is how can
we bring the trials, the actual clinical trials themselves,
closer to the patients and in a way that reduces burdens on
patients?
So, in addition to expanded access, I just want to make
sure we are also focusing on improvements to the ability to
enroll people in clinical trials, based on tools and designs,
such as decentralized trials, telehealth, all of those types of
things, in addition to the expanded access conversation.
Mr. Joyce. I think that innovation is so important.
My time has expired, but again, thank you, Madam Chair, for
this incredibly important hearing today, and thank you for
being here at this late hour. I yield.
Ms. Eshoo. The gentleman yields back, and now the Chair is
pleased to recognize one of the new Members to our committee,
and a marvelous addition to the Health Subcommittee, the
gentlewoman from Minnesota, Ms. Craig, for your 5 minutes of
questions.
Ms. Cr aig. Well, thank you so much, Chairwoman Eshoo. And
let me just say that I am new to this committee. This is my
second term in Congress. And this has been one of the most
impactful subcommittee hearings, committee hearings, that I
have been a part of as a Member.
You know, I know, because we meet with our constituents
regularly who have devastating neurodegenerative diseases like
ALS, Alzheimer's, or Huntington's, that this is just a
devastating set of disease states. While I know there have been
huge advancements in our research and understanding of brain
illnesses, I know there are limited treatment options, and
absolutely no cures.
I will add that I know the impacts on families, as my own
family watched my grandfather suffer with Alzheimer's for a
number of years before his passing.
You know, in Minnesota we are so fortunate to have world-
class healthcare systems and research centers like the ALS
Clinic in Hennepin Healthcare. It is the first certified Center
of Excellence in the State of Minnesota, and it provides ALS
patients with the most cutting-edge treatments that are only
available in a research setting. So your words today are
incredibly important to me.
Still, my constituents suffering from those illnesses and
their caregivers do not have the luxury of time. And if there
is anything that you have made clear to Congress here today, it
is that point.
I want to say to our witnesses, and to those in our
communities watching tonight, your message has been received by
this Congress. I am so proud of the bipartisan nature of our
work on these issues on this particular subcommittee. Congress,
NIH, FDA, and industry, we must work together to make sure that
we are doing everything we can to improve patient access to
lifesaving treatments and, ultimately, to cures.
I want to start with Mr. Wallach. Just your presence here
is so commended. Thank you for your patience. Thanks for
sharing your story and advocating not just for yourself but for
everyone who can't be here.
I would like to ask you, from your perspective, what do you
think FDA should do better to incorporate the patient
experience and perspective into their decision making?
Mr. Wallach. [Inaudible.]
Ms. Abrevaya. It took FDA 6 years to write the 2019
guidance that we talked about today. So, at some point in time,
you begin to wonder whether the words are matched by reality.
Mr. Wallach. So one thing--FDA can do----
Ms. Abrevaya. So one thing I think that FDA can do----
Mr. Wallach. [Inaudible.]
Ms. Abrevaya [continuing]. To dramatically expand the
emphasis, and in including patients in their processes, and
finding ways to actually expedite therapies in terminal
diseases--when the risk paradigm is obvious to all.
Ms. Craig. Mr. Wallach, I promise you that my team and I
will make sure the FDA sees the answer that you just gave me to
that question. You and all of our witnesses here tonight have
really touched every single one of us. And for the pieces of
legislation that you have all asked us to review, I commit that
my team and I will do just that.
I just want to close this out, Ms. Latty, by giving you the
last word here. We know that health disparities exist in this
country, especially for Black and Brown Americans. Can you talk
a little bit more about your experience, and how you believe--
what we should focus on to begin to close this gap?
Ms. Latty. Wow, that is such an important question. I think
that there has to be more money put in an effort for Black and
Brown people to participate in clinical trials. I think there
needs to be more outreach. I think we need better medical care.
I think we need paid family leave. I think there needs to be
more visibility, which is one of the reasons why I am so
committed to doing this. I think people need to see my
community, both my Black and Brown community, and see us as
people that are going through this disease in far higher rates
than any other group. I think there needs to be more compassion
and understanding, but I think that the government needs to
focus on finding a cure for Alzheimer's disease. And I think,
by helping Black and Brown Americans, you help all Americans.
Ms. Craig. Ms. Latty, thank you so much.
And Chairwoman Eshoo, thank you for your graciousness in
giving me a few extra seconds. With that, I yield back.
Ms. Eshoo. Any time. And now I think we have exhausted
the--I have recognized all the Members of the subcommittee, and
I can recognize the gentlewoman from Illinois, Ms. Schakowsky,
who is waiving on to our subcommittee.
You are recognized for your 5 minutes of questions.
Ms. Schakowsky. Thank you so much, Madam Chair. So I have
been here--I am in my twenty-second year in the Congress,
unlike Angie Craig, a little bit longer. But I also feel that
this is one of the most impactful hearings I have heard, and I
think it could be a real game changer, the kind of intensity I
hear from my colleagues.
I want to say to people who are listening--you said that
there are hundreds if not thousands of people who are being--
who are advocates, and who are--have ALS--and I remember the
AIDS epidemic, and it--AIDS was a death sentence also. And
actually, it was a population of people--mostly gay men, at
first--that weren't especially popular, necessarily. And yet
the community organized and was out there and fighting and
noisy, and organized groups of supporters and partners to make
things happen. And I think that you probably recruited a lot of
partners, not just ALS, but all the diseases that we were
talking about today. I think there is a lot more intensity of
interest.
I learned, actually, from Mr. Wallach that MS diagnosis--
that ALS is diagnosed as much as MS. Is that true?
Mr. Wallach. That is----
Ms. Abrevaya. That is true.
Ms. Schakowsky. So my guess is, also, that the more money--
that there is more money that goes into MS. People live longer,
et cetera. And it--you know, we may disagree now across the
aisle, but I feel like it is because, in some ways, Big Pharma
gets to pick winners and losers, and maybe the fact that ALS
patients don't live as long, it may not be as useful.
However, I think the government and taxpayers, American
taxpayers, put a lot of money into the research and
development, and trials and all that kind of thing. And
hopefully, as Members of Congress, we are going to be able to
direct more resources and more availability and accessibility,
which, as you pointed out, Mr. Wallach, I think is one of the
most important things--accessibility, especially--as a result
of what you have said today.
And I want to thank all of the witnesses, really. This has
been quite a remarkable hearing. The testimony has been so
incredibly moving. And I mean that in the most active sense,
moving. And I think that we have a lot of assignments that are
out there now of what--the kinds of things that we can do and
that we need to do, and that you will find, in a short period
of time, I think, that you have really made a difference.
I would actually just like to see if you have any final
words, Mr. Wallach, that you want to leave with us, or if any
of the other witnesses have a brief--I have got a little over a
minute left and, you know, just a few closing comments--I would
be welcome--I would welcome them.
Mr. Wallach. Thank the committee----
Ms. Abrevaya. I really wanted to thank the committee for
this hearing, for seeing all of us----
Ms. Eshoo. Put your microphone on, so we can hear it all.
Ms. Schakowsky. And put it close to her.
Ms. Abrevaya. Oh, maybe I need to be closer.
For hearing all of us, for seeing all of us, and for acting
on all the requests we have made as advocates today.
The committee, this Congress, has the chance to end
diseases that were once hopeless.
Mr. Wallach. [Inaudible.]
Ms. Abrevaya. We hope you have the courage to see this
through.
Mr. Wallach. And we look forward----
Ms. Abrevaya. And we look forward----
Mr. Wallach [continuing]. To celebrating----
Ms. Abrevaya [continuing]. To celebrating the end of these
diseases with you.
Ms. Schakowsky. Well, thank you. I am so proud to have you
as constituents of mine. I am honored. And I thank all of the
witnesses. And, you know, we are not powerless here to make a
difference and to partner with you to make them in the right
direction.
So thank you, Madam Chair. I really appreciate it.
Ms. Eshoo. The gentlewoman yields back. And last, but
certainly not least, we will close out the questions of Members
today with the ranking member of our full committee, Mrs.
McMorris Rodgers.
I am glad you could make it back.
Mrs. Rodgers. Well, I heard just the tail end of that, and
I just want to say thank you for being here. Thank you for your
compelling advocacy, for sharing your story.
I was talking with Jan earlier--well, she has talked to me
a couple of times, actually, about this hearing and just what a
long day this has been and the fact that you made the trip, you
traveled here. That is not easy, to be here and to share your
story. And it is powerful, it is powerful.
And we have all been impacted by you and others that have
received this devastating diagnosis with ALS. And I have worked
in years past, but I think this is really an opportunity for us
to come together and to do what you just stated, to really make
a difference. And you know--and I am reminded again of just the
tremendous research that is underway right now, and we are on
the verge of amazing breakthroughs, and we need to say yes and
embrace what it--all that can mean to so many individuals. So
you represent not just yourself, but you are representing a
whole bunch of other people. So thank you so much.
I wanted to ask Ms. Booth too. You know, your family has
faced a lot of challenges, getting your grandfather the best
care possible, and particularly at the end, giving--given the
symptoms he was experiencing. How common is it for HD patients
to receive services in long-term care facilities, and how
challenging is it for HD families to locate a facility that can
provide the appropriate care?
Ms. Booth. Yes, so there are actually only 10 long-term
care facilities that specialize in Huntington's disease in the
United States. So that is a very few. And then, you know,
people are driving hundreds of miles. So it creates, you know,
a lot of frustration. So definitely, we need to work on
expanding that, or also helping, you know, with the--like,
helping people be able to stay home and have care at home as
long as possible.
Mrs. Rodgers. Well, again, I appreciate you spending the
day with us and sharing your story and advocating for so many
others. I think this has been an important hearing for all of
us, and I look forward to working together to continue to
advance solutions that are going to improve so many lives.
Thank you, Madam Chair. With that I will yield back.
Ms. Eshoo. The gentlewoman yields back.
Well, I think that parting is--this sweet company, I think
it is somewhat difficult, because we--there is a lot of
emotional tie between those of us that are seated here and you
that gave the testimony today.
I am proud to have brought this hearing forward. It was
highly intentional, because it was, really, desperately needed.
But you have been the stars. You have been the stars. Every
Member here, every Member, has hung on every word that you have
uttered.
To Ms. Abrevaya, what a wife you are. What a partner you
are. What a mother you are. What a citizen you are. You have--
you are a source of pride to all of us, and it is really
humbling to have you come into our committee room, and that you
would repeat the words of your beautiful husband to the people
of our country and their representatives.
To you, Dr. Andrews, to all of the witnesses that were part
of the second panel, thank you. You have been so instructive to
us. You have taken the very real stories of your day-to-day
lives, really expressing to us what--you know, the very burdens
of humanity in your personal stories, taking care of your
mother, taking care of your husband, and then speaking for all
of the advocates and the patients across the country.
Members know that we speak for, what, some 750,000 people.
You are speaking for millions in our country. And although this
has been an extraordinarily long, drawn-out, frustrating day--
and I know that you are exhausted--but none of it has been a
waste of time. None of it, not 1 minute. Even the waiting is
worth it, and we are going to show you that it was worth it by
taking up the legislation, working together to pass it. I think
that there is a rock-solid commitment here at the committee to
advance this legislation that Dr. Andrews and others, including
the advocates, have said. You have been instructive to us. You
have said, ``This is what we need. It is the right ingredients.
It is the right recipe to address what is ailing us.''
My hope is, more than anything else, is that hope comes out
of this. And I have confidence that it will. I have been around
here for some time. I can feel it. It is in the air. It is
here. And I think that our best work is right at hand. So, as
you travel home, know that you have made an enormous, enormous,
extraordinary difference. Know that, all right?
Bravo to you, Mr. Wallach. Thank you, thank you, thank you.
OK, I would like to--absolutely.
[Applause.]
Ms. Eshoo. All right, to our wonderful ranking member, I
have a request. It is a request for unanimous consent to enter
into the record a--really, a wonderful list of documents from
national organizations, and--I can read them all.
Mr. Guthrie. No objection.
Ms. Eshoo. OK, no objection. Thank you very much, so
ordered. All of these documents will be entered into the
record.
[The information appears at the conclusion of the hearing.]
Ms. Eshoo. We thank all of those that submitted these
documents. We value what is contained in them.
And, pursuant to committee rules, Members have 10 days to
submit additional questions for the record to our witnesses.
And witnesses, we ask that you please respond as promptly to
any questions that you receive.
And at this time, the subcommittee is adjourned.
God bless all of you. Thank you. Colleagues, you have been
spectacular today. It is really an honor to serve with you. And
all of our collective thanks, from committee members to the
staff on both sides of the aisle. You have worked hard. You
have put in many, many hours, and we appreciate it. Thank you,
one and all.
The subcommittee is adjourned.
[Whereupon, at 8:49 p.m., the subcommittee was adjourned.]
[Material submitted for inclusion in the record follows:]
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