[Senate Hearing 119-415]
[From the U.S. Government Publishing Office]
S. Hrg. 119-415
FROM REGULATOR TO ROADBLOCK:
HOW FDA BUREAUCRACY
STIFLES INNOVATION
=======================================================================
HEARING
BEFORE THE
SPECIAL COMMITTEE ON AGING
UNITED STATES SENATE
ONE HUNDRED NINETEENTH CONGRESS
SECOND SESSION
__________
WASHINGTON, DC
__________
FEBRUARY 26, 2026
__________
Serial No. 119-25
Printed for the use of the Special Committee on Aging
[GRAPHIC NOT AVAILABLE IN TIFF FORMAT]
Available via the World Wide Web: http://www.govinfo.gov
__________
U.S. GOVERNMENT PUBLISHING OFFICE
63-835 PDF WASHINGTON : 2026
=======================================================================
SPECIAL COMMITTEE ON AGING
RICK SCOTT, Florida, Chairman
DAVE McCORMICK, Pennsylvania KIRSTEN E. GILLIBRAND, New York
JIM JUSTICE, West Virginia ELIZABETH WARREN, Massachusetts
TOMMY TUBERVILLE, Alabama MARK KELLY, Arizona
RON JOHNSON, Wisconsin RAPHAEL WARNOCK, Georgia
ASHLEY MOODY, Florida ANDY KIM, New Jersey
JON HUSTED, Ohio ANGELA ALSOBROOKS, Maryland
----------
McKinley Lewis, Majority Staff Director
Claire Descamps, Minority Staff Director
C O N T E N T S
----------
Page
Opening Statement of Senator Rick Scott, Chairman................ 1
Opening Statement of Senator Kirsten E. Gillibrand, Ranking
Member......................................................... 2
PANEL OF WITNESSES
Annie Kennedy, Chief Mission Officer, Everylife Foundation for
Rare Diseases, Washington, D.C................................. 4
Jeremy Schmahmann, MD, Director, Massachusetts General Hospital
Ataxia Center, Boston, Massachusetts........................... 6
Bradley Campbell, President and CEO, Amicus Therapeutics,
Princeton, New Jersey.......................................... 8
Cara O'Neill, MD, FAAP, Chief Science Officer, Co-Founder, Cure
Sanfilippo Foundation, Columbia, South Carolina................ 10
APPENDIX
Prepared Witness Statements
Annie Kennedy, Chief Mission Officer, Everylife Foundation for
Rare Diseases, Washington, D.C................................. 34
Jeremy Schmahmann, MD, Director, Massachusetts General Hospital
Ataxia Center, Boston, Massachusetts........................... 41
Bradley Campbell, President and CEO, Amicus Therapeutics,
Princeton, New Jersey.......................................... 45
Cara O'Neill, MD, FAAP, Chief Science Officer, Co-Founder, Cure
Sanfilippo Foundation, Columbia, South Carolina................ 51
Questions for the Record
Annie Kennedy, Chief Mission Officer, Everylife Foundation for
Rare Diseases, Washington, D.C................................. 93
Bradley Campbell, President and CEO, Amicus Therapeutics,
Princeton, New Jersey.......................................... 96
Statements for the Record
ALS Association Statement........................................ 101
Huntington's Disease Society of America Statement................ 103
Jeremy D. Schmahmann, M.D., Statement............................ 115
Little Hercules Foundation Statement............................. 165
Individuals with Rare Diseases' Statements for the Record........ 169
Taxpayer Protection Alliance Statement........................... 452
FROM REGULATOR TO ROADBLOCK:
HOW FDA BUREAUCRACY
STIFLES INNOVATION
----------
Thursday, February 26, 2026
U.S. Senate
Special Committee on Aging
Washington, DC.
The Committee met, pursuant to notice, at 9:35 a.m., Room
216, Hart Senate Office Building, Hon. Rick Scott, Chairman of
the Committee, presiding.
Present: Senator Scott, McCormick, Johnson, Moody,
Gillibrand, Kim, and Alsobrooks.
OPENING STATEMENT OF SENATOR
RICK SCOTT, CHAIRMAN
The Chairman. Good morning. The U.S. Special Committee on
Aging will now come to order. Today we are here to ask a simple
but important question, is the FDA doing everything Congress
intended it to do to quickly get safe, effective treatments to
patients with rare diseases who cannot afford to wait?
For more than 30 million Americans living with a rare
disease, making sacrifices every day is just a part of life,
but something they cannot afford to give up is time. Time means
the ability to walk. Time means independence. Time means being
able to speak, eat, or even recognize a loved one, and too
often, time is exactly what patients lose while therapy sit in
regulatory limbo. Growing up, I saw firsthand how a rare
disease can affect a family. My family didn't have health
insurance, and my brother had a rare hip disease. My mom had to
drive 200 miles round trip just so he could get the care he
needed. She made that sacrifice because care couldn't wait.
My brother couldn't afford to sacrifice time. Congress has
been clear. On an overwhelmingly bipartisan basis we have given
the FDA flexibility to move faster for patients with serious
and life-threatening conditions.
In 2016, Congress passed the 21st Century Cures Act. In
that bill and other bills that followed, Congress gave
direction to the FDA, encouraged the use of real-world
evidence, highlighting that rare disease drug development
requires adaptability and urgency.
These laws are meant to help cut through bureaucratic
delays and give patients access to the care and cures they so
desperately need. Yet here we are, 10 years later, hearing from
patients, physicians, and drug developers that the system is
not working as Congress intended.
I have heard from Commissioner Makary that he is working
hard to fix longstanding problems at the FDA and I want to
thank him for the work he is doing to try and make a strained
system work better for patients. However, advocates here today
will describe inconsistent review practices, shifting
standards, and redundant, often late appearing data requests
that in many cases may not be driven by safety concerns but by
an overly cautious and rigid approach that puts bureaucratic
processes ahead of patients.
As we will hear, the human cost of this regulatory slow
walking is real. Many of the patients affected by these delays
have no other treatment options. Patients from every State come
and talk to our offices, and I am sure the same thing with the
Ranking Member, sharing their irreversible declines in health
that happen while they or someone they care about waits for a
treatment that might never come.
It is heartbreaking to hear from families who are left
watching their loved ones deteriorate, while promising
therapies remain stuck in review. Meanwhile, small biotech
companies struggle to survive years of uncertainty, even when
their science is sound. Beyond individual patients, there are
serious national security consequences that come with the FDA's
inaction and delays.
Our adversaries have been accelerating their drug
development and approval, attracting investment, talent, and
clinical trials. FDA inaction here at home creates an economic
and national competitive issue. Let me be clear, this hearing
is not about weakening safety standards. Safety must always
come first, but safety and speed are not mutually exclusive.
A system can protect patients while still acting with
urgency, transparency, and common sense. Some of you may be
asking why the Senate Aging Committee is tackling this issue
when so many of those impacted by issues with rare disease
treatments are young. Here is why. Part of caring for America's
aging population is making sure that more Americans are given
the opportunity to grow old.
It may sound cliche, but we are all aging. If something is
standing in the way of a younger American making it to their
senior years, it is absolutely the business of this Committee
and something we need to try and fix. It is my hope that
today's hearing will serve as a useful tool to help us
understand what we can do to bring accountability,
transparency, and efficiency to the process.
We are joined by an incredible panel of witnesses here
today representing a wide range of perspectives, but all
working toward a better future for people living with rare
diseases. Now, we have a lot of members in the crowd that are
here because rare disease drugs are very important to them, and
I want to thank everybody for being here. Now, I would like to
recognize Ranking Member Gillibrand for her opening statement.
OPENING STATEMENT OF SENATOR
KIRSTEN E. GILLIBRAND, RANKING MEMBER
Senator Gillibrand. Thank you, Chairman Scott. I really
appreciate you calling today's hearing. Thank you to our
witnesses and the advocates who are here for Rare Disease Day
on the Hill. It makes a big difference that you come together
to make sure your loved ones are being heard and that the
challenges and struggles that you go through as families and
supporters are being understood by lawmakers.
Every one of us in this room today knows that when we have
a friend, or a loved one, or a family member who has a rare
disease, that the most important thing is finding a cure,
getting the treatment, and making sure they survive. A disease
is considered rare if it affects fewer than 200,000 people, but
rare diseases actually aren't that rare. One in ten Americans
is living with a rare disease.
As you know, many of these patients face substantial unmet
medical needs. Because it can be really difficult and expensive
for companies to develop these treatments and the FDA to
evaluate them, Congress has provided the agency with
significant regulatory flexibility to encourage both biotech
innovation and rare disease therapies.
These include authorizing the accelerated approval pathway
to speed up the drug review, establishing programs like the
Rare Disease Endpoint Advancement Pilot to bolster novel
endpoint development, and strengthening and expanding the use
of patient experience data and real-world evidence in drug
reviews.
These mechanisms are designed to help improve access to
novel treatments for our patients, and they are supposed to
provide drug sponsors with a predictable and consistent
approach to addressing regulatory science challenges that are
unique in rare disease therapy development and review, like
designing complex clinical trials, developing appropriate
endpoints, and using real world evidence, but it is not working
how it should be. FDA's approach, transparency, and flexibility
varies widely between its offices, divisions, and centers. I
have seen a pattern of hesitation to use authorized
flexibilities, limited communication with drug sponsors,
failure to incorporate patient experience in real world
evidence reviews, and FDA shifting its regulatory position on
trial design at the last minute, rejecting drug applications,
and requiring new clinical trials the sponsor may be unable to
perform. This is heartbreaking for patients, and it is why we
can't afford delays and disruptions in treatment.
Rare diseases can progress rapidly, cause irreversible
harm, and in some cases premature death. This is also
frustrating for drug sponsors who face increased costs and
delayed timelines that impact the viability of their clinical
trials, particularly in the United States. Uncertainty shapes
behavior across the biotech ecosystem.
Without consistency and predictability, drug sponsors will
continue to struggle with seeking FDA approval and will take
their clinical trials elsewhere, like to China. This is bad for
business, and it is bad for patients. If we want the U.S. to
remain the global leader in biotech and we want American
patients to have access to these novel treatments, things need
to change.
Congress must hold the FDA accountable. We must make sure
FDA fixes its inconsistent and unpredictable application of
regulatory flexibility. It is essential for supporting
innovation, while upholding the highest standard for safety and
efficacy, in the approval of these rare disease drugs.
FDA appears to be moving in the right direction. With the
rare disease evidence principles, the rare disease innovation
hub, proposing new pathways for approval and trying to hire
more reviewers, but it doesn't matter what agency leadership
puts in a press release. It is about execution and
implementation across all levels of that agency. Consistency
from top to bottom.
Congress will ensure that happens by conducting oversight,
encouraging application of authorized flexibilities, and
providing adequate resources to restore agency capacity. I look
forward to hearing from our witnesses and working with this
committee to hold the FDA accountable because rare disease
patients cannot wait.
The Chairman. Thank you, Ranking Member. I would like to
welcome our witnesses, experts who are here to talk about how
serious this issue is and the steps we can take to ensure
patients with rare diseases are not left behind by regulatory
delay. First, I want to recognize Annie Kennedy, Chief Mission
Officer at the EveryLife Foundation for Rare Diseases.
Ms. Kennedy is a nationally recognized leader in rare
disease policy and patient advocacy and works directly with
patients, caregivers, and families navigating the drug
development and approval process.
EveryLife represents the voices of rare disease communities
across the country, and has long advocated for patients
centered policies, regulatory flexibility, and timely access to
life-saving therapies. Thank you for being here, and please
begin your testimony.
STATEMENT OF ANNIE KENNEDY, CHIEF MISSION
OFFICER, EVERYLIFE FOUNDATION FOR
RARE DISEASES, WASHINGTON, D.C.
Ms. Kennedy. Thank you, Chairman Scott, Ranking Member
Gillibrand, and distinguished members of the Committee for
convening this critical hearing. I am Annie Kennedy, Chief
Mission Officer for the EveryLife Foundation for Rare Diseases.
I am honored to be here alongside the hundreds of advocates who
have joined us for Rare Disease Week on Capitol Hill.
Collectively, we are representing the more than 30 million
Americans living with rare diseases. Today, there are more than
10,000 known rare diseases, about 70 percent of which start in
childhood. For small patient communities facing progressive
diseases, time is a commodity.
Traditional large placebo-controlled trials are often
neither feasible nor ethical when considering the challenges
and urgency of rare diseases. Beginning with the passage of the
Orphan Drug Act in 1983, your leadership has provided tools
that have rocketed the U.S. into the most competitive developer
of rare disease products. Each landmark law since has reshaped
our landscape.
In fact, tomorrow marks an anniversary of another watershed
moment for our community here on Capitol Hill. The MD Care Act
hearing convened in this exact same hearing room, presided over
by Senator Arlen Specter, included a 13-year-old named Benjamin
Cumbo. Twenty-five years ago, I watched with great pride as Ben
asked Congress for actions that could help cure him and his
friends so that he could achieve his dreams of growing up,
having a girlfriend, and serving his country.
Congress did respond. In that time, Congress has built a
framework that incentivizes rare product development,
authorizes regulatory flexibility, creates new pathways to
approval, and embeds patient experience into review. While
fewer than five percent of rare diseases currently have an FDA
approved treatment, nearly 1,400 orphan-designated therapies
are now changing the lives of patients and families.
Recently, this momentum has shifted. We are here today
because our community has experienced worrisome trends with
devastating consequences. While we are heartened by recent
announcements of therapy development initiatives, such as the
Rare Disease Evidence Principles Framework and the Plausible
Mechanism Pathway and are eager to work with the agency on
their implementation, our rare disease community has
experienced a series of product application actions that seem
misaligned with these recent public pledges to expand the use
of regulatory flexibility.
Since the start of 2025, we have seen at least 23 complete
response letters declining to approve rare disease therapies,
many under accelerated approval, that suggest a hesitation to
apply regulatory flexibility through surrogate endpoints,
natural history studies, and external controls.
At that same time, advisory committee meetings for drugs
and biologics declined by 65 percent compared to 2024, reducing
opportunities for external expertise and patient insights to
inform complex rare disease product decisions. We asked
families who would been personally affected by recent
regulatory decisions to reflect on their impact. These stories
will be shared for the record. Story after story spoke to
chilling consequences of recent regulatory delays and clinical
trial hurdles.
As one mom shared about her son, Stone. My son is now
receiving this experimental treatment, and he is thriving. For
the first time since his diagnosis, his doctors have told us,
with this treatment, a near normal lifespan is within reach for
a disease that once came with a teenage expiration date that is
nothing short of extraordinary. We are now living in fear, not
because science failed, not because companies stopped fighting
rare diseases, but because of regulatory inconsistency.
We are here today because congressional action is needed to
ensure that this generation of patients will benefit from our
existing rare disease treatment pipelines. We ask that Congress
engage FDA to clarify its approach to accelerated approval for
rare diseases, its consistent application of regulatory
flexibility, and to urge the resumption of advisory committee
meetings so that external expertise informs complex reviews.
We also urge Congress to resource the Rare Disease
Innovation Hub to strengthen cross center coordination and to
establish the Rare Disease and Condition Advisory Committee and
a science focused drug development initiative. In closing, 25
years ago, I stood in this room filled with rare families.
Today, advances in science have put life-altering
treatments within reach for many, but those advances were not
in time for those who were in this with me 25 years ago. While
Ben achieved many of his dreams, he died two days before
receiving his master's degree. We now have the opportunity to
ensure that this generation of rare disease patients will
benefit from today's therapy development pipelines.
Each time a promising therapy faces delays or demise,
investment wanes, future scientific promise is unfulfilled, and
lives are lost. Time is the most precious commodity for our
rare disease community.
As Stone's mom implored while writing from his hospital
bedside, we are closer than ever to rewriting the future of
these diseases. Please don't let my generation become the next
group of mothers who stand at gravesides instead of
graduations. Thank you.
The Chairman. Thank you. Thank you, Ms. Kennedy. Now, I
would like to introduce Dr. Jeremy Schmahmann, Professor of
Neurology at Harvard Medical School, Founding Director of the
Ataxia Center at Massachusetts General Hospital, and Principal
Investigator for the Laboratory for Neuroanatomy. I said that
correct, right?
He is a leading neurologist who treats patients with
progressive and neurodegenerative diseases where time and
access to treatment are critical. He has seen firsthand the
consequences of delayed access to care and the irreversible
loss patients can experience while waiting for regulatory
decisions.
His testimony will round today's discussion and the real-
world clinical impact these regulatory delays have on patients
and families. Thank you for being here. Please begin your
testimony.
STATEMENT OF JEREMY SCHMAHMANN, MD, DIRECTOR,
MASSACHUSETTS GENERAL HOSPITAL ATAXIA
CENTER, BOSTON, MASSACHUSETTS
Dr. Schmahmann. Chairman Scott, Ranking Member Gillibrand,
members of the Committee, thank you for convening this hearing,
and for the opportunity to testify, and for your remarkable
opening statements.
My name is Jeremy Schmahmann. I am the Martha and Robert
Fogelman Chair in Ataxia, and Cerebellar Neurology at
Massachusetts General Hospital, and Professor of Neurology at
Harvard Medical School. I started the first Ataxia Center in
the country, and I have cared for patients with spinocerebellar
ataxias for 45 years.
I am the site principal investigator for Biohaven's study
of troriluzole in ataxia and my comments today reflect my
personal and professional opinion, not necessarily that of my
employer.
Senators, please help us fix the FDA. It has rejected
troriluzole, a drug that is safe--the first treatment to
improve quality of life and slow progression in spinocerebellar
ataxia. My patient Steve, for example, developed
spinocerebellar ataxia type 3, also known as Machado-Joseph
disease, in his late 30's.
Like his mother before him, he will become increasingly
disabled, will need to use a wheelchair, become bedridden, and
die young, but since starting troriluzole a year ago, he has
not changed. Mary, in her late 40's, has type two. After six
and a half years on troriluzole, she has not change.
These inherited neurodegenerative diseases worsen
inexorably and in this business, staying the same is success.
Like other rare diseases, ataxia is difficult to study,
deteriorates slowly, and manifests differently even within
families. There are 15,000 ataxic patients in America. Some
affect hundreds of people, some just a few.
Now, Congress, as you have told us, recognized these
challenges and passed legislation mandating that FDA use
regulatory flexibility and real-world evidence in rare diseases
like ataxia. The drug riluzole, used to treat ALS for 50 years,
was reported to improve ataxia.
Based on this, and the plausible mechanism of action in
spinocerebellar ataxia, Biohaven developed troriluzole, which
metabolizes into riluzole, but is taken once a day with better
brain penetration and fewer side effects. Early in the drug's
development, an ataxic patient who stopped treatment after a
year of open label therapy insisted they go back on troriluzole
because they told us their condition worsened after stopping
the drug.
Biohaven, to their credit, provided troriluzole to these
patients and ran a one-year, double-blind placebo-controlled
study. Patients with spinocerebellar ataxia type three improved
compared to placebo. They were falling less, and they had fewer
injuries. Biohaven requested approval of troriluzole for
spinocerebellar ataxia type three based on these results.
The FDA refused to review the new drug application.
Biohaven obtained FDA feedback and used a revised protocol to
follow patients on drug for another three years, comparing them
with patients in two natural history studies. In this real-
world evidence study, troriluzole showed significant
improvement across nine pre-specified FDA endpoints, slowing
disease by 50 to 70 percent.
This is a dramatic result that was supported by patient and
physician feedback. We were all shocked when FDA denied
approval of this safe drug that makes people better. I wrote
six letters to FDA leadership between 2023 and 2025, co-signed
by 17 ataxia colleagues, asking FDA to review the application
again and work with Biohaven to make the drug available, if
necessary performing post-marketing studies. I never heard
back.
Now, 300 patients, stable on troriluzole, will have to come
off drug, and they are distraught. I met three times with FDA's
Center for Drug Evaluation and Research. On each occasion, they
did not heed the patients or the experts or considered the
science. One panel member said to me, why should I listen to
you?
The FDA's proposed path forward is another placebo-
controlled trial that will take five to eight years, or a
randomized withdrawal of the drug from patients benefiting from
it. If this happens, patients on placebo will die. I believe
this to be unethical, lacking charity, mercy, or kindness.
Senators, please, save our patients' lives. Use your
authority to require that FDA consider real-world evidence and
applies the regulatory flexibility you have legislated, and in
so doing restore transparency, integrity, and competence to the
agency. Thank you.
The Chairman. Now, I would like to recognize Ranking Member
Gillibrand to introduce our next witnesses.
Senator Gillibrand. Thank you, Mr. Chairman. I want to
introduce our next witness, Bradley Campbell. Mr. Campbell is
the President and CEO of Amicus Therapeutics, a biotechnology
company focused on discovering and developing new medicines for
people living with rare diseases.
During his tenure at Amicus, he led the global
commercialization of Galafold, a medication used to treat Fabry
disease in adults, which was approved by the U.S. Food and Drug
Administration on an accelerated basis. Mr. Campbell brings
over 20 years of experience in the rare and orphan disease
fields. You may begin your testimony.
STATEMENT OF BRADLEY CAMPBELL, PRESIDENT AND CEO,
AMICUS THERAPEUTICS, PRINCETON, NEW JERSEY
Mr. Campbell. Thank you very much, Chairman Scott, Ranking
Member Gillibrand, the rest of the Senators on the Committee.
It is my privilege to be here today to speak to you about our
experience in developing drugs for people living with rare
diseases. I am also honored to be alongside my fellow
panelists.
I feel far less qualified than they to speak today, but I
hope I can share some perspectives on the challenges and
opportunities we have to help fix the system. I have had the
privilege to work at Amicus for the last 20 years and have
dedicated most of my professional career to developing new
treatments for people living with rare diseases.
I thought I could begin with a patient story that I think
captures the spirit of the testimony here today and the
conversation we are having. At a recent patient meeting, we
were discussing patient experience data and how we might make
endpoints for clinical trials more meaningful for patients.
During a break, a young woman with Pompe disease took me
aside and said, what would be most meaningful for her is if she
could breathe on her own for just one minute. That would make
the difference between her life and her death. This is not an
approvable endpoint in Pompe disease, of course, but she
depends upon a mechanical ventilator to breathe.
If that ventilator fails, if the battery dies, if an aid
fails to clear a mucus plug, just that 60 seconds of her own
breath could make the different between her life and death. I
think that comment is a very powerful reminder of why patients
and caregivers must help us design better clinical studies with
real endpoints that make a difference for them.
We can't ask patients to wait for years before approved
treatments come when the difference between life and death can
be that single breath. I think the rare disease innovation
ecosystem in the United States has made enormous progress over
the last 20 years, but it must now again adapt in speed,
agility, and flexibility to keep the pace of innovation.
One of our own development experiences at Amicus I think
sheds light on how regulatory flexibility and working together
with sponsors and regulators can make a real difference in drug
development. When we were developing our medicine Galafold for
Fabry disease, we learned in early studies that in some
patients the drug worked and some patients it didn't.
Through careful data analysis and close collaboration with
the FDA and regulators around the world, we developed an assay
that could identify which of the thousands of genetic variants
that cause Fabry disease might best respond to the therapy, and
just as importantly, which ones may not.
The FDA ultimately incorporated that assay into our label
and approved the first ever oral precision medicine for people
living with Fabry disease. What does that mean? That means when
sponsors and regulators work together, the result was an oral
treatment option that has saved thousands of patients' years of
biweekly infusions.
We know rare diseases are biologically complex. We know
they are difficult to study. As we sit here today, 95 percent
of the more than 10,000 known rare diseases lack an FDA-
approved treatment. I think that is statistic many of us are
familiar with, but if you fast forward that pace of
development, it will take us 150 years to only treat half of
the remaining rare diseases.
Small and mid-sized biotechnology companies like Amicus,
Biohaven, and others are the engine of rare disease innovation,
but they can only succeed if the regulatory system adapts along
with unmet medical need. I think there are three practical
areas that we can work together to improve that very system.
First, we must start clinical trials faster. We know in
other countries, those trials start in weeks, not months. We
can reduce administrative requirements, leverage single IRBs,
use AI and other digital tools to get into the clinic faster.
We also must find better ways to measure efficacy. We can use
biomarkers, innovative endpoints, accelerated approvals.
These are things the FDA has at its disposal right now, but
we must use them more and we can make manufacturing inspections
and rules work better. The single biggest delay oftentimes is
inspections for getting patients access to medicines.
The FDA has tools like remote interactive inspections and
relying on global regulators to reduce that inefficiency and
let me close with just one final story. At a patient meeting
last year, a man with Fabry disease told us when he was
diagnosed in his 30's, he stopped saving for retirement because
he thought there was no reason to think he could live that
long. Fast forward 15 years, Fabry disease is now a treatable
disease.
Advancement in treatments have changed that trajectory and
for the first time he is thinking about a future he thought he
would never have. I look forward to working together with the
members of this Committee, and indeed with the regulators, the
broad community here focused on rare diseases to find ways to
ensure that we have a flexible, adaptable, agile regulatory
system that can keep pace with modern innovation.
Thanks so much for the opportunity to testify and I look
forward to taking your questions.
Senator Gillibrand. Thank you, Mr. Campbell. I want to move
to introduce our next witness, Dr. Cara O'Neill. Dr. O'Neill is
the Co-Founder and Chief Science Officer at the Cure
Sanfilippo--the Cure Sanfilippo Foundation, dedicated to
accelerating scientific development on disease and empowering
families with the resources they need to navigate their
journey.
Dr. O'Neill founded the foundation after receiving her
daughter, Eliza, Sanfilippo's diagnosis in 2013. At the
foundation, Dr. O'Neill leads patient focused research efforts
and awareness, working to bridge the gap between scientists,
clinicians, industry, and family.
She was awarded the International 2020 Patient Advocacy
Leader Award by World Symposium for exceptional contributions.
You may begin your testimony.
STATEMENT OF CARA O'NEILL, MD, FAAP, CHIEF
SCIENCE OFFICER, CO-FOUNDER, CURE SANFILIPPO
FOUNDATION, COLUMBIA, SOUTH CAROLINA
Dr. O'Neill. Thank you, Chairman Scott, Ranking Member
Gillibrand, and members of the Committee. On behalf of 15
million children with rare diseases in this country, I thank
you truly for your concern.
I am Cara O'Neill, Chief Science Officer at Cure Sanfilippo
Foundation, a Pediatrician, and mom to Eliza who has an ultra-
rare genetic disease called Sanfilippo Syndrome, or MPS3, one
of many forms of childhood dementia leading to progressive,
irreversible brain damage. I would like to first acknowledge
the critical public service of FDA and its staff who shoulder
complex and heavy workloads every day.
We know the pressures are significant because we feel it
too. Of late, we have seen many press releases highlighting new
FDA policies and programs, which encourage us to look out into
the future with hope, but today, the Committee has called us
here with the recognition that current regulatory barriers are
significantly impacting patients right now, and never more
starkly than for degenerative conditions where time is the most
crucial factor and where every regulatory flexibility must be
leveraged to meet this uniquely urgent need.
We can see this illustrated in a story of three girls with
the same deadly disease, but very different lives. Isabelle, or
Izzy, was the first child with Sanfilippo that my husband and I
met after our own daughter Eliza's diagnosis. Izzy was just 11,
and the disease had already taken a tremendous toll. She could
no longer walk independently, taking only a few steps if her
mom held most of her weight.
Izzy had lost the ability to speak years before and could
no longer eat or drink without choking, so relied on a feeding
tube. She had seizures and increasingly severe abnormal
movements that twisted her arms and legs into painful
positions.
During one visit, Izzy's mom shared that she had come to
accept this disease would take her daughter's life, but what
she said next has always stuck with me. She said, in truth, I
fear her suffering more than I fear death. At that time, my
Eliza was close to four and in an extremely hyperactive stage
of the disease, but she sang and talked with us. She played
dress up and clapped around the house in my high heels. She
rode her tricycle everywhere. She looked so healthy, but what
was going on inside her body and brain was a much different
picture.
Meeting Izzy put us face to face with Eliza's future, the
concrete and cruel reality of what this disease would do. A
medicine didn't come in time for Izzy. She suffered greatly and
passed away just a few weeks before her 15th birthday. For
decades, we have known the cause of this disease. We can
precisely measure the levels of toxic biomarker to determine
whether a treatment is working and now we have the science to
treat it.
Thanks to NIH funding and support from nonprofit
foundations, including our own, a promising gene therapy was
developed and propelled toward clinical trial at nationwide
Children's Hospital in Ohio. While we anxiously were awaiting
news the trial will begin, back at home we watched Eliza's
sentences becoming shorter, her words less frequent. She became
agitated and hardly slept.
The disease was taking hold. Two years later, in May 2016,
the clinical trial finally began and Eliza, then six and a
half, was so very lucky to be the first child to receive that
gene therapy. It was her chance at a life different from
Izzy's--a chance to grow up. Now at 16, it is clear that
therapy changed her life. She surpassed average life
expectancy, runs on the beach, plays in the water, uses picture
cards to tell us how she is feeling and what show she wants to
watch on TV. She can feed herself and goes to school every day.
These are simple but incredibly meaningful abilities that
have a huge impact on her daily life, and children treated with
higher doses earlier in life have even more remarkable
outcomes. Like Caroline, who is now 10. She can read, play on a
softball team, and learn to ski on her recent family vacation.
Despite these breakthroughs and nearly 10 years after the
trial began, families outside the trial are still waiting for
access. Why? Because last summer the drug was denied approval,
not because of safety or how the children were benefiting, but
for questions about manufacturing.
While this is an important issue, FDA could have used its
flexibility to continue reviewing the application while
addressing questions in parallel. You see, early on, trial data
confirmed the drug's mechanism was more than just plausible, it
was biologically effective, showing significant reduction of
toxic biomarker within just six months after treatment in all
the children.
Granting accelerated approval based on this biomarker would
have brought treatment access to children years earlier,
preventing further brain damage and changing the lives of so
many children, like Sadie, who is here today--who is still
waiting. This same drug application was recently resubmitted,
but FDA issued another denial asking for yet more paperwork
before agreeing to review it again.
Congress has given FDA the tools of flexibility it needs to
accelerate approvals for these devastating diseases, but sadly
flexibility and speed are not actually what most rare disease
patients are witnessing.
Transformative therapies are at FDA's doorstep and so, with
great respect, families are pleading for FDA to unlock the door
and move with urgency so that our children can have a chance at
the life they deserve. Thank you.
The Chairman. Thank you for your testimony. Thank you, Mr.
Campbell, for your testimony. Now we will go to questions.
Senator Johnson.
Senator Johnson. Thank you, Mr. Chairman. Again, I have to
commend you for another excellent hearing here. At the start of
the hearing, I received a text from Laura McLinn, who reminds
me that 10 years to this day, as Chairman of Homeland Security
I held a hearing titled, Connecting Patients to New and
Potential Life Saving Treatments. Her son, Jordan, who suffered
from Duchenne Muscular Dystrophy testified at hearing--was
certainly present there.
Two years later, that resulted in Right to Try, which was
not easy to pass. I had to hold up the FDA user fee bill, had
to water down Right to Try quite a bit to make sure that Big
Pharma wouldn't sabotage it. They did sabotage it over in the
House, but because of President Trump's leadership, he forced
the House to pass the Senate version. Its main benefit is its
name. It is very limited in its application, unfortunately.
People have the right to try. Laura has also begged me,
begged me in a text to mention Ataluren and Deramiocel, two
investigatory drugs that are also being held up by the FDA for
Duchenne Muscular Dystrophy. I think we probably are going to
need another piece of legislation, probably Right to Try 2.0--
something that is going to be far more effective than the
current Right to Try, but I will tell you, reading this
testimony this morning, you can maybe tell just by my passion,
it enraged me.
It enraged me that these families, these patients are being
denied effective treatments because of the regulatory
roadblocks. Quick story and again, I want to ask questions, but
a quick story. After I met the Duchenne Muscular Dystrophy
community, they went up before a panel of FDA--this was
probably in 2016, 1917, or 1918--begging. There are about 60
Duchenne Muscular patients' families begging the FDA, please
approve this investigatory drug for our children.
Again, time is muscle, time is brain and that panel, I
don't know who sat on it, listened to those 60 families begging
them and said no, just like they said no--and I can't even
pronounce these diseases and drugs. They say no time and time
and time again. That has to change. Congress is directing the
FDA, be more flexible--say yes.
You know, these patients understand the risks. They ought
to have the right to try. Dr. Schmahmann--am I pronouncing that
right?
Dr. Schmahmann. Yes, sir.
Senator Johnson. I don't want you throwing anybody under
the bus because I don't want this to impact future approvals
but describe your meetings with CDER. To me, it is shocking to
have one of those members of that panel say, why should we
listen to you? Well, because you are a doctor at Harvard.
You are treating patients. You are having success. You are
giving them a new lease on life, and you have got bureaucrats
inside these agencies saying, why the hell should we listen to
you? I want you going into greater detail--describe what those
meetings are like.
Dr. Schmahmann. Thank you, Senator. We have heard a few
words a few times. Heartbreaking as the experience of patients
and families going through this and the compassion that is
required.
I saw none of that in the three meetings with the FDA. The
members of the panel were like talking to a brick wall. There
was no engagement, no dialog. In fact, they said as much, this
is not a dialog, this is not a collaboration. They do not seem
to see the suffering of the patients, and they didn't hear the
science.
They were rigid and inflexible and unyielding. The FDA
worked with the company initially, but then they changed their
mind later, and so, as the studies unfolded, everything came to
a grinding halt. This drug in particular is safe. It
metabolizes into a drug that has been there for 30 years in the
market and is safe. Patients say it works. The doctors say it
works. The study shows it works.
The double-blind first study showed it worked. The real-
world evidence shows it works. Patients behind me, every one of
them, talking to them yesterday, say it works. This drug works.
To paraphrase the Senator, what is their problem? My
experience of the people on that panel, three times, as a
private citizen coming for the first time to the FDA, was
deeply distressing.
Senator Johnson. I have already texted Dr. Tracy Beth Hoeg
and told her I have read your testimony. I will be sending her
your testimony. I hope she listens to this. If I could just
take a couple more minutes, Dr. O'Neill, you are obviously
personally impacted by this.
Can you describe any meetings you have had similar to what
we just heard? Again, the American people need to understand
what these regulators are doing and not doing. Dr. O'Neill.
Dr. O'Neill. Thank you. You know, I will say that my
interactions with regulators have been kind, so maybe a bit of
a different perspective is they have listened. They have been
interested to hear what we had to say. To hear the patient
perspective. I think where we are challenged is that we don't
see that translated into regulatory action.
Some of the decisions that are coming out are not
benefiting patients right now. Listening is great, but two-way
conversation and collaboration is actually what is needed, and
greater transparency in how patient experience data and patient
input is actually being integrated into these decisions.
Senator Johnson. My guess is that panel for Duchenne
Muscular Dystrophy back in 2017 or whatever probably listened
very nicely to the families, but they still said no. That is an
unacceptable answer.
Again, you have my commitment. I am going to delve into
this. We are going to right these wrongs. Thank you. Mr.
Chairman, this is again an excellent hearing. We have got to
followup on this. This is just completely unacceptable. Thank
you
The Chairman. Thank you, Senator Johnson. Senator
Alsobrooks.
Senator Alsobrooks. Thank you so much, Chair Scott. Also
Ranking Member Gillibrand. I am so grateful to be here today
joined by so many patient advocates, caregivers, family
members.
I have heard from many Marylanders living with rare
diseases and from their families, including dozens who have
visited my office this week to share their priorities and their
concerns. As I underscored with the NIH Director a few weeks
ago, patients suffering from devastating diseases do not have
time to wait for needless delays to critical cures. For
Marylanders with rare diseases, delayed access is not just an
inconvenience, it is a matter of life or death.
For many with rare conditions, clinical trials are their
last and best hope. These patients also depend on a regulatory
process that is science driven and capable of turning research
into real treatment. Instead of strengthening those
foundations, this Administration is constantly disrupting
clinical trials, slowing innovation, and undermining the
pipeline to cures.
Scientific integrity should always guide decision-making,
and we must protect the firewall between the Food and Drug
Administration and political influence. President Trump and
Secretary Kennedy continue to decimate critical parts of that
system. The instability they have caused ripples across
families, physicians, researchers, and innovators, and patients
pay the price.
Ms. Kennedy, I would like to ask, over the past two weeks,
we saw a striking example of political interference at the FDA
involving a seasonal mRNA flu vaccine from Moderna. The agency
first declined even to review the application, then reversed
course just one week later after revised regulatory approach.
The abrupt change raised serious concerns about
transparency, predictability, and political influence in what
should be a scientific process. An episode many have described
as regulatory whiplash. What does that kind of volatility
signal about how the FDA is functioning right now, and why does
that matter for rare disease reviews that depend on regulatory
consistency?
Ms. Kennedy. First of all, thank you so much, Senator, for
being here and for all of you being here today, and for this
important issue. I think first it is important to say that I am
not an expert in vaccines, and I am here really to focus on
rare disease, but I appreciate the question really asking about
the trends that we are seeing and us being here really trying
to follow the trends and understand what that means for rare
disease.
I also agree with Dr. O'Neill that we have seen real
intention from career staff and staff scientists at FDA around
their engagement, but what we are concerned about is, to your
question, what seems to be reversals in decisions, where there
had been previous agreement, previous work with sponsors that
was directing sponsors to move in one direction, and then
regulatory decisions seemed to be yielding different decisions
at this point.
As I stated in my testimony, we have seen recently 23
complete response letters issued in rare diseases that are
delaying access to the patient community and having devastating
consequences to our community. Many of those actually are
decisions that are reversals in regulatory agreements that have
been made previously.
Additionally, we are very concerned that previously, if
there were to be a complex decision that needed to be worked
through between a sponsor and the agency, an advisory committee
would have been convened, and we have seen 65 fewer advisory
committees convened in 2025 than 2024.
In fact, none since July. We are very concerned that the
regulatory tools that are at the disposal of the agency to
really work through some of these really complex decisions
aren't being utilized.
Senator Alsobrooks. Thank you. Just very quickly, if I can
also go to Ms. O'Neill. Finding new cures doesn't happen
overnight, and it rarely happens in a single year.
Breakthrough therapies are built over decades of careful
scientific work and discoveries, and NIH funded laboratories
form the foundation for treatments that later move into
clinical trials through regulatory review and ultimately into
patient care.
When NIH research capacity is disrupted, as we have seen,
and weakened, how does that set back the search for new cures
long before therapies ever reach the FDA?
Dr. O'Neill. Thank you for your question. The NIH is a
critical source of funding for innovation in this country and
scientific innovation. It is interesting that when there were
disruptions and uncertainty in the funding, we received a flood
of requests about funding from our small non-profit foundation.
I think non-profit foundations across the country were seeing
that and, you know, we are not equipped to take up all of the
pre-clinical and transformative science that NIH can do. The
role of the NIH in supporting innovation is huge.
Senator Alsobrooks. Thank you.
The Chairman. Thank you, Senator. Senator McCormick.
Senator McCormick. Thank you, Mr. Chairman and thanks to
you and the Ranking Member for convening this and thank you all
so much for being here today to help bring some of these
critical issues to Americans and Pennsylvanians to light. Ms.
Kennedy, more than 30 million Americans live with rare
diseases, yet fewer than five percent have an approved
treatment.
As you mentioned, since early 2025, the FDA has issued at
least 23 complete response letters for rare disease therapies,
while advisory committees use has declined dramatically. When
late-stage rare disease applications raise concerns, what
alternatives to issuing a complete response letter should the
FDA use, including advisory committees or structured post-
approval commitments, to resolve issues without restarting the
entire process?
Ms. Kennedy. Thank you. We appreciate that question. FDA
has at its disposal, thanks to Congress, many types of
engagements between sponsors and the agency. Many of those have
been made possible thanks to the user fees.
We are concerned that many of those meetings and meeting
types aren't occurring, and that the CRLs are being utilized as
a way to perhaps maybe even clear the docket or create delays.
There could be a lot of reasons why that might be happening,
but there are meeting types that have been implemented that
could enable engagement to answer questions that sponsors, and
the agency might have.
We saw actually the agency deploy this during the pandemic,
the COVID pandemic, where we saw real rapid, real time
resolution to a crisis in our country and the agency was able
to interact with sponsors. Get questions answered in real time
and then we saw that CBER tried to operationalize that in other
places and spaces.
We would really, as a rare disease community, like to see
that operationalized within rare disease because we believe
that our rare disease community has the urgency and unmet need
that matches that of a pandemic, of a crisis.
We have individuals in this room who have very limited life
expectancies. If we don't address what is happening in rare
diseases with that same sense of urgency, they would not be
here with us if we were to convene this hearing another year
from now.
Senator McCormick. Thank you. Thank you for highlighting
that urgency, and I think we feel it, and you are helping us to
feel it. Thank you for that. Mr. Campbell, just on the issue of
accelerating the process.
I was taken by the fact in preparing for this that some
countries are moving much faster on rare disease therapies. The
European Union's FAST-EU program caps multinational clinical
trial authorization at 70 days. Australia allows many trials to
begin almost immediately after an ethics approval.
What is going on here? What will happen if the United
States fails to keep pace? What policy changes should we
consider in the Congress, given what appears to be a much more
streamlined approach in other places?
Mr. Campbell. Thank you, Senator. I completely agree. I
think, you know, the United States has been the beacon of
biotechnology innovation for so many decades, and it is part of
why we have more therapies approved today for rare diseases
than we did, you now, decades ago.
I would acknowledge legislation like the Orphan Drug Act
that led to that. As we said in our testimony and many of the
panelists here today, we have now stopped keeping pace with
innovation and I think one exact point, which I raised in my
testimony as well, is speed to clinical trials. For me, on the
one hand it is time for patients, and taking weeks, 70 days,
would be a remarkable number.
I think Congress could work with the FDA to pass
legislation to encourage, again, centralized IRBs, leveraging
digital technology and artificial intelligence to help us do
that. Reducing regulatory requirements. For sure, those things
could speed us into the clinic. The other piece, I think, which
is sitting behind this is our national competitiveness and in
some ways our national security.
When we think about Australia, we think of Europe,
collaborative nations, etcetera--there are other nations out
there that perhaps we see in a different way, and from my
perspective, whether you think of that as a security threat or
whether you think of that as a threat to getting drugs to
patients, in either case, I think Congress can take a
leadership role in helping the FDA to speed through that
process.
Senator McCormick. Thank you all for being here.
The Chairman. Thank you, Senator McCormick. Senator Kim.
Senator Kim. Thank you, Chairman. Thank you to all of you
coming out here. A couple words I just heard that I think
really just hit the nail on the head. I would love your
reactions to it. When we are talking about all the different
problems that we are facing with the FDA, the bureaucracy or
the workforce issues, I think the word that really hits it home
is urgency.
I heard you use that. You know, I heard use that Ms.
Kennedy. I feel like that is really what we are talking about
here. Is like we need a government that is moving at the speed
of urgency that the parents are trying to save their kids,
right. Like, that we are struggling to understand what the
actual purpose here is and the speed with which we need to
move. Look, I got two boys. I got an eight-year-old and a ten-
year-old. I would do anything for them, you know.
I just like, how do we translate that into the urgency of a
government trying to be responsive? I think that is where some
of the disconnect hits on so many levels. You know, Mr.
Campbell, you talked about it. You used the word national
security. I used to work in national security. I was in
Afghanistan and Iraq and elsewhere.
I saw this government move with urgency when they felt like
lives were on the line, but like, why is it that we can't
necessarily translate that to another circumstance where there
are millions of lives on the lines and people just don't have
the time to wait for this? I think that that is really a
purpose. How do we talk about this as a national security
priority?
The same reason we are trying to save lives abroad is the
same reasons we are trying to save the lives here at home. Does
that make sense to you, Ms. Kennedy? Am I kind of grasping the
crux here of what we are trying to push forward?
Ms. Kennedy. Yes, Senator, you absolutely are. Congress has
recognized this urgency in statute and has enabled the use of
regulatory flexibilities, and that is what is reflected in the
accelerated approval pathway and the use of surrogate outcome
measures and biomarkers in clinical trial design in rare
disease.
What we are concerned about is that in many of these
complete response letters, what we are seeing reflected is FDA,
especially in one of the medical product centers, CBER, seems
to be the trend that we are detecting backing away from a
comfort level or use of the surrogate biomarkers.
What we have seen in rare disease is surrogates work.
Surrogate biomarkers do save lives. We have more than 250
products that have been approved through the accelerated
approval pathway, but fewer than 20 percent of those are for
the non-oncologic, non-infectious rare diseases.
Which means there is a distinction between what is
happening in the rare community that is in this room and the
broader rare community. It is really important when we look at
those statistics that we sort of look at what the different
medical product centers are comfortable with and are doing, and
that is why we--we know that the tools are available. We want
to ensure that they are being utilized.
Senator Kim. Mr. Campbell, I wanted to bring you in on this
because, you know, you have talked about this at length. Build
off of what we just heard. How would expand use of adaptive
trial designs or surrogate endpoints by the FDA lend itself to
achieving better outcomes when it comes to rare disease
approvals?
Mr. Campbell. Yes, I think the first step is just use what
we have available to us, right. If you look at oncology, I
think in 2024, there were 8,000 different therapeutics in
clinical trials that dwarfs the number in rare diseases today.
I think a large part of that is the much more welcoming use
of accelerated approval and surrogate biomarkers. Our own
product, Galafold, was approved on a surrogates biomarker. The
competitor product also, Fabrazyme, was approved on a surrogate
biomarker and these things work. I get it, you know, rare
diseases are biologically complex.
It is very difficult to understand how long it is going to
take. You can't do randomized control studies in the same way
you can with broader disease populations. When it is done
right, as in the case of Fabrazyme, 10 years later, after using
real-world evidence and a registry, they are able to confirm
the original surrogate endpoint, and now it is a fully approved
product. For me, the tools are all there. It is really more, as
we have discussed, consistency and using the tools that exist.
If we were to--oh please, go ahead, Senator.
Senator Kim. I just want to jump in here at the end. I mean
the urgency on the trials and moving up forward on the
approvals, but Mr. Campbell, I also want to raise another
issue, which is just how long it often takes to build
manufacturing facilities here in the United States.
You know, the level of slowness with the inspections
themselves. I want that urgency on a manufacturing side as
well. You know, what can you be showing us about the
decisionmakings that manufacturers are going through especially
in terms of being able to build this and manufacture this here
in America.
Mr. Campbell. Here at home. Thank you so much for the
opportunity to address that, so just by background, Amicus, we
work with external manufacturers. As a small cap company, we
don't have the capital to build our own manufacturing
facilities, and we certainly don't have an environment to be
able to do that.
We work outside the United States. It takes three to five
years to just to build a state-of-the-art manufacturing
facility for protein therapeutics. It takes another one to two
years then to get that facility inspected. You are talking five
to seven years from when we want to do this to when it actually
has medicine coming off the line for patients. In my mind, it
is mutually beneficial to all of us, so create incentives--and
they don't have to be financial incentives. Help with
permitting. Help with inspections.
Give priority to inspections for homegrown manufacturing
facilities. Create an environment that is actually supportive
of bringing manufacturing at home, versus using, which is what
we have seen over the last couple of years, more sticks to try
to prevent--probably a more qualified person to speak to this,
speaking in background. Let's use incentives instead of sticks
to encourage that because I think the United States ecosystem,
the patients, all benefit from doing that.
Senator Kim. Mr. Chair, you know, we have talked at length
here in this Committee about the benefits on so many levels of
having that manufacturing here in America, the speed with which
we can move, the capabilities.
You know, these are some very concrete things that I hope
we can followup on and really come up with a game plan here
because it is just, honestly, it is just pathetic that we are
just not able to do this with a greater level of speed given
the skills and the talent and the resources of our country. We
can and should be doing better.
Thank you for holding this hearing today.
The Chairman. Thank you, Senator Kim. Senator Johnson, do
you have some more questions?
Senator Johnson. Yes. Thank you, Mr. Chairman. I mean, I
think the elephant in the room here is, so we have got the laws
in place. They maybe could be beefed up, but I think it is a
personnel issue, right. I fear that not even necessarily the
heads of the agencies, but possibly bureaucrats that have been
there for decades, for whatever reason, they don't like a
particular drug, and so they are able to sabotage it.
My question, how can we overcome the inconsistency from,
you know, one bureaucrat to the next bureaucrat, changing
administrations, or quite honestly, you know, a particular
bureaucrat that has been in there for decades that just keeps
blocking things. I mean, how do you get to the personnel issue?
I will start with you, Ms. Kennedy.
Ms. Kennedy. I think my experience differs from some on
this panel in that we have seen great examples of models where
we have had public meetings and public workshops where FDA has
come together with the patient community, which I think is an
incredibly important mechanism, to have meetings where we can
have regulatory agreement around the use of certain innovative
models in clinical trial design, surrogate endpoints, natural
history studies as a control arm that had then allowed those
programs to move forward.
Senator Johnson. I pointed out in a meeting like that, a
panel, for Duchenne Muscular Dystrophy, 50 to 60 families, and
they still said no.
Ms. Kennedy. I love that reference. What you may not know,
you probably don't know, is prior to being with the EveryLife
Foundation, I was with the Duchenne community, and so that may
have been an advisory committee.
Senator Johnson. Were you in that meeting?
Ms. Kennedy. Yes, I was. Well, it depends on what meeting
you are referring to. If it was an ADCOM, an advisory committee
meeting, that advisory committee did vote no, but then the
agency brought that internally and then overruled that.
Senator Johnson [continuing]. overruled it.
Ms. Kennedy. That is a perfect example of the agency still
has the authority to make the decision because they heard from
the community and what we are concerned about right now is that
the agency isn't engaging with the patient community.
Senator Johnson. Dr. O'Neill, in your testimony you talked
about, you got your CO, the complete response letter. I mean,
perfect bureaucratic type of--in other words, the no letter,
right, and you got the no letter, not necessarily because of
safety or lack of efficacy. It was because there is something
in the manufacturing process, which again, a manufacturer, I
understand that, but can you explain that. It seems like a
pretty weak excuse where you could, we will fix the
manufacturing process so this drug can be made available just
talk about that
Dr. O'Neill. Thank you. I am not an expert on gene therapy
manufacturing, so I will say that. However, the sponsor was
very transparent in reviewing the full CRL with our community
so that we could understand truly what the concerns were. Many
of them were noted to be things like a crack on the floor not
in the manufacturing area, or a tarp that was out back, or
things that really are unrelated to our children.
Senator Johnson. Trust me, I have been through audits. I
supplied packaging material for medical devices. You can find
an excuse to, you know, write something up, pretty flimsy
excuses.
Again, that is my concern. Dr. Schmahmann, in your case, it
was based on real world evidence. It seems like the real-world
evidence was completely in favor of allowing patients access to
this drug. Talk a little bit about, you know, why you got a
CLR, a no letter.
Dr. Schmahmann. Thank you, Senator. You know, one of the
thoughts that came to me as we are going through this whole
process and hearing what happened to Sanfilippo with the crack
in the floor in the factory is that this is a policy of death
by technicality. These little, tiny glitches that the FDA is
producing land up not approving drugs and patients die as a
consequence.
I am glad to hear that there are people in the FDA who are
doing what Congress requires them to do, but that speaks to the
unpredictability and the erratic nature of the responses and
the performance of the people in FDA. There are many ways to go
forwards to use clinical trials and then use the new technology
to bring treatments to patients faster that are safe and make a
difference.
Science advances. The regulation is keeping up with the new
advances, but it seems like the FDA is having trouble with
that. The FDA must keep pace with the updates in science using
the biomarkers, serum or imaging, using digital markers, using
patient reported outcomes.
I developed the patient reported outcome measure for
ataxia, understanding what patients are saying. The key issue
here is that the real experts are the patients. The patients
are the experts by experience. The patients are our research
collaborators. We are all patients. Every one of us has
something.
We are all patients. It may not be a rare disease, but this
applies to us. We are talking about us, whether it is a rare
disease or not. The approach that can be taken, including what
was started at our institution, I think called a platform
trial, where you can have one small group of controls and a
number of other patient cohorts trying different drugs. There
are innovations both in the clinical trial design and the
biomarker space.
This is where we need to move, and the urgency is exactly
what Senator Kim was talking about. There is an urgency now and
some of the drugs on the table now, the ones you have heard
about from Dr. O'Neill and myself, these should be approved
this week. There is no reason not to.
Going forward, we need to find a way to enhance, to
expedite, and make this a better process and have a sense that
when you are going to the FDA, you know what you are getting.
It is not just a random scatterplot of who is going to get what
kind of a person there.
Senator Johnson. Isn't another root cause here is literally
the doctors are no longer at the top of the treatment pyramid?
They have been replaced by regulators. You talk patients are
number one, but doctors are the ones that are most
knowledgeable in this equation, and you are shutting off to the
side. What you are saying doesn't count because the regulators
have replaced you in terms of making these decisions for
patients. Isn't that a big problem?
Dr. Schmahmann. You know, Senator, on your wall in your
office yesterday, I saw your mission statement, which was
triple, teamwork, respect, integrity, professionalism, loyalty,
and education.
The FDA is not doing that. It is the opposite.
Communication, dialog, teamwork between the physicians, the
patients, the pharma who make the drug, the regulators, that is
a two-way street. It is a dialog. In medicine, when we do
rounds in the morning on our patients in the hospital, there is
a discussion.
The physician is there, the residents are there, the nurse,
the nurse practitioner, or the physical therapist, the patient
and the family. It is a conversation, a discussion. This is not
what we are hearing from across the board and certainly from
the other rare diseases. We are here, the few of us.
Turns out there are 30 million people behind us, as you
said. What we are bringing to you is the plea to make the FDA
what it was supposed to be, which is what you regulated, and
allow us to work in a collaborative manner across the board,
not with this kind of hit or miss approach as to who you are
going to get on a committee. You are looking for
accountability.
In fact the leadership of the FDA, it is their
responsibility to hold the feet to the fire of the people under
that person's leadership. Not just to say good things, but to
actually make them happen and bring new drugs to the American
population including us, our patients, my patients, that are
safe and effective.
Senator Johnson. Again, thank you, Mr. Chairman. I think
this is an excellent hearing, excellent testimony. Both you and
the ranking member, you pretty well diagnosed the problem here.
I mean, in your opening statements, you laid out the problems.
This is eminently fixable, and we have to fix it. Again, I am
committed to working with you to do so but thank you for this
hearing.
The Chairman. Senator Gillibrand.
Senator Gillibrand. Thank you. In 1972, the Federal
Advisory Committee Act established advisory committees within
the FDA to help provide independent expert scientific input on
product reviews and policy topics.
In 2025, FDA canceled many advisory committee meetings and
indicated that it would like to move away from involving
advisory committees in the review of drug applications. For
each of the witnesses, you can start Ms. Kennedy, how important
is it to the rare disease community for FDA to restore the use
of advisory committees?
Ms. Kennedy. It is everything. We yesterday had one of our
communities showcase in front of close to 800 members of the
rare disease community how an advisory committee meeting helped
inform a key regulatory decision for the VAR syndrome community
by showing how an open public hearing enabled members of that
community illuminate the nuance of a very complex regulatory
decision in a very complicated regulatory review.
As Senator Johnson just highlighted, I have been a part of
many advisory committee meetings for communities, including the
Duchenne community, and advisory committees don't always vote
yes. That is not the point.
The point is for external experts, including clinicians,
including those with statistical expertise and manufacturing
expertise that are not always internal to the agency, to be
brought to bear on regulatory decisions because we realize that
with 10,000 rare diseases, it is not possible for FDA to always
have all of that expertise internal.
Those committee hearings must be at the avail of the
agency, but also those open public hearings must be available
so that patient communities who are participating in clinical
trials can share what their experiences in those clinical
trials are. One of the challenges we have in clinical trial
design is we don't always know what we are going to find when a
clinical trial begins.
We design a clinical trial hoping that we are going to be
able to select the best outcome measures, but sometimes patient
communities who participate in those trials experience other
benefits and those hearings enable us to hear from patients
about what other outcomes were achieved so that we can make the
best decisions possible for the patient community around safety
and efficacy.
Eliminating those hearings eliminates the chance for FDA to
make the decisions that are in the best interests of the
patient communities possible.
Senator Gillibrand. Dr. Schmahmann and Dr. O'Neill,
congressional actions have advanced how patient experience data
is included in the development and evaluation of rare disease
therapies. What is the importance of the patient voice in this
regulatory process, and what more is needed to ensure FDA
includes this information in its decisionmaking?
Dr. Schmahmann. I agree that it is critical, Senator. I
think that there is a deeper problem. If you don't listen to
somebody else's advice in a complex story, that is the opposite
of humility. It is a denial of the patient's humanity and it is
sort of hubris. You don't want to hear what the patients have
to say? Who are you? That is the problem.
This is all about the patients. To deny the patient voice
in drug development and in drug design--and I agree completely
with Ms. Kennedy here. Determining the end point when you start
is fine if the disease is well known in the millions of people.
In our case, for example, the spinocerebellar ataxia, the
first clinical trials that Biohaven did in the 2016s, we didn't
know what would change. We had to take a guess and I worked
with them in devising the scale, devising a trial. The patients
then told us, you know what, I am falling less, I am not as
fatigued, and my speech is better. There was a different
outcome we didn't understand at the beginning. That is the
epitome of regulatory flexibility.
There is a rule in medicine, listen to the patient, they
are telling you the answer. The second piece is, ignore the
patients at your peril. What we have here is denying of the
patient's story. It is the peril not of us, but of the patient
because now the drugs are not being approved.
I think you have hit the nail on the head here. If you are
ignoring the patient, then why are you getting up in the
morning and coming to do the work that you do with the FDA?
Senator Gillibrand. Well said. Dr. O'Neill.
Dr. O'Neill. Thank you. You know, obviously you have heard
that patients are not outside of the drug development process.
They are critical to it and advisory committees, as Annie had
mentioned, are an important place where we can have that
scientific dialog and hear from patients.
Their experience is also science. It is human science. The
interaction needs to come way before that, because by the time
we get to an advisory board, tens of millions of dollars have
been spent, maybe a decade has gone by. We have not treated
potentially that many patients who needed treatment.
Having a true collaborative dialog early in the process is
essential and something--an opportunity that needs to be acted
upon within the FDA. I think one other thing that we are
understanding is key insights around risk tolerance. We also
want safe medicines, but we also want the opportunity to save
our children because those answers about a clinical trial come
way down the road.
As Mr. Campbell explained, real-world evidence, post-
marketing disease monitoring programs, this is where we need to
be really focusing on these innovative ways. Maybe not so
innovative, honestly, anymore, but more frequently used and
supported ways to provide that longer term evidence to support
accelerated approval.
Senator Gillibrand. Mr. Campbell, did you want to add?
Mr. Campbell. For sure. I think what we keep coming back
to, and I think you hear the theme, is you have all the tools
in place. You have the advisory committees. You have
accelerated approval pathways.
I think the frustration is when they are deployed
inconsistently and without clarity from the sponsors and from
the patient community and from the physicians in terms of how
you end up, you know, meeting the expectation but then not
coming to a positive resolution. There is one other piece that
we haven't talked about, if I could just introduce that, which
is the Rare Disease Innovation Hub. If we want to talk about
things that Congress could proactively do.
We have a tool that is modeled after what was very
successful in oncology, the Center of Excellence, but my
observation would be is it is underfunded and probably under
empowered to do what it needs to do.
When we think about advisory committees, when talk about
staffing at the FDA, when we think consistency between
reviewers, Congress could directly fund the Rare Disease
Innovation Hub in a meaningful way that would allow us to train
rare disease experts that could sit across review teams, across
review divisions, and bring some of that consistency, that
humanity, that humility, but that expertise that perhaps each
of the individual teams or the new reviewer on the team doesn't
quite have.
Again, I think we have a lot of the tools that we need. We
just need to encourage the FDA to use them in the right way and
that is one example we haven't talked about here today where
Congress could fund that directly and allow the FDA to make it
a much more valuable tool for rare disease drug development.
Senator Gillibrand. Thank you, Mr. Chairman.
The Chairman. You know, when you hear the testimony, I
think all of us internalize it. I have got six grandsons and a
granddaughter and you know, thank God they don't--you know,
everybody has got problems, right, but you know, they don't
have a rare disease that is going to shorten their life.
I can't imagine what a family is going through when they
have a family member that has something and then they believe
there is a possibility that something could change their life,
and it doesn't happen. I mean, I would be pretty frustrated. I
would be pretty--more than that. Ms. Kennedy, is it important
for people to come to Congress and talk about their concerns
with regard to the drug approval process?
Ms. Kennedy. Well, I know you are asking me, but there are
about 800 people on the Hill that would be happy to answer that
question as well.
Throughout this time here this morning, starting with your
opening remarks, we have cited many laws that have been
transformational for our rare disease community, and every
single one of them started with a member of the community
meeting with their elected official and talking about a
roadblock that could be transformed and turn into a resource
and a tool.
Every single one of those laws has transformed lives and
ultimately has saved lives. So the answer to your question is
an emphatic yes, and we are so grateful for the time you take
to be with our community, to listen to our community, to
engage, and to become partners with all of us, so thank you.
The Chairman. Does the FDA appreciate when you guys come
here?
Ms. Kennedy. I think many do, yes. Maybe some no, but I
think overall, over the years, I have been in this space 30
years and I think we have had strong partnerships with the
agency and many times the agency has very much appreciated our
support.
The Chairman. Dr. Schmahmann, what--from a clinical
standpoint, what happens to patients with progressive
neurologic diseases when access to treatment is delayed due to
the regulatory process rather than safety concerns?
Dr. Schmahmann. They progressively deteriorate. They lose
function. They can't live their lives, go to work, spend time
with their family, make a living, be productive citizens of
society in that way. They become part of the family that people
have to take care of instead of taking care of the families
themselves. Then they become progressively debilitated and then
they die young.
Then family members, in our case, see that. They see their
future in the mirror. There is a high incidence of depression
and, in fact, suicidality in this patient community as well.
This is across the spectrum. This is not a motor control
problem alone. This is a social, emotional, societal issue and
the issue about medications that improve neurological function
in real time work at the level of the physiology where brain
cells are sick before they die.
If you have a medication, even though it is not a gene
therapy, you have medication like troriluzole, where we know
the mechanism, and you stop the neurons from being so
hyperactive that they die, you actually improve function and
you slow disease over time, so you are modifying the disease.
The absence of a medication that can treat the disease
means that each day that this drug, troriluzole, and others
like it are not being approved means patients are losing brain
cells and are closer to death. It is heartbreaking to see, as
you all said at the outset, and we are hoping that this can
change from today.
The Chairman. I think in your testimony you said that the
FDA suggested withdrawing patients from compassionate use of
care to evaluate whether their conditions would deteriorate
despite physicians expressing the harm would be irreversible.
So tell me about the--what are the ethical implications of
that?
Dr. Schmahmann. If you have a disease where there is a
symptom like a migraine, for example, you can see if I stop the
drug, will you get worse for a week or two, or a month, and I
will put you back on drug, you are okay. In a neurodegenerative
disease like these, and I am going to be--excuse me if I am
provocative--the last time we had a catastrophe in medical
science in the U.S. was between 1922 and 1972.
I believe there was like a 40-year period, 1932 to 1972,
when people with syphilis were not treated so that the doctors
could see what happened to them, and the patients were not
told. That is a case study for every person who is going into
human studies research in the United States.
We learn about that case. You cannot treat patients like
guinea pigs. You have to have them on your story as part of the
research collaborator, experts by experience. If we have a
drug, as we do here, that is first safe and that bends the arc
of the disease, and you want patients to come off that drug so
you can see if they worsen, in other words if their brain cells
are dying under your care, that is a poster child--it is
Tuskegee version two, and it is entirely unacceptable. I reject
it outright.
They should not have recommended that and whoever did, I
would suggest they take updated education sessions on clinical
trials and on human studies research. It is not okay, Senator.
The Chairman. I can't imagine doing that. Mr. Campbell,
talk about inconsistent FDA standards, how it impacts
timelines, costs, the ability of small biotech companies to
survive. Is it easier to raise money if the FDA is
inconsistent? Does that make your job easier?
Mr. Campbell. No, is the candid answer, and you know, that
is underlying all of this, right. We have created in the United
States this rich ecosystem of innovation, which has been
supported by Congress, supported by FDA over the years,
supported by modern technology, and that brings in new
companies that bring in new innovations and offer some of the
therapies that we have talked about here today that are now
stuck in front of this regulatory process.
The reality is, and this is in my written testimony, the
reality is for many small and mid-sized biotech companies, it
takes decades to become profitable, which means we are going
hand-in-mouth begging for dollars from investors. If there is a
clear path forward and investors can be confident of an
eventual return, then they will keep investing and the
innovation ecosystem keeps going and going.
If we continue to create this uncertainty, if we continue
to create an uncertainty around manufacturing timelines, around
approval timelines, around changing the goalposts again, I am
confident that those investor dollars will go somewhere else.
I will tell you transparently, having gone to the recent
J.P. Morgan Healthcare Conference, which I am sure folks know
is the big investor conference in our industry, I heard more
opportunities about Chinese therapeutics and companies than
ever before, and I don't think that is an accident.
Ten, twenty years ago, we might have thought the science
wasn't good. We might have distrusted the quality and the
safety. I can tell you that the innovation there and the
science is equally as good as ours.
We still have an advantage, but if we are not careful, we
are going to lose that advantage, and at the end of the day,
the American patients suffer, the American economy suffers, and
I am convinced that that is a real threat, in addition to the
most important piece, which is making sure drugs get to
patients faster.
The Chairman. Dr. O'Neill, in progressive rare diseases,
how should regulators account for the fact that clinical
decline is often irreversible? Should the harm of waiting be
weighed alongside uncertainty in the data? If so, how?
Dr. O'Neill. Thank you. Yes, to call back to Dr.
Schmahmann's points around this and about exposure to not being
on drug, the risks of not treating this disease are known. You
know, these are not in question.
We know these children will be permanently, severely brain
injured for the rest of their lives. There are critical, time-
sensitive neurodevelopmental windows in childhood when it is
important to intervene to be able to receive the maximum
benefit. There is a continuum of this, but earlier is always
better.
What we are still hearing as recommended to sponsors is
that observational, or no treatment, or placebo controlled
trials are being recommended for these pediatric conditions.
This is very, very troubling when we know that they will become
brain injured. We have also seen--you know, when parents ask me
about this, I have to kind of step back and think, oh my
goodness, I know what a perfect science experiment looks like.
Yes, that is the perfect science experience, but these are
children. You cannot do good medicine unless you are putting
the patients first and following the ethics of medicine and we
have heard changes around the use of animals in preclinical
studies. Just last April, the FDA published its roadmap to
reducing animal testing in pre-clinic studies, and this says, I
quote, "due to the limitations of animal testing as well as
ethical concerns about animal testing, there have been
increased focus within the scientific community on new approach
methodologies."
We are concerned about the ethics of animal testing more
than we are concerned about the ethics of allowing children to
be brain injured in clinical trials, and I think we all need a
gut check on that.
The Chairman. Would any of you like to talk about what
patients and caregivers tell you about their willingness to
accept uncertainty or incomplete data when the alternative is
no treatment at all?
Dr. Schmahmann. I think it starts off with safety. Nobody
likes side effects, and patients do want to know that the
medications are safe, or the approaches are safe. Given that
piece, if we can make a comment about safety, the degree to
which the medication works or not is often something that
patients, I think, are willing to take on.
We can certainly hear from the others about that and the
other rare diseases. In our space, knowing that the medications
we have available are safe, and have been shown in other
circumstances, patients are not just willing, they are--we are
getting emails every day from people around the world, what
trials do you have for me that I can use to try and slow down
the process of my disease?
Ms. Kennedy. Yes. I really appreciate that question, and I
think my response would be that for each subpopulation within
each condition, within each targeted therapy, that
consideration would be very different, which is why Congress
authorized the use of the benefit-risk framework within the
consideration of regulatory review. That is one of the things
that we are concerned about is not being applied.
We don't know how it is being used. One of the things that
we are asking for today is more questioning around how are
these tools being utilized, because every community for every
clinical trial within every subpopulation of that community
will approach that threshold for risk tolerance differently.
That is a super important question, Senator, and we are
just not sure that that is being questioned the way it was
intended for the tailorization that is required for rare
disease therapeutic development.
The Chairman. Mr. Campbell, can I ask you a separate
question? How important is transparency from the FDA in
maintaining trust with rare disease communities? What happens
when explanations for delay are unclear or incomplete?
Mr. Campbell. You know, I feel like as sponsors,
manufacturers, we have a great duty to our patients. I think
somebody--one of the Senators asked me why I am in this
business. I will tell you, you know, it is for the patients,
but when you have a chance to develop a therapy for people
living with a rare disease, it sort of gets in your blood. You
also, then you bear a great responsibility.
I feel, I think, like sponsors are at the front lines, in
front of the agency trying our best to get those drugs over the
finish line. If we fail to do that for any reason, we owe it to
the patients, to the community, to the caregivers to give them
an explanation. When there is no good explanation or when the
explanation is a crack on the floor, you know, that is just not
good enough.
I think I really do believe that sponsors bear some of that
responsibility. I think it works best when we truly work
together. Congress has the tools. The FDA has proven itself
over time to be very effective in working with sponsors. I
shared our story, which was an incredible, innovative
regulatory science, medical science that helped thousands of
patients.
If you don't have that transparency, and if you do not have
that consistency then, you know, we all lose, and I really
believe that we are at the center of that. It pains me, you
know, to hear these stories.
We are not in that position today as Amicus, but we owe a
responsibility to these people who are giving their lives to
participate in clinical studies who have so much hope, we owe
them clarity and we all do. Everybody who is involved in that,
including the regulators.
The Chairman. Ranking Member Gillibrand, you want to say
anything before we close?
Senator Gillibrand. I would like the audience members who
have pictures of their loved ones to stand please so we can see
their loved one. Thank you for coming to represent them. Thank
you all. I want to just thank our guest who is in the corner
who has been so well behaved this entire time. I am very proud
of her for being such a good girl. Just thank you all for being
here today. This has been an extremely powerful hearing. We
have gotten some amazing testimony, and I am very hopeful that
we will find better solutions so that we can all work together
to get these cures that our loved ones so desperately need.
Thank you all.
The Chairman. I want to thank everybody for being here. I
want to thank the Ranking Member for this. We have been doing
this for a little over a year, and we have been able to do a
lot of things together.
What we heard today was not abstract policy theory. We
heard from Mr. Campbell that 95 percent of rare diseases still
have no approved treatment. At the current pace, it could take
more than a century to meaningful close that gap. We heard Dr.
Schmahmann about a multi-year data set supported by real-world
evidence and natural history comparisons, showing meaningful
showing of disease progression, yet still unable to clear the
regulatory bar.
We heard from Ms. Kennedy that at least 23 rare disease
therapies received complete response letters in the past year,
even as advisory committee meetings declined, raising concern
about whether the flexibility Congress authorized is being
applied consistently. We are reminded that for some patients,
success is not an abstract endpoint, but the ability holds one
breath long enough to survive another moment.
I recently spoke with Commissioner Makary. It was clear
that the FDA's framework was built for common diseases, not
rare to ones. He is implementing reforms like the plausible
mechanism pathway, greater flexibility for gene therapies, and
strengthening the rare disease innovation hub. We look forward
to working with him to ensure those changes are applied
consistently and urgently for patients. He inherited a broken
system, and the FDA cannot be fixed overnight.
That said, he has made significant progress, and I am
completely encouraged by the reforms President Trump has
empowered Commissioner Makary to make at the FDA, and I know he
cares deeply about getting results and making sure the United
States remains the world's leader for innovation and treatment
of rare diseases.
Taking together the testimony presented before our
Committee today makes one thing clear, the question is not
whether to protect safety, it is whether the system is moving
with the urgency Congress intended and patients require. The
Committee will continue exercising oversight to ensure that
flexibility enacted into law becomes reality in practice.
I look forward to continuing work with our members. If any
Senator has additional questions for the witnesses or
statements to be added, the hearing record will be open until
next Wednesday at 5:00 p.m. Thanks everybody for being here.
[Whereupon, at 11:05 a.m., the hearing was adjourned.]
=======================================================================
APPENDIX
=======================================================================
Prepared Witness Statements
=======================================================================
[GRAPHIC NOT AVAILABLE IN TIFF FORMAT]
=======================================================================
Questions for the Record
=======================================================================
U.S. Senate Special Committee on Aging
"From Regulator to Roadblock: How FDA Bureaucracy Stifles Innovation"
February 26, 2026
Questions for the Record
Annie Kennedy
Senator Raphael Warnock
Question:
Over the past few decades, the FDA has adopted strategies
to accelerate the development of treatments for ultra-rare
diseases. These strategies have included the Support for
Clinical Trials Advancing Rare Disease Therapeutics Pilot
Program, Rare Disease Evidence Principles, and the Plausible
Mechanism of Action Framework. However, there are many rare
diseases that still need treatments.
What would be the advantages of the FDA extending the above
strategies to other rare diseases? How can Congress ensure the
FDA balances acceleration and thoroughness in its review of
potential rare disease treatments?
Response:
We have been following closely the recent agency
announcements, including the Rare Disease Evidence Principals
(RDEP) initiative, the Plausible Mechanism Framework, the
establishment of the Rare Disease Innovation Hub in 2024, and
the implementation of new guidance documents and regulatory
science pilot initiatives contained in PDUFA VII (10/1/2022 -
9/30/2027).
The application of these programs and policies can shape
the prospects of rare disease therapy development for a given
community, drive investment into one area and out of another,
and determine how patient advocacy organizations allocate
precious resources. For a variety of reasons the ways in which
available guidances, programs, and pathways can be applied to
different subpopulations of rare diseases differ. Multiple
factors have led to some rare disease communities having
greater success in leveraging FDA's regulatory flexibility
including population size, therapeutic modality, disease
characterization, extent of diagnostic delays, age of onset,
and others.
We are encouraged by the intent signaled by FDA's most
recent initiatives, RDEP and the Plausible Mechanism Framework,
however, more information is needed to understand how the
Agency plans to operationalize these new approaches for
products in today's pipeline and beyond, and which
subpopulations of rare diseases stand to benefit initially, and
over the longer term.
We encourage additional dialogue and input from the
community into these new initiatives as even the best ideas
need the benefit of robust dialogue and operational details for
them to have the intended effect.
Specific to the RDEP announcement - this announcement
appears to be responsive to calls for more predictability in
the regulatory process, but more details will be needed before
we have a detailed reaction. Many rare disease communities may
not realize the program's benefits due to its narrow focus;
however, it can provide valuable insights for expansion if
appropriate metrics and evaluation methods are incorporated
from the outset.
We are eager to hear more details on how RDEP will be
operationalized, as well as a better understanding of how
RDEP's requirements for pre-specifying the trial requirements
will be handled, given the nature of many rare disease trial
designs.
Regarding the Plausible Mechanism Framework, we are
encouraged by the release of the draft Guidance, and what it
represents for the eligible communities for whom traditional
approaches to clinical trials and regulatory requirements are
fundamentally at odds with the reality of their conditions. We
are grateful to the FDA for taking on this challenge of
ensuring no disease is too rare to deserve treatment. And we
are incredible grateful to the many families and experts who
applied their personal expertise to yield transformational
change.
We also recognize that for many in our rare disease
community, the Plausible Mechanism Framework will not apply,
and we urge FDA leadership to continue pursuing solutions that
will ensure the tools and policies that Congress has created
over decades, are deployed in a predictable and consistent
manner that can unleash scientific innovation and speed safe
and effective therapies to patients across the more than 10,000
rare diseases. The EveryLife Foundation team is in the process
of closely reviewing the recently released draft Guidance.
Regarding the Rare Disease Innovation Hub and opportunities
yielding from PDUFA VII Pilot Programs, we are hopeful that the
opportunities stemming from these PDUFA VII investments will be
applied more broadly across rare disease product development.
The Rare Disease Innovation Hub is well positioned to be a
catalyst of progress by spearheading the dissemination of data,
case studies, and other learnings resulting from these pilots
and experiences with the application of regulatory flexibility
tools more broadly.
Since 1983, Congress has created incentives and policies
that recognize the inherent complexities in developing
treatments for rare diseases. Congress has explicitly given the
FDA authority to uphold the highest standards of regulatory
safety and rigor, while applying tailored approaches (i.e.
"regulatory flexibility"). Such approaches include:
Establishment of the accelerated approval pathway
Consideration of the totality of evidence in the
regulatory review
Inclusion of Patient Experience Data (PED) in clinical
trial design & regulatory processes
Utilization of innovative clinical trial designs and
real-world evidence (RWE)
Nearly 1,400 orphan-designated therapies are changing the
lives of patients and families, but 95% of rare diseases remain
without an FDA-approved treatment.
Congress must continually ensure that FDA review statutes
keep pace with the science and are designed to work across the
spectrum of rare diseases, from n-1 to just under 200,000, and
from pediatric to adult populations. Congress should look to
address gaps more regularly, ideally more often than the
typical practice of moving regulatory legislation alongside the
five-year PDUFA reauthorization window allows. Congress should
regularly engage in dialogue with the Agency leadership and
rare disease stakeholders, seek comprehensive metrics to
understand how the Agency is applying regulatory flexibility,
and ensure the Agency has adequate resources, such as funding
for the Rare Disease Innovation Hub, to optimize their ability
to apply tailored approaches to rare disease product
evaluation.
Question:
As part of his sweeping reductions-in-force (RIFs) of
Department of Health and Human Services (HHS) employees, HHS
Secretary Robert F. Kennedy dismissed 3,500 Federal Drug
Administration (FDA) employees in April 2025. The RIFs targeted
employees across the agency, including advisory committee
staff.
You mentioned that the FDA held far fewer advisory
committee meetings in 2025 relative to 2024 and that this
drastic drop meant fewer opportunities for experts and patients
to share information to inform the FDA's decision-making. What
are the ramifications of last year's RIFs at the FDA for the
development and treatment of illnesses that do not yet have a
cure?
Response:
Significant leaders the rare disease community has built
relationships with over the years have either resigned or been
laid off in the last 12 months, resulting in the loss of
powerful allies and institutional knowledge that have generated
the progress the rare disease community has seen over the last
decade. However, thousands of committed public servants remain,
and the EveryLife Foundation, together with our community, is
committed to policies that will support and enhance the
Agency's rare disease capacity and expertise.
Rare disease product reviews occur in every division and
product Center at the FDA. With the appropriate resources, the
Rare Disease Innovation Hub is poised to enhance its role as
the FDA's coordinating office to optimize rare disease
expertise, processes, and engagement with stakeholders across
all therapeutic areas, including drugs, cell and gene
therapies, and medical devices. Given the departure of
experienced staff, the importance of a robust Rare Disease
Innovation Hub is magnified. The Hub's first full year of
operations has laid the foundation for meeting this moment of
opportunity if institutional support and resources are
enhanced.
Question:
How can Congress conduct oversight over the FDA to ensure
the agency continues to hold advisory committee meetings and
review rare disease treatments?
Response:
We are concerned about the dramatic decline in
opportunities to leverage external scientific, clinical, and
patient-community insights to inform deliberations on complex
rare-disease product reviews. While not every product
application requires an advisory committee, where relevant,
their use was one of the few ways the Agency discussed its
approach to the review in public and heard from clinicians who
treat patients and run trials, and from the patients and
families who took part. This additional insight affords review
teams with another data point to consider among the totality of
evidence they must balance when determining how to apply the
regulatory flexibility tools that Congress has authorized.
As I encouraged Congress in my testimony, Congress should
conduct outreach to the Agency to understand its approach to
the following:
The application of the accelerated approval pathway to
rare disease therapies;
Improving the predictability and consistency of the
application of regulatory flexibility; and
Resuming the use of Advisory Committee Meetings to
receive external expertise on product reviews and key policy
topics.
Based on this engagement and the Agency's responses, we
encourage Congress to identify opportunities for additional
public dialogue with the Agency and rare disease stakeholders
to identify a path forward that will ensure sustainable,
transparent, and predictable processes for leveraging external
expertise in relevant product reviews and to inform overall
rare disease regulatory science approaches moving forward.
U.S. Senate Special Committee on Aging
"From Regulator to Roadblock: How FDA Bureaucracy Stifles Innovation"
February 26, 2026
Questions for the Record
Bradley Campbell
Senator Raphael Warnock
Question:
Approximately one in ten Georgians live with a rare
disease. Many of these individuals, including older adults, do
not have access to life-saving treatments due to incomplete
scientific knowledge of their disease and limited funding.
Families seeking treatments that were reviewed under a priority
voucher program are also experiencing delays due to the
prolonged FDA approval process.
How can Congress reduce regulatory barriers to expedite the
FDA's approval process for rare disease treatments while
maintaining the safety and quality of these treatments?
Response:
Senator Warnock, thank you for this thoughtful question. As
noted in my testimony, I believe there are low-hanging fruit
that we can seize while still maintaining FDA's "gold standard"
for safety and efficacy:
Speeding up approval of early phase clinical trials
Harnessing innovative endpoints based on biomarkers
Expanding the use of real-world evidence
Streamlining manufacturing inspections
In cases where there is residual uncertainty about the
durability or extent of patient benefit for promising
therapies, real-world data should be collected post-approval
via the Accelerated Approval pathway.\1\ If that data does not
bear out patient benefit, the agency should consider
withdrawing that treatment in consultation with the patient
community. When it comes to rare diseases, patients and their
families are the true experts, and their voices need to be
respected as such.
---------------------------------------------------------------------------
\1\ Examples of rare-disease therapies that entered the market via
FDA Accelerated Approval and later converted to full approval include
sparsentan for primary IgA nephropathy, agalsidase beta for Fabry
disease, and delandistrogene moxeparvovec-rokl for Duchenne muscular
dystrophy.
---------------------------------------------------------------------------
FDA already has Congressionally granted authority to do
everything I listed above. The challenge is simply doing them
consistently. This is where Congressional oversight is vital.
Question:
How do bipartisan initiatives like the FDA Pediatric
Priority Review Voucher program, which I was glad to see
reauthorized recently, help incentivize innovation for rare
disease treatments?
Response:
Senator Warnock, we are deeply grateful to Congress for
reauthorizing the FDA's Pediatric Priority Review Voucher (PRV)
program.
Small and mid-size biotech companies are the driving force
behind U.S. drug development for all diseases, but particularly
for rare diseases. These companies are often pre-commercial,
meaning they are years-to-decades from sustainable
profitability.
When a company with a PRV voucher receives FDA approval,
the sponsor can sell that voucher, sometimes for hundreds of
millions of dollars. That funding is a critical lifeline for
continued operations when the alternative is bankruptcy.
Rare pediatric diseases that have benefited from PRVs
include pediatric neuroblastoma, the most common cancer in
infants; spinal muscular atrophy (SMA), the most common genetic
cause of infant mortality; and epidermolysis bullosa, which
causes fragile, blistering skin.
There we no treatments for any of these diseases before
Congress created the PRV program in 2012.
The PRV program has no cost to taxpayers, but when
investors are considering whether to fund an early-stage rare
disease company, having a PRV designation can be decisive.
=======================================================================
Statements for the Record
=======================================================================
[GRAPHICS NOT AVAILABLE IN TIFF FORMAT]
[all]