[Senate Hearing 118-177]
[From the U.S. Government Publishing Office]


                                                        S. Hrg. 118-177

                       UNLOCKING HOPE: ACCESS TO
                    THERAPIES FOR PEOPLE WITH RARE,
                   PROGRESSIVE, AND SERIOUS DISEASES

=======================================================================

                                HEARING

                               BEFORE THE

                       SPECIAL COMMITTEE ON AGING

                          UNITED STATES SENATE

                    ONE HUNDRED EIGHTEENTH CONGRESS


                             FIRST SESSION
                               __________

                             WASHINGTON, DC
                               __________

                            OCTOBER 26, 2023
                               __________

                           Serial No. 118-09

         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
                    
54-248 PDF                 WASHINGTON : 2024           


                       SPECIAL COMMITTEE ON AGING

              ROBERT P. CASEY, JR., Pennsylvania, Chairman

KIRSTEN E. GILLIBRAND, New York      MIKE BRAUN, Indiana
RICHARD BLUMENTHAL, Connecticut      TIM SCOTT, South Carolina
ELIZABETH WARREN, Massachusetts      MARCO RUBIO, Florida
MARK KELLY, Arizona                  RICK SCOTT, Florida
RAPHAEL WARNOCK, Georgia             J.D. VANCE, Ohio
JOHN FETTERMAN, Pennsylvania         PETE RICKETTS, Nebraska
                              ----------                              
               Elizabeth Letter, Majority Staff Director
                Matthew Sommer, Minority Staff Director

                         C  O  N  T  E  N  T  S

                              ----------                              

                                                                   Page

Opening Statement of Senator Robert P. Casey, Jr., Chairman......     1
Opening Statement of Senator Mike Braun, Ranking Member..........     1

                           PANEL OF WITNESSES

Brian Wallach, JD, Co-Founder, I AM ALS, Kenilworth, Illinois 
  (Accompanied by Wife, Sandra Abrevaya).........................     6
Maureen Bell, Galactosemia Patient and Advocate, Chalfont, 
  Pennsylvania...................................................     8
Margaret Plews-Ogan, MD, Brodie Professor of Medicine, University 
  of Virginia, Charlottesville, Virginia.........................    10
Anish Bhatnagar, MD, Chief Executive Officer, Soleno 
  Therapeutics, Redwood City, California.........................    12
Holly Fernandez Lynch, JD, MBE, Assistant Professor of Medical 
  Ethics and Law, University of Pennsylvania, Philadelphia, 
  Pennsylvania...................................................    13
Keith Desserich, Chairman/Co-Founder, The Cure Starts Now 
  Foundation, President, Pediatric Brain Tumor Consortium 
  Foundation, Cincinnati, Ohio...................................    15

                                APPENDIX
                      Prepared Witness Statements

Brian Wallach, JD, Co-Founder, I AM ALS, Kenilworth, Illinois....    37
Maureen Bell, Galactosemia Patient and Advocate, Chalfont, 
  Pennsylvania...................................................    42
Margaret Plews-Ogan, MD, Brodie Professor of Medicine, University 
  of Virginia, Charlottesville, Virginia.........................    44
Anish Bhatnagar, MD, Chief Executive Officer, Soleno 
  Therapeutics, Redwood City, California.........................    47
Holly Fernandez Lynch, JD, MBE, Assistant Professor of Medical 
  Ethics and Law, University of Pennsylvania, Philadelphia, 
  Pennsylvania...................................................    49
Keith Desserich, Chairman/Co-Founder, The Cure Starts Now 
  Foundation, President, Pediatric Brain Tumor Consortium 
  Foundation, Cincinnati, Ohio...................................    71

                        Questions for the Record

Brian Wallach, JD, Co-Founder, I AM ALS, Kenilworth, Illinois....    77
Margaret Plews-Ogan, MD, Brodie Professor of Medicine, University 
  of Virginia, Charlottesville, Virginia.........................    79
Anish Bhatnagar, MD, Chief Executive Officer, Soleno 
  Therapeutics, Redwood City, California.........................    84
Holly Fernandez Lynch, JD, MBE, Assistant Professor of Medical 
  Ethics and Law, University of Pennsylvania, Philadelphia, 
  Pennsylvania...................................................    87
Keith Desserich, Chairman/Co-Founder, The Cure Starts Now 
  Foundation, President, Pediatric Brain Tumor Consortium 
  Foundation, Cincinnati, Ohio...................................   116

                       Statements for the Record

Statement of Lisa Murkowski......................................   121
Statement of I AM ALS............................................   122
Patients' Statements for the Record..............................   125

 
                       UNLOCKING HOPE: ACCESS TO
                    THERAPIES FOR PEOPLE WITH RARE,
                   PROGRESSIVE, AND SERIOUS DISEASES

                              ----------                              
                       Thursday, October 26, 2023




                                        U.S. Senate
                                 Special Committee on Aging
                                                    Washington, DC.
    The Committee met, pursuant to notice, at 10:03 a.m., Room 
106, Dirksen Senate Office Building, Hon. Robert P. Casey, Jr., 
Chairman of the Committee, presiding.
    Present: Senator Casey, Gillibrand, Blumenthal, Warren, 
Warnock, Braun, Rick Scott, Vance, and Ricketts.

                 OPENING STATEMENT OF SENATOR 
                 ROBERT P. CASEY, JR., CHAIRMAN

    The Chairman. Good morning. The Senate Special Committee on 
Aging will come to order. Welcome, everybody. Welcome to the 
Committee's eighth hearing of the 118th Congress about drug 
development for rare and serious diseases.
    As is the tradition of the Committee, the Aging Committee 
Ranking Member, Ranking Member Braun on this case, will offer 
an opening statement.

                 OPENING STATEMENT OF SENATOR 
                   MIKE BRAUN, RANKING MEMBER

    Senator Braun. Thank you, Senator. I thank the witnesses 
for coming and for all the folks from around the country here 
today.
    There are over 7,000 rare, progressive, and serious 
diseases known to man. It is estimated that 95 percent lack 
treatment. Yet in my time as Senator, there has not been one 
Senate hearing to examine promising therapies for people with 
rare, progressive, and serious diseases.
    The room is packed with people, patients, and caregivers 
that live this reality every single day. Right here, 350 
patient stories from 44 states. This is long overdue. People 
that watch their bodies deteriorate in real time. Family 
members who have seen their loved one go from the picture of 
health to knocking on death's door.
    Parents that buried their children before they even started 
school. I want to recognize and thank each one of you that are 
here in the audience and let you know I think this is the 
beginning of a new day for what we are all interested in.
    Chairman Casey, in response to this hearing, our Committee 
has received these letters, 350 of them, 44 states, with 
personal experi

[[Page 2]]

ences. I ask by unanimous consent that we enter these into the 
record.
    The Chairman. Without objection.
    Senator Braun. Thank you. A wide variety of disease groups 
are represented in these submissions, including ALS, DIPG, an 
extremely aggressive pediatric cancer, and Barth syndrome, an 
ultra-rare genetic disorder that regularly results in death 
from heart failure before a child's fifth birthday.
    Importantly, none of the diseases that our constituents 
have contacted us about have any form, have any form of FDA 
approval treatment. Not one of them. These diseases are 
relentless.
    They are widespread and devastating. Most are considered a 
death sentence, but they are not invincible, and our 
constituents are not helpless. Patients deserve a promising 
pathway at the FDA.
    Today, I am joined by Senators Gillibrand, Wicker, Cramer, 
Murkowski, Manchin, and Warnock in sponsoring the Promising 
Pathway Act to create a more flexible, accessible, and 
compassionate drug approval system at the FDA, and if there is 
any indication from the hour and a half I spent on the Senate 
floor yesterday, we are going to be getting a lot more Senators 
on this Bill. The Promising Pathway Act would create a rolling, 
real time drug approval pathway to speed access for individuals 
with these rare diseases.
    This Bill does not undermine patient safety or FDA's gold 
standard for drug approvals in any way. Therapies developed 
through the pathway will be rigorously evaluated and 
continuously studied using real world data.
    I ask unanimous consent to enter into the record a letter 
of support for this hearing signed by 15 individuals and 
organizations.
    The Chairman. Without objection.
    Senator Braun. The Promising Pathway Act is a commonsense 
step to give the FDA the flexibility it needs to serve 
Americans with these most trying diseases.
    Our constituents continue to fight for new treatments, 
greater access, and full lives. I ask my colleagues to join me 
in unlocking hope for these constituents. I yield back to you, 
Senator Casey.
    The Chairman. I want to thank Ranking Member Braun. Of 
course, he worked to put this hearing together, and his staff 
and our staff, and I am grateful for your work on this. This is 
a topic that is obviously meaningful to everyone in this room 
and every member of the Committee, and we look forward to a 
robust discussion about this topic today.
    As Ranking Member Braun outlined, rare diseases are those 
that affect some 200,000 Americans, and over 7,000 rare 
diseases have been identified, 7,000. While each individual 
rare disease may affect only a small number of people.
    Collectively, it is estimated that some 25 to 30 million 
Americans are living with a rare disease. We have done a lot of 
research into and drug development for these rare diseases. In 
1983, prior to the passage of the Orphan Drug Act, there were 
just 38 drugs approved to treat rare diseases.
    In the 40 years since, we have over 1,100, 1,100 new drugs 
or new indications for drugs approved for rare diseases. I am 
proud to have worked on legislation entitled the Creating Hope 
Act to

[[Page 3]]

incentivize the development of drugs for rare pediatric 
diseases, in particular, and other legislation to address some 
of the challenges faced by those living with what you might 
call ultra-rare diseases, which affect even a smaller number of 
people.
    My legislation, the Creating Hope Act, captures what we as 
legislators are trying to do, to give Americans living with 
rare diseases hope for the future, and while we have made some 
progress, many challenges remain as we will hear from our 
witnesses today. To many people living with and dying from rare 
diseases still do not have FDA approved therapies to treat or 
mitigate their conditions.
    I believe that every one of these individuals deserves 
access to an FDA approved safe and effective therapy, so we 
must make sure that research continues and that clinical trials 
are designed to allow effective therapies to reach patients as 
quickly as possible.
    Rare diseases and the research and clinical trials for 
drugs to treat them are fundamentally different from more 
common conditions. We will explore some of those differences 
today and the ways in which they present challenges for drug 
development through our witnesses and their testimony today.
    It is important to note that my observations on the 
challenges facing the rare disease community and the steps we 
might consider to address these challenges don't necessarily 
apply to other non-rare conditions, but as we will hear today, 
the challenges for drug development start from the earliest 
stages of development.
    When patient populations are small, it is hard for 
clinicians and researchers to develop what is known as a 
``natural history'' for the disease and what the trajectory of 
the disease is when it is not treated.
    Natural histories are important for developing therapies 
because if you don't understand how a disease progresses, it is 
hard to measure whether a new therapy is working. Rare diseases 
often are heterogenous, meaning that not every patient disease 
will progress in the same way, compounding the problem of 
poorly understood natural histories.
    Once a promising drug candidate makes it to clinical 
trials, there are further challenges. Drugs intended to treat 
common conditions are tested in hundreds of thousands of 
people. When your entire patient population is only a few 
thousand or a few hundred, or a few dozen, it is simply not 
possible to do the same type of clinical trials.
    When you have smaller trials, it is more difficult to 
demonstrate efficacy. In recent years, the FDA has taken action 
to improve how it works with companies developing drugs for 
rare and serious conditions, and the agency has done a lot more 
work to hear directly from patients affected.
    More recently, the FDA has announced new initiatives 
specifically aimed at supporting drug development for rare 
diseases, such as the Support for Clinical Trials, Advancing 
Rare Diseases Therapeutics, or START, the acronym START, S-T-A-
R-T. This is a pilot program to enable real time communication 
between a drug sponsor and the FDA staff on these development 
issues.
    Another important initiative of the FDA is the Rare Disease 
Endpoint Advancement Pilot Program to support drug sponsors' 
ability

[[Page 4]]

to engage with the FDA around the development of so-called end 
points, the metrics of efficacy for drugs for rare diseases.
    In the last decade, the FDA has also done more to hear 
directly from patients with patient focused drug development. 
These are meetings that give the FDA staff the opportunity to 
hear directly from patients about how their disease affects 
them and what drug effects are meaningful to them in their 
daily lives.
    I support the agency's recent steps, but we should continue 
supporting and strengthening their authorities and to do more 
to facilitate more approvals of safe and effective drugs. I 
look forward to hearing today's recommendations from our 
witnesses about the steps we can take to lead to more FDA 
approved treatments for rare diseases.
    Next, we will move to our witness introductions. I am 
pleased to turn to our first witness. Our first two witnesses, 
I should say, will be sharing their experiences as patients and 
advocates, but in this case, they will not be answering 
questions. They will be providing opening remarks virtually, 
and for our first virtual witness, I am glad to turn to Ranking 
Member Braun.
    Senator Braun. Thank you, Mr. Chairman. My pleasure to 
introduce Brian Wallach. From the time that Chris Coons and I 
formed the ALS Caucus here in the Senate, which has been an 
active one, we have gotten to know Brian well over that time. 
Really needs no introduction.
    He is a true changemaker and champion. Brian has a storied 
career as a regional campaign director and White House counsel 
for President Obama. He later became a Federal prosecutor in 
Chicago. His life took a turn in November 2017 when he was 
diagnosed with ALS and given six months to live at the age of 
37.
    Rather than accepting the status quo, he decided to fight. 
Along with his wife, Sandra, Brian co-founded I AM ALS, a 
nonprofit dedicated to cure ALS. Brian is a father of two young 
girls. Thank you for being with us here today, Brian.
    The Chairman. Thank you, Ranking Member Braun. Now I will 
read an introduction from my colleague, Senator Durbin, the 
Senior Senator from Illinois.
    ``I am so pleased that the Senate Aging Committee will be 
hearing from my constituent, Brian Wallach, this morning and I 
want to thank the chairman for affording me the opportunity to 
share a few words about Brian.
    One of the truly wonderful things about being a United 
States Senator is that people--is the people you get to meet 
along the way. People like Brian and his wonderful wife Sandra. 
Six years ago on the day they should have been focused solely 
on bringing their newborn second daughter home for the first 
time, this young family was confronted with an unimaginable 
diagnosis.
    Brian had ALS, a disease for which there is no cure and 
which as of now is fatal 100 percent of the time. Brian and 
Sandra quickly turned their grief into action starting I AM ALS 
and galvanizing the ALS community around advocating for 
increased attention, research, and results for all ALS patients 
and their families, and boy, have they had success. Brian and 
Sandra have been the driving forces behind getting Act For ALS 
signed into law, ensuring Congress twice doubled the Department 
of Defense's ALS research

[[Page 5]]

budget, eliminating the five-month waiting period for ALS 
patients to get Social Security disability benefits, and 
working with the Food and Drug Administration to finally get 
several new ALS treatments on the market for the first time in 
years, and they are not done yet. I hope the Aging Committee is 
as inspired by Brian as I am, as I always am, and I look 
forward to hearing his recommendations for how we can continue 
to utilize the patient voice to make progress for ALS 
families.''
    That is a statement from Senator Dick Durbin. Our second 
witness, Maureen Bell is from Chalfont, Pennsylvania. Maureen 
was diagnosed with a classic gulacta--I am going to make sure I 
pronounce this right, galactosemia, seven days after her birth 
in 1972.
    Ms. Bell has experienced many of the challenges of those 
living with the disease have. She is an advocate for those 
living with this disease and a helpful resource for new 
patients with their newly diagnosed children.
    Thank you, Maureen, for sharing your experiences and your 
story with us. Now, I will turn to Ranking Member Braun for two 
witness introductions.
    Senator Braun. Thank you, Mr. Chairman. My pleasure to 
introduce Dr. Peggy Plews-Ogan. She is the Brodie Professor of 
Medicine at the University of Virginia Hospital. Peggy attended 
Harvard Medical School and completed residency at Brigham and 
Women's Hospital in Boston.
    In December of 2021, Peggy's husband, James, was diagnosed 
with ALS. She has since become a caregiver and an advocate with 
I AM ALS. Peggy and her husband have two children. Peggy, thank 
you for agreeing to testify, and James, thank you for being 
here today.
    Next witness, Dr. Anish Bhatnagar is the Chief Executive 
Officer of Soleno Therapeutics, which is a small biotech firm 
dedicated to treating rare genetic disorders. He has been with 
Soleno since 2006.
    He is a physician with over 20 years of experience in 
developing biologics, drug device combinations, and 
diagnostics, as well as therapeutic medical devices. Thank you 
for being here today, and I will turn to Senator Vance to 
introduce the next witness.
    Senator Vance. Thank you, Ranking Member Braun, and thanks 
to the Chairman for hosting this important discussion.
    As Senator for Ohio, I am proud to introduce a great Ohioan 
and a great Cincinnatian, Mr. Keith Desserich. Keith is the 
Chairman and Co-Founder of The Cure Starts Now Foundation, 
which is the leading international charity dedicated to finding 
cures for the rare pediatric brain cancers that may help cure 
other types of cancers.
    He is also the President of the Pediatric Brain Tumor 
Consortium Foundation. He and his wife, Brooke, established 
their foundation in 2007 after losing their daughter to a 
cancer called DIPG at the age of seven.
    Her public battle was memorialized in the best-selling book 
"Notes Left Behind," which was eventually translated into 22 
languages. Since then, the Cure Starts Now Foundation has 
invested more than $30 million in over 130 trials across 17 
countries.
    Keith helped create an innovative, organic, and linked 
registry that has become a model for other disease registries, 
and he is ad

[[Page 6]]

vocating today on behalf of public policy facilitating his 
important work rather than making it harder.
    Keith is also a steering committee member of the Pediatric 
Brain Tumor Consortium, the premier NIH funded brain cancer 
research initiative. Thanks, Keith, for being with us today.
    The Chairman. Thank you, Senator Vance. Now, I will 
introduce our sixth and final witness, Holly Fernandez Lynch. 
She is from Philadelphia, Pennsylvania. I should say, works in 
Philadelphia, but lives in Swarthmore, Delaware County, 
correct?
    Professor Fernandez Lynch is Assistant Professor of Medical 
Ethics in the Department of Medical Ethics and Health Policy at 
the Perelman School of Medicine at the University of 
Pennsylvania.
    A lawyer and bioethicist by training, Professor Fernandez 
Lynch's scholarly work focuses on the Food and Drug 
Administration pharmaceutical policy, access to investigational 
medicines outside of clinical trials, and clinical research 
ethics.
    Thank you, Professor, for sharing your expertise with us 
today, and so, we will start with our first witness, Brian 
Wallach, and Maureen Bell will follow him. Mr. Wallach, you may 
begin.

          STATEMENT OF BRIAN WALLACH, JD, CO-FOUNDER,

                 I AM ALS, KENILWORTH, ILLINOIS

    Mrs. Abrevaya. and Mr. Wallach. Chairman Casey and Ranking 
Member Braun, thank you for the opportunity to testify today. 
My name is Brian Wallach. I have been living with ALS for six 
years. ALS has changed every part of me.
    My legs no longer work, my arms no longer work. ALS has 
almost taken away my voice as well, which is why my amazing 
wife, Sandra Abrevaya, is reading this testimony. ALS is a 
disease that is 160 years old. Let me repeat that, for 160 
years, ALS has killed literally everyone diagnosed with it, 
everyone. That is simply unacceptable. Today, we hope to reform 
the FDA's approach to diseases like ALS.
    Under current FDA standards, it can take 15 years or more 
for effective drugs to move from pre-clinical work to approval. 
In the meantime, many people have rapidly progressive terminal 
conditions, including ALS, die and have no viable treatments or 
options or hope available to them.
    One of the lessons from the Neuron ADCOM is that there is 
in fact no such thing as a so-called gold standard across the 
FDA for how to approve new treatments for rare or fatal 
diseases. Instead, today's reality is that whether a treatment 
will be approved or not depends on what FDA center is in and on 
these specific individuals in the FDA review team assigned to a 
treatment.
    A second lesson is that the existence of the 2019 FDA 
guidance is simply not enough to ensure uniform approval 
standards of new treatments for ALS. We very, very 
unfortunately learned this lesson the hard way just a few weeks 
ago during the ADCOM for Neuron, when the question presented to 
the ADCOM did not incorporate the FDA's own 2019 guidance about 
regulatory flexibility.
    The primary question put before the ADCOM was, do the data 
presented demonstrate substantial evidence of effectiveness for 
treatment of mild to moderate ALS? This question did not at all 
make reference to the 2019 FDA guidance that stated, ``when mak

[[Page 7]]

ing regulatory decisions about drugs to treat ALS, FDA will 
consider, one, patient tolerance for risk. Two, the serious and 
life-threatening nature of the condition, and three, also 
within the context of statutory requirements for safety and 
efficacy.'' This is exactly why legislation, such as the 
Promising Pathways Act, is absolutely critical for people 
living with ALS. There is no FDA approved biomarker for 95 
percent of us living with ALS.
    What is the result of that? The result is that treatments 
for 95 percent of people living with ALS, including Brian, do 
not qualify for accelerated approval. The Promising Pathways 
Act addresses this issue by creating provisional approval.
    The Promising Pathways Act is also building the 
infrastructure to require drug sponsors to move faster in 
conducting their phase three trial and giving the FDA the 
authority to remove provisional approval if additional data 
makes clear that that is merited.
    We support efforts to bring safe, promising therapies to 
more people living with terminal diagnosis, pending full FDA 
approval. We also support efforts to increase spending on 
research into the causes of ALS and potential treatments, but 
we do not support saying to this generation, thank you for your 
contribution to research, now go home and prepare to die.
    While academics and bioethicists may have the luxury of 
debating theoretically what might look like some perfect 
system, us, people living with ALS today whose lives are 
literally on the line, we, we do not have that luxury and we 
are looking to you to provide them with the hope that they can 
live a little bit longer and maybe even be here to see a cure 
for ALS.
    The key here is that PPA approval is merely provisional. It 
affords early access to promising drugs to people with 
extremely serious conditions who are willing to take risks. It 
allows additional evidence about a drug's efficacy to be 
collected during the short two-year provisional approval 
windows.
    Provisional approval can occur only if a drug has been 
shown to be safe, and required patient registries enable much 
broader data collection about a drug's efficacy and safety than 
can even occur in traditional clinical trials. This data will 
help the FDA make even better decisions when it comes to the 
approval and labeling of new treatments.
    Moreover, drug sponsors presumably want to obtain full 
approval of any provisionally approved drug. Other than 
allowing the use of real world evidence to supplement an 
application, the PPA does not alter the current FDA standards 
for full drug approval in any way.
    The ALS story is slowly changing with--and with measures 
such as the PPA, we can make faster changes needed to finally 
get treatments to the community that will allow people such as 
myself to live longer and to potentially be around to see ALS 
transform from fatal to chronic.
    I want to take a moment to recognize the caregivers and the 
people living with ALS in this hearing room today. We represent 
the 30,000 Americans living with ALS right now. I hope you or 
your staff will take the time to hear their stories and why 
they believe in the need for the Promising Pathways Act.
    I also want to recognize Dr. Peggy Plews-Ogan who is before 
you as a witness and who has been living and breathing ALS and 
the

[[Page 8]]

PPA for the last year and a half. Thank you. Thank you for your 
time.
    Thank you for allowing me to be a part of this discussion 
and thank you for understanding how important the Promising 
Pathways Act is.
    The Chairman. I want to thank Brian and Sandra for their 
testimony and for being with us today. Now we will hear from 
Maureen Bell.

        STATEMENT OF MAUREEN BELL, GALACTOSEMIA PATIENT
              AND ADVOCATE, CHALFONT, PENNSYLVANIA

    Ms. Bell. My name is Maureen Bell. I am 51 years of age and 
I live in Chalfont, Pennsylvania. I have lived with 
galactosemia for my entire life. Shortly after my birth in 
1972, I began to show the classic hallmark signs of failure to 
thrive, jaundice, repeated vomiting, and weight loss.
    Seven days later, I was diagnosed by an intern as having 
classic galactosemia. I remained in the hospital for three 
weeks. My mom and dad were given a 32-page booklet entitled, A 
Parent's Guide to a Galactose Restricted Diet.'' They were 
instructed to follow this booklet as I would need to be on a 
lactose-free, dairy free diet for the rest of my life. That was 
the only treatment for galactosemia in 1972.
    I doubt my parents knew that many more challenges would lie 
ahead following the years to come than just having me follow a 
dairy free diet. It seemed that everything was working fine for 
me at the time, but I was getting older, and it made me feel 
very left out when I could not eat the same foods as my peers.
    Without modern day advances we have today in nutrition, I 
cannot tell you how isolating it was for me. There were many 
social events that I could not attend. My mom tried so hard, 
always sending me to parties with a special treat, not just for 
me, but enough for everyone so I was able to share.
    Not being able to eat the same cake that everyone else was 
eating at the birthday party as it just--was very difficult as 
a child. I also could not process information the same way. I 
always was a low average student and math was my most difficult 
subject, and still is today.
    I struggle with making change, leaving tips at a 
restaurant, and figure out--figuring out percentage. I cannot 
process it. Basic life circumstances became a struggle, and 
only when I met other people living with galactosemia did I 
realize that comprehension issues were similar for all of us. 
Just as I was slow academically, I was also slow in developing 
physically.
    While my friends were going through puberty, I was not 
having any issues of this. No normal signs of puberty or 
nothing like late development, and still--I still looked like I 
was in grade school physically, as opposed to being in high 
school.
    This continued and the sense of isolation also continued. I 
began to have unusual symptoms such as hot flushes, night 
sweats, and mood swings. After about a year of experiencing 
these symptoms and having bloodwork, I was diagnosed at the age 
of 18 as having premature ovarian insufficiency, which is a 
direct result of having galactosemia in female patients.

[[Page 9]]

    This was something that I--this is something that I 
continue to struggle with today. As a result of this diagnosis, 
I became very reclusive. I wanted no part in dating or 
socializing like any other 18-year-old would.
    That was the impact of POI, premature ovarian 
insufficiency. Secondary to having galactosemia, this was very 
difficult in my 20's. I just wanted to be like any other woman 
at my age, socializing and having fun.
    However, I was depressed and had a very difficult time 
making friends and meeting new people. There were nights that I 
cried myself to sleep. At a church event in 1999, I met a man 
named Bill who showed interest in me and started spending time 
with him.
    I was very apprehensive about getting involved in the 
relationship, even though I was 26 years old. The fear of 
falling for someone only to have to tell him that I was 
infertile and taking a chance on losing this relationship 
weighed on me very heavy. However, I finally got the nerve up 
to tell him.
    Bill is a pharmacist, and his response was priceless, not 
caring about my diagnosis and instead advising me to take my 
calcium because I was such a slacker at taking my calcium. What 
a huge weight that was lifted off my shoulders, and we recently 
celebrated our 23rd wedding anniversary.
    I was told that having galactosemia is like looking through 
a window at everyone at a party and eating--they are eating all 
kinds of foods that I cannot have. I could see them through the 
window and through the glass but could not break it or join 
them. The same is true for infertility. I can see moms, I can 
see children and families, but I cannot break the glass.
    This experience--I cannot break the glass but cannot 
experience what it is truly like to be a mom. All my life, I 
have longed to be on the other side of that window. There could 
finally be a treatment for people like me, and even though it 
is too late for me, for younger ones living the way I grew up.
    I spoke at the patient focused drug development meeting, 
but our community never heard from FDA after that. They had no 
questions, no clarification, and that made us worry they had 
not taken the time to learn from our work before reviewing the 
drug. Will they understand that speech issues don't matter to 
us the same way as cognition and developmental delays do?
    Some of us even have more scary symptoms than the ones that 
I have mentioned like seizures, kidney issues, tremors, 
cataracts, neurological impairments, and intellectual 
impairments.
    Will they understand that if they ask for another trial, 
rare diseases often don't have enough patients for another 
trial? Will they understand that if the drug is approved for 
something else rare, our doctors have seen the improvements in 
our community and will want to prescribe it for us to?
    The drug is already being studied in other rare diseases. 
Whether it is Government insurance or through my job, insurance 
companies don't treat rare diseases like cancer, so that is a 
whole other hurdle. These days we must fight for approval, but 
also fight insurance too.
    The Galactosemia Foundation is working hard on both things, 
and I hope you can help us all. I am learning about what places

[[Page 10]]

like FDA and CMS and Congress can mean to me and the others 
whose lives are impacted by diseases like galactosemia.
    I don't pretend to understand, but I know even one person 
can make a difference, and I want you to help the little girls 
with galactosemia going through isolation, the puberty, 
depression, and fear, the ability--the inability to understand 
and process. If all of you can make--can take my story and help 
them, it will mean so much. Thank you.
    The Chairman. Well, Ms. Bell, thank you for your testimony 
and for sharing your personal experiences with galactosemia, 
and we are grateful you are able to spend this time and hoping 
and listen to the whole hearing. We will now turn to our next 
witness, Dr. Plews-Ogan.

          STATEMENT OF MARGARET PLEWS-OGAN, MD, BRODIE

              PROFESSOR OF MEDICINE, UNIVERSITY OF

              VIRGINIA, CHARLOTTESVILLE, VIRGINIA

    Dr. Plews-Ogan. Chairman Casey, Ranking Member Braun, and 
the members of the Committee, thank you so much for the 
opportunity to present to you today.
    The testimony I give here is reflective of my own views and 
is not intended to reflect the positions of the University of 
Virginia. My name is Peggy Plews-Ogan, and I am first and 
foremost the wife and caregiver to my husband, Jim. We are both 
physicians. On December 2nd, 2021, our lives cracked open. Jim 
was diagnosed with ALS.
    At the time, we were both busy clinician scholars. Our 
lives were full with meaningful work, close family, a community 
of friends. With this diagnosis, our lives were completely 
upended. What I remember from medical school about ALS is that 
is a diagnosis that a physician dreads more than ever, more 
than any other.
    Why? ALS is a disease that robs a person of almost 
everything essential to living our lives, the ability to move, 
to communicate, to eat and drink, and eventually to breathe, 
but the double-edged cruelty is that awareness and cognition 
are left intact. People living with ALS can feel each loss and 
fear the next one every moment.
    ALS is 100 percent fatal. No one has ever survived. Average 
life expectancy after diagnosis is two to five years. When 
given this diagnosis, patients commonly hear, go home, hug your 
loved ones, and get your affairs in order.
    People worry about giving patients false hope, but I think 
they don't understand the devastation of having no hope, of 
simply waiting for the inevitable decline. Both being 
physicians, we were not naive about ALS, but having no hope was 
not an option for our family, so like many ALS families, we got 
moving.
    We read, we investigated clinical trials, we got involved 
in advocacy. One unacceptable reality we faced was that the 
disease moves faster than the FDA. AMX0035 was a drug in the 
pipeline that had excellent safety and better evidence for 
efficacy in a phase 2/3 trial than anything that was currently 
available, but it was initially denied approval by the FDA, who 
wanted an additional confirmatory phase three trial. This drug 
is a combination of two drugs that have been on the market for 
many years. One that was the counter. The only way to obtain 
the medication was to get the one component, Tudca is called, 
online, and the other component from

[[Page 11]]

a specialty pharmacy in New Jersey off label at a cost of 
around $1,500 to $3,000 a month.
    Most of our friends in the ALS community could not afford 
this. Only after fierce advocacy did the FDA take another look 
at the data and approve it, thankfully, over two years after 
the results of the clinical trial were clear. What does that 
two years mean for an ALS patient? Two years ago, Jim was 
running races.
    He was the chief medical officer for a new integrated care 
network for children across the State of Virginia. He started a 
new program at UVA to care for medically complex children. He 
had a thriving pediatric practice full of kids and parents who 
adored him. Today he is confined to a wheelchair. He needs help 
to eat.
    He cannot roll over in bed or even scratch an itch. He is 
losing his ability to speak. Inside the body that is failing 
him, Jim is the same brilliant, compassionate, creative, loving 
human being. The courage he displays every day is stunning. I 
am Jim's primary caregiver. The nights are the toughest.
    Every time Jim needs to turn over or adjust his vent mask 
to pull up the covers, I need to do that for him, and he needs 
to somehow communicate that need. Were it not for the support 
of our amazing grown children, extended family, neighbors, and 
dear friends, I am not sure what we would do. ALS is 
relentless. What do you think our life will be like in six 
months? One thing I know, Jim needs to be here.
    He has got a new grandbaby and a wedding to attend. As a 
physician, one of my areas of expertise is reducing errors in 
medicine. Doctors are naturally focused on getting all the data 
to make a certain diagnosis before we start treating someone, 
but we have learned over time that in rapidly progressive, 
life-threatening illnesses, delaying treatment while awaiting 
that certainty can cost someone their life.
    We start treatment while confirmatory data are coming in. I 
have watched helplessly as my husband lost the ability to use 
his hands, then his legs, then his voice. In the face of this 
100 percent fatal disease, delaying access to a safe, promising 
therapy until a confirmatory trial can be achieved is cruel. 
Jim and I are both old enough to have lived through the AIDS 
crisis.
    When I started residency, there were no treatments and the 
medical wards were filled with AIDS patients and their loved 
ones, the patients dying no matter what we did. Then patients 
and their loved ones got activated. They fought for more 
research funding.
    They fought for early access to therapies. I watched as 
each new therapy, one by one, turned the disease around. The 
earliest therapies were less effective and had more side 
effects, but they saved people's lives while new drugs were 
added and combined together into cocktails.
    Like those early HIV activists, we in the ALS community are 
fighting for more research funding. We are fighting for early 
access to safe and promising therapies. You have the power to 
change the landscape of ALS in this Congress, transforming it 
to a manageable and eventually a curable disease.
    This is not false hope. It is real hope. We need urgent 
action, and we are counting on you. Thank you very much.

[[Page 12]]

    The Chairman. Doctor, thanks very much for your testimony, 
and thanks for sharing your story and Jim's as well. Dr. 
Bhatnagar, you may begin your testimony.

               STATEMENT OF ANISH BHATNAGAR, MD,

                CHIEF EXECUTIVE OFFICER, SOLENO

             THERAPEUTICS, REDWOOD CITY, CALIFORNIA

    Dr. Bhatnagar. Chairman Casey, Ranking Member Braun, and 
honorable members of the Committee, I am honored to testify at 
today's hearing. Thank you for inviting me. My testimony today 
is my personal opinion based on my experience over the years. I 
am a physician by training.
    My 25-year career almost entirely at small companies has 
involved developing treatments for cancer, for neurological 
psychiatry, cardiovascular, and other diseases, and for the 
last several years for rare diseases.
    None of my work, including that on life saving cancer 
drugs, has been as meaningful as working with this amazing 
community of families who have children and adults with Prader 
Willi syndrome.
    Many of them are in the audience today. While the 
regulatory challenges across therapeutic areas are similar, 
there is a much more disproportionate impact on patients with 
rare diseases. A similar disproportionate impact is seen on 
small companies like ours, which do a large proportion of the 
high-risk work.
    Our ability to raise money and continue work depends 
predominantly on regulatory clarity. If the minutes of an FDA 
meeting do not clearly State a path forward, or if a company 
receives inconsistent feedback, it could be the difference 
between having money to carry out a pivotal trial or giving up 
on a drug to treat a disease that has no options.
    Speaking of diseases with no options, Prader Willi 
syndrome, PWS, is a rare and life threatening genetic condition 
which occurs randomly and affects about 10,000 to 20,000 
patients in the U.S.
    Children with PWS are often recognized within weeks of 
birth. By the age of three or four years, they would start to 
show more of an interest in food, which increases over time 
until they ultimately developed a hallmark symptom of 
hyperphagia, an insatiable desire to eat, the brain telling you 
that you are starving even as you eat.
    Individuals affected by PWS never feel full and are 
constantly focused on one thing, food and how to get it. Left 
unsupervised, they have the potential to literally eat 
themselves to death. Much like a teenager with PWS who recently 
ran away from home, ate enough that his stomach ruptured, and 
he passed away.
    The only remedy for hyperphagia is to restrict access to 
food, close kitchens, lock refrigerators and pantries, motion 
activated cameras and alarms. Families live in the constant 
fear of extreme outcomes like visits to ERs, police 
intervention, and in many situations, the need to be cared for 
in an institutionalized setting. Invariably, there is a need 
for constant supervision for life.
    Numerous drugs have been tried, tested to treat hyperphagia 
and PWS in late-stage trials. Each one of them has failed and 
many companies have been dissolved. Our drug, DCCR, is a once-
a-day pill based on a known parent molecule, which was 
evaluated

[[Page 13]]

in an approval directed study from 2018 to 2020, ending a few 
months after the start of the COVID-19 pandemic.
    The study missed its primary endpoint, but the analysis of 
the pre-COVID data showed statistical significance in favor of 
the drug. Long term data, now up to four years in some 
patients, and comparisons to natural history of the disease 
show statistically significant and clinically meaningful 
improvements with the drug.
    We have been asked to generate additional controlled data 
before submitting a marketing application to the FDA. We have 
just completed the study, which shows highly statistically 
significant and clinically meaningful benefits of DCCR, and we 
hope to submit an NDA to the FDA next year.
    We need a regulatory framework that recognizes the novel, 
complex, and heartbreaking nature of diseases like PWS. We 
cannot continue to apply the same regulatory paradigm to all 
diseases and all drugs. Context must play a role. It is amazing 
to see new options available for people with ALS and the first 
approval of a drug for Friedrich's Ataxia, but there is also 
diseases like Barth syndrome, where a drug with promising data 
may not have a path forward. Regulatory delays such as the 
three plus a year back and forth with the FDA have real life 
impacts. For companies like ours, programs will be cut. Some 
will even shut their doors.
    Every day, every week, every month, every year symptoms 
will worsen, sometimes in irreversible manners, and patients 
may even die as they wait for treatments. The FDA is and needs 
to remain the premier regulatory body of its kind in the world. 
What is desirable is a rigorous regulatory process, but one 
that balances the risk of approving a drug with the risk of 
having no treatments available for a desperate population.
    The Promising Pathway Act is a significant step in the 
right direction. Time limited provisional approval would allow 
patients the ability to access potentially life changing 
treatments, as additional meaningful data is generated to 
justify their use.
    Availability of such treatments would be driven by 
clinically relevant data, and final approval would come only 
upon rigorous analysis of data generated from patient 
registries. In closing, I truly appreciate the opportunity to 
share Soleno's story, highlight the significant unmet needs of 
the rare disease communities, in particular the PWS community.
    Thank you for your time. I look forward to your questions.
    The Chairman. Doctor, thanks very much for your testimony. 
Next, we will move to Professor Fernandez Lynch for your 
testimony. You may begin.

          STATEMENT OF HOLLY FERNANDEZ LYNCH, JD, MBE,

             ASSISTANT PROFESSOR OF MEDICAL ETHICS

              AND LAW, UNIVERSITY OF PENNSYLVANIA,

                   PHILADELPHIA, PENNSYLVANIA

    Mrs. Fernandez Lynch. Thank you. Thank you for the 
opportunity to inform today's discussion about how best to 
achieve a goal we all share, helping patients with rare serious 
diseases live better and survive longer.
    My name is Holly Fernandez Lynch. I am an Assistant 
Professor of Medical Ethics and Law at the University of 
Pennsylvania, speaking only on my own behalf. As you heard, my 
scholarship fo

[[Page 14]]

cuses on FDA drug approval policy, access to medicines prior to 
FDA approval, and clinical research ethics and oversight.
    I sit before you as an academic on a panel filled with 
lived experience, in a room filled with lived experience. I am 
not personally living with a rare, serious disease, but the sad 
reality is that rare diseases are not rare in the aggregate.
    Any one of us could find ourselves or our loved ones 
affected at any time, and like many, my family has not been 
spared from serious and life-threatening diseases, including 
Parkinson's and childhood cancer. We all have an interest in 
these important issues, whether we are suffering today or may 
be suffering tomorrow.
    My key message to the Committee is that weakening FDA's 
approval standards risks conflating the essential goal of 
getting patients access to more drugs that work with the 
deflated goal of simply getting them more drugs. Of course, we 
should tolerate more uncertainty when considering drugs for 
serious diseases.
    Thankfully, FDA already has expansive regulatory 
flexibility, allowing it to do just that. The agency is 
granting accelerated approvals more frequently and more broadly 
than it has in the past. It has also demonstrated willingness 
to approve drugs when trials fail to show benefit on pre-
specified endpoints, when benefit is supported by just one 
pivotal study, when trials are very small, and when they lack 
concurrent control groups.
    Unfortunately, this flexibility is not always met with 
rigorous confirmation of benefit after drug approval, which is 
a concern also raised by the Promising Pathway Act. The 
proposed bill has some important strengths.
    For example, it seeks to limit how long drugs with 
uncertain benefit can stay on the market, and it emphasizes 
that uncertain drug approvals should always be followed by 
efforts to collect additional evidence. However, I fear that 
the Promising Pathway Act would set the bar too low for both 
provisional approval and later confirmation of benefit.
    Now, I certainly understand why any individual patient 
might be willing to pursue access to a new drug based on 
relevant early evidence of a positive therapeutic outcome, the 
bill's proposed standard. The problem is that weak approval 
standards affect all patients, not only those who choose to 
take a provisionally approved drug.
    Companies produce evidence about safety and effectiveness 
because it is a legal requirement for marketing and to profit 
from their drugs. If FDA demands less evidence, patients and 
clinicians will have less evidence.
    We see this today in the dietary supplement industry, but 
imagine if what you had available to treat your life 
threatening illness was rows and rows of products, none of 
which were known to work.
    Weak approval standards can also entrench poor treatments 
by making it difficult to study potentially better treatment 
options, both because of reduced willingness to enroll, and 
challenges interpreting results when new drugs are compared to 
unproven ones.
    The Promising Pathway Act proposes to address these 
challenges by relying on patient registries, but because 
registries lack randomization and blinding, observed 
differences in outcomes might be at

[[Page 15]]

tributable to underlying differences between patients rather 
than a result of the drug of interest.
    Instead of weakening FDA's already flexible approval 
standard, the stronger path forward is to address scientific 
bottlenecks. FDA and others have already taken important steps 
in this direction.
    The agency recently launched a program informally dubbed 
Operation Warp Speed for Rare Disease, which will provide real 
time advice to companies starting at the earliest stages of 
drug development to speed successful trials, address 
manufacturing issues, and other challenges.
    The agency also has a pilot program to advance development 
of new end points for rare diseases. Its action plan for rare 
neurodegenerative diseases and its ALS science strategy 
emphasize improved scientific understanding of rare disease, 
enhance clinical trial infrastructure, and innovative trial 
designs to support the development of better drugs.
    While the science continues to develop, the best way for 
this Committee to improve access to effective rare disease 
treatments is by ensuring adequate funding for rare disease 
research, promoting clinical trial accessibility, encouraging 
use of FDA's expanded access pathway, and clarifying that FDA 
has the authority to require and enforce rigorous post market 
efficacy studies whenever it approves a drug with uncertain 
benefit.
    Thank you for your commitment to these important issues and 
I look forward to your questions.
    The Chairman. Professor, thanks very much, and our sixth 
and final witness, Mr. Desserich.

                 STATEMENT OF KEITH DESSERICH,

            CHAIRMAN/CO-FOUNDER, THE CURE STARTS NOW

          FOUNDATION, PRESIDENT, PEDIATRIC BRAIN TUMOR

            CONSORTIUM FOUNDATION, CINCINNATI, OHIO

    Mr. Desserich. Thank you, Chairman Casey, Ranking Member 
Braun, and distinguished members of the Committee for the 
opportunity to discuss the Promising Pathway Act. It is 
something that I consider vital to our efforts to find the 
homerun cure for cancer. I am Keith Desserich.
    I am Chairman, Co-Founder of The Cure Starts Now 
Foundation, Board Member of the DIPG-DMG Collaborative, I am 
President of the Pediatric Brain Tumor Consortium, but most 
importantly, I am a father.
    My daughter, Elena, fought a cancer called DIPG when she 
was just six years old. We had no hope. There were no trials 
available, and they told us to go home and make memories. 
Sadly, she understood this as well, fully aware until her very 
last day that there was nothing that we could do.
    You see, with DIPG, each day you see your child lose 
something. One day, it was her ability to be able to see out of 
her left eye. The next day it was her ability to speak. Then 
her ability to walk. Until one day it became her ability to 
swallow, to breathe, and her heartbeat. What is particularly 
cruel about this type of disease is that it affects children, 
and it is very, very rare in adults, but at the same time, many 
experts believe that this is a cancer that can show the most 
promise, at the same time is believing that this is

[[Page 16]]

a cancer that they fear most. Universally, for this reason, it 
is known as a home run cure cancer.
    We have made it our mission to focus on these rare cancers, 
building tools from scratch, such as a registry that spans 129 
hospitals, intelligent patient tools, strategic research, and 
even virtual hospitals to try to leverage all of the great 
guidance and intelligence that we can find worldwide to come to 
bear on one specific patient, and in the 17 years since Elena 
lost her fight, we have invested in over $30 million in 
research and support through 135 projects. I understand the 
perspectives of the researcher. I understand the perspectives 
of the parents. I understand the perspectives of the registry.
    I come to you having seen each of these various elements of 
it, in addition to talking with parents each and every day when 
they are in their last weeks. I also come to here with hope. I 
hope for a new way to fight cancer. I believe that the FDA is 
well-intentioned, but in the end, no one plans for this type of 
devastating cancer.
    Sadly, I believe that there is much confusion inherited 
from bureaucracy, and whether by regulation or guidance 
clarity, I argue that the system is broken, and the status quo 
will not do. For our purposes, there are effectively only two 
measures that we can consider when we start to talk about DIPG.
    One is expanded access, and the other one is Right to Try. 
It is important to note that with expanded access or 
compassionate use, it is not an alternative for the Promising 
Pathway Act. I know this not only from dealing with the loss of 
my daughter, but also in calls with over 200 families per year 
asking for help, any help in their last and final days.
    With DIPG, a patient is frequently only given two weeks 
after progression to act. Expanded access requires four levels 
of approval, 24 hours for a family to reconcile with the news, 
three days for a doctor to determine the strategy, two weeks 
for an internal review board to approve a methodology, three 
days for a pharmaceutical company to respond, and up to 30 days 
for the FDA to effectively approve the entire process.
    That is one week longer than our child survives. It doesn't 
work. Then there is Right to Try. It is slightly better with 
the two-level approval process, but it lacks data transparency 
to patients and families with an annual report model that 
submits to the FDA. We think clarity, we think transparency are 
cornerstones of being able to find the cure.
    All of these, though, and the current guidelines assume 
that terminal means months or years to live. They assume that 
patients are not intelligent to make decisions for themselves. 
They assume that data in less than ideal situations are 
worthless, and they assume that every patient is an adult, and 
the assumptions are wrong.
    The reality is we don't get doctors that understand the 
systems. We don't get a call back on the weekend, and none of 
these acts were designed for pediatric terminal diseases. The 
Promising Pathway Act is different.
    It offers an alternative to FDA mandated unethical practice 
of trials, giving the wrong drug to the wrong patients for 
pediatric

[[Page 17]]

terminal diseases. Right now, nearly every therapy designed for 
pediatric cancer is guided through a three-phase adult trial 
before we can even get to try it on a terminally diagnosed 
child.
    Sadly enough, some of these cancers don't even affect 
adults like DIPG, meaning that we either misapply a trial on 
the wrong patients, or worse yet, the drug company simply gives 
up. Now remember that some of our biggest advances in cancer 
started with pediatric cancer. You want to know why we can't 
advance a cure? This is why.
    The PPA also preserves critical data on outlier 
participants in a trial and retains it for the use by the FDA, 
the drug companies, the researchers, and the patients in any 
third-party registry of substance thus improving transparency. 
PPA also addresses insurance coverage and financial burdens in 
ways that neither previous alternative has.
    Finally, the PPA, or promising Pathway Act, advances 
innovative therapies that may be impossible to subject to 
current trial design. Keep in mind that trials for rare cancers 
rarely ever get full accruals, leading us to either give up on 
good ideas or enrolling children in older trials that we 
already know don't work. It is not lost to me the value of a 
clinical trial, but what is lost to many others is the value of 
a quick and efficient clinical trial.
    Unfortunately, with rare pediatric cancers, we have to 
consider both this, and sadly in their final days, we also have 
to consider compassion. I have this pile in front of me of 
grants. These are grants that we have worked to build, to fund 
at many different institutions. There is 46 of them.
    This is a pile which has hope. This is a pile which is the 
dreams of the researchers, and frankly, it could be the lives 
of these kids. This is 46 chances to be able to cure cancer, 
and sadly, the whole reason why I am here today is because I 
believe that these 46 opportunities to be able to cure cancer 
may never reach bedside unless we get PPA passed.
    I am a big believer in personal initiative, but in this 
case, we may be able to go no further unless Government gets 
out of the way. The Promising Pathway is how we do this. 
Families are desperate for another chance, a chance to see 
their children go to kindergarten, a chance to see their child 
get a driver's license, a chance to see them graduate from high 
school, a chance to see them go to college and get married.
    We want a chance to see them grow up. Rarely do you have a 
chance or a bill that asks for no money, and the money is not 
really part of what we are asking for. This is that rare case 
when you can act to give patients fighting for the lives the 
power to save their own lives. I lost my daughter, but I refuse 
to believe that we cannot save others.
    You have heard today from some very compelling and well-
educated witnesses. I am the only one, however, that has lost 
everything in this and was given no options because there 
wasn't any. There was existing barriers that were either too 
cumbersome or our policies were built around the majority, and 
while some of these numbers may appear small from the 
aggregate, in the end, it is not--it is with this type of 
cancer that experts also believe

[[Page 18]]

that we all have the greatest impact to be able to cure it, and 
so what we may ignore may be precisely what must save us.
    The Promising Pathway Act may be the single biggest piece 
of legislation that costs nearly nothing but may change 
everything about how we win this war against cancer. Thank you.
    The Chairman. Mr. Desserich, thanks so much for your 
testimony and for sharing the story of your family and your 
daughter.
    Mr. Desserich. Thank you.
    The Chairman. I will now turn to Ranking Member Braun to 
begin a round of questions.
    Senator Braun. Thank you, Mr. Chairman. First question is 
for Brian Wallach. Brian, if you are still with us here on 
Zoom, we appreciate your testimony earlier, and because of your 
work, you have got so many people engaged in the cause and 
kudos to you for that.
    Question, what would your risk tolerance be for a new 
therapy that has documented, real world evidence showing 
efficacy and has received provisional approval from the FDA?
    [No response.] We will come back to Brian if he is still 
with us on Zoom.
    The Chairman. I think----
    Senator Braun. Go ahead, Brian.
    The Chairman [continuing]. delay----
    [Technical problems.]
    Mrs. Abrevaya and Mr. Wallach. Thank you, Senator, for your 
question. As a patient who has lived six and a half years with 
ALS, I have no other options for new treatments other than--
other than the expanded access program or provisional approval, 
and as my disease is 100 percent fatal right now, I am willing 
to take risks that other patients may not be. I know that if I 
do not try--I know that if I do not try safe, promising 
treatments, I will die.
    As Peggy said, we know that each treatment does not make a 
cure, but together they can create a cocktail similar to what 
we had in HIV that will keep me alive and turn ALS from fatal 
to chronic.
    My simple answer is that ALS patients are willing to accept 
greater risk because we know what is behind door number two.
    Senator Braun. Thank you, Brian. Next question will be for 
Mr. Desserich. Thank you for sharing your story. Sorry for the 
loss of your daughter. Your advocacy, you know, of course, 
means a lot to her and her legacy. Do you feel that any kind of 
drug approval or access programs at the FDA address rare, 
terminal pediatric cases like DIPG?
    Mr. Desserich. I don't. That is the reason I am here. I am 
here because there isn't anything that applies to this.
    I mean, the amount of patients that we talk to that are 
reaching out to us, and they are reaching out to us partially 
because they are not getting any answers from medicine or drug 
companies or anything of that sort, or it is impossible at that 
point, and it is because of really two things.
    One reason is because of time. We don't have that time. We 
have two weeks. Nothing gets done in those two weeks. I have 
had so many times where I have seen a compassionate use has 
been approved for a patient, but it usually comes in several 
days after the patient has already passed.

[[Page 19]]

    You want to talk about a difficult call, that is a horrible 
call to make. I have also seen where it doesn't address 
anything having to do with pediatric. We write laws with the 
idea of adults, and if you look at any of these guidelines that 
we have put forth through the FDA, we grant waivers for them 
not to do it in pediatrics, but we never go the opposite way, 
and so, because of that, we have to wait, and we have to hope 
that it can go through all of the adult trials first before it 
can ever get to a child trial, and so, it never gets started, 
and so, at the end of the day, we can't get access to those 
drugs.
    The time is not the right amount of time, and the children 
are being ignored in this and it shouldn't be that way.
    Senator Braun. Thank you. I yield back. I do have more 
questions. Back to Chairman Casey.
    The Chairman. Senator Ranking Member Braun, if you want 
to----
    Senator Braun. Go ahead?
    The Chairman. You want to, ask another one. You still had 
about a minute, so.
    Senator Braun. This question will be for Dr. Plews-Ogan. 
FDA has a variety of drug approval pathways and designations. 
In recent years, the agency has begun to take steps toward 
creating a more accessible and flexible system.
    However, millions of Americans with these diseases still 
lack any FDA approved treatments. Could you highlight the holes 
in the FDA's drug approval and clinical trials system that your 
husband James has fallen through?
    Dr. Plews-Ogan. Thank you for that question, so I will just 
mention two. One, I think we have heard a lot about today, and 
I want to be really clear that that problem is really important 
to me, and that problem that I would like to see solved is that 
patients who are dying don't have timely access to promising, 
safe therapies. Just to be clear, I don't think anyone you have 
heard speak is suggesting a change to the safety standard.
    This is about time. It is about access. The FDA process 
involves, first of all, early trials to establish safety, phase 
two trials to confirm safety and establish potential efficacy, 
and then phase three trials.
    The phase three confirmatory trials to confirm efficacy can 
take an additional four to eight years. These are years 
obviously, that no one on this--sitting at this table has had 
for themselves or their loved ones. The time it takes for these 
confirmatory trials is simply too much for these particular 
patients with these particular diseases, so we want access to 
promising therapies when early evidence has been established 
and is being confirmed.
    All we want as an alternative to certain death is a pathway 
that allows us access to these therapies at the point where 
safety and promising evidence and effectiveness have been 
established. The second point I want to make is that there's 
been a lot of talk about the accelerated pathway.
    Accelerated pathway is really not available to patients 
with ALS at this point, at least 95 percent of patients with 
ALS, because there is no reliable biomarker, and the 
accelerated pathway requires or relies on biomarkers or 
surrogate endpoints, so that is an

[[Page 20]]

other huge hole for someone like Jim. That pathway really 
doesn't apply.
    Senator Braun. Thank you. This question is for Dr. 
Bhatnagar on biotech risk. On these diseases, mostly smaller 
companies address them. Could be billions of dollars, years to 
submit a new drug application to the FDA. Larger companies 
generally don't do it. Tell me a little bit about is the market 
cooling for this due to the fact that we have got a process 
that is stubborn and bureaucratic?
    Dr. Bhatnagar. Thank you, Senator, and the answer is yes. 
There are parts of the biotech ecosystem that are doing well. I 
mean, science is robust. Patient advocacy is stronger than it 
has ever been before, but what is cooling is the funding 
environment, and you can see that if you look at the XPI, which 
is, you know, a gauge of public companies. It is down more 
than--about 30 percent this year.
    This may be the third year in a row it is down, at a 
stretch which would be the first time that is the case since it 
was first conceived. Number of companies going under has been 
phenomenal. Number of layoffs has been extraordinary, so yes, 
the ecosystem----
    Senator Braun. Would the Promising Pathways Act address 
that in a way that would be meaningful, so we at least keep 
businesses in business to try to work on these ailments?
    Dr. Bhatnagar. I think so. When you think of why that is 
the case, I think the uncertainty in the regulatory environment 
is a big factor for rare disease companies. Companies like 
mine, we work on one or two programs, and if you don't have the 
clarity, then it is hard to get the funding to do the work, so 
yes, if there is a pathway that is more certain, it would 
definitely help.
    Senator Braun. Thank you. I yield back.
    The Chairman. Thank you, Ranking Member Braun. I will next 
move to my questions. I also wanted to note. We obviously have 
a number of Senators who have been here. Some have been here 
and won't be back.
    Some will be back, but after my questions, in order of 
appearance, we will go to Senator Scott. We have also had 
Senator Gillibrand, Senator Blumenthal here, and let me just go 
to my first maybe two questions.
    Dr. Bhatnagar, I wanted to ask you a question, but as a 
predicate for that, I understand that one of the challenges in 
rare disease drug development is that there are often very few 
true experts in the disease and that this presents difficulties 
at different stages of the drug review process.
    FDA has acknowledged these challenges and indicated they 
are open to revising some of the policies to ensure clinical 
expertise for rare disease therapies, so doctor, here is my 
question.
    As you have worked through this drug development process, 
are there areas where greater expertise in rare diseases like, 
as you mentioned, PWS, Prader-Willi syndrome, among FDA 
expertise for that syndrome among others, among those FDA 
reviewers, are instances where that would be helpful, that 
greater expertise?
    Dr. Bhatnagar. Thank you, Senator, and yes, it would be 
helpful. When you are dealing with a disease like Prader-Willi 
syn

[[Page 21]]

drome, we don't expect that there would be expertise at the FDA 
because it is a rare disease.
    We would hope that there is that understanding, and the 
idea that from the very beginning of the process, there would 
be experts at the other end. That has not been the case. We 
generally take physician experts with us, but unfortunately, 
they are considered to be conflicted.
    The problem in rare diseases, which is very different from 
other large, mass market type of diseases, is that you 
generally involve all experts in the clinical trials, otherwise 
you would not be able to enroll those trials, so if you believe 
them to be conflicted, then who would be the expert?
    I think this is one not very difficult thing that can be 
implemented, and you can take that opinion with a grain of 
salt, but at least consider them to be not conflicted and 
speaking for the disease.
    The Chairman. Doctor, thanks very much. I just have one 
more question before I turn it to Senator Scott. Professor 
Fernandez Lynch, how can the FDA ensure it is consulting with 
these appropriate disease experts, while also ensuring 
transparency around say potential conflicts of interest during 
the review of products for rare diseases?
    Mrs. Fernandez Lynch. Thank you, Senator, for the question, 
so this comes up very often when FDA is trying to populate the 
advisory committees of external experts that it often calls 
upon to help them understand various issues related to whether 
or not they should be approving products, as well as broader 
questions about drug development in particular areas.
    FDA can waive, you know, the conflicts in certain 
circumstances, for example, where there is a dearth of experts 
in a given area, and they often do waive the typical conflict 
of interest rules. There are other ways also of managing 
conflict.
    For example, if you include somebody who has ties with 
industry or has participated in trials, you can also invite 
additional people to provide their broader perspectives, so I 
think this is already something that is happening at FDA.
    They are well aware of the challenge, and in fact, it is 
more often academics like myself who are pushing FDA to be more 
careful about conflicts than they already are.
    The Chairman. Thank you, professor, and I will move to 
Senator Scott.
    Senator Rick Scott. First, I want to thank the chair and 
ranking member for putting together this hearing.
    I thank everybody for being here. I want to thank all of 
our witnesses. I think everybody in this country has probably 
been impacted--has somebody who has been impacted by a rare 
disease, and in health care, they have either impacted by 
something that they did not had access to, or if they did, the 
difficulty of affording the health care in this country.
    It is really tough. I built a hospital company and your 
just heart goes out to people. How expensive things have also 
gotten on top of the regulatory hurdles you go through, so my 
first employee in my hospital company actually had and passed 
away with ALS, and it is a devastating--it is a devastating 
disease, so your heart goes

[[Page 22]]

out to anybody that has it. One thing I did as Governor of 
Florida is I--when I was Governor, we got all of our, all the 
money--we dramatically increased our research dollars on cancer 
and we got to all of our cancer centers, and everybody was 
doing research and say they got money, they had to share all 
their data which--to accelerate it, and that seemed to have 
some impact.
    We have put a lot of money into NIH. In the 2000's I think 
we doubled the budget of the NIH, but clearly cures haven't 
come out, so I think we have to just do what all of you are 
saying, rethink what we are doing to see if there is something 
better we can do, and this is--I am glad you are here because 
this is how we get things done by getting--by people telling 
their stories, and so, because of your story, you can come up 
with how you can try to solve it, so Dr. Bhatnagar, what can 
Congress do to expedite the delays that you are seeing?
    Dr. Bhatnagar. Thank you, Senator. First, I want to just 
acknowledge that Florida is the epicenter of PWS care in the 
world. The University of Florida has a physician by the name of 
Jennifer Miller, who sees the largest population of PWS 
patients in the country.
    To answer your question, it is probably true that the FDA 
already has the authority needed to provide regulatory 
flexibility in the circumstances that we are talking about. 
Unfortunately, there is no consistent application of that 
flexibility.
    I don't know what tool it takes, but I think to mandate the 
consideration of regulatory flexibility in all rare disease 
applications is valuable. I think to work with experts to 
define for a given disease setting what that flexibility should 
look like is important, and then to come up with an enforcement 
mechanism to ensure that it is happening is important. I am not 
sure what tool it takes, but I think conceptually that is how I 
would go about it.
    Senator Rick Scott. Yes. Well, in May of this year I joined 
with 24 my colleagues in both the Senate and the House asking 
for change at the FDA. We requested a task force be developed 
to include leaders from all divisions, offices, and centers 
which process rare disease therapy applications to fully 
examine areas of policy and procedural inconsistency and 
shortcomings to see what we can do better.
    We also asked that the task force provide Congress 
recommendations. The FDA disagreed with our request to form a 
task force. They said they were going to share relevant 
reports. I think a lot of times up here people do have the 
authority to do the right things. It is just the way the 
process is set up, and then there is no accountability, that it 
doesn't work the way it is supposed to work.
    The more specific you guys are to any of us, the greater 
chance we are going to be able to get something done. Do any of 
you know what type of patient experience the FDA collects in 
its clinical trials, and how does the FDA use that? Does 
anybody have any ideas?
    Dr. Bhatnagar. I think patient experience is going to be 
collected in a variety of ways. One of the newer mechanism 
which the FDA has been using is a patient focused drug 
development meeting

[[Page 23]]

where the FDA attends and listens to the patient populations 
about the unmet needs, etcetera.
    During trials, in trials like ours, we collect patient 
information based on questionnaires, looking at symptoms and 
signs that are relevant, so the agency definitely has a lot of 
that evidence in their hands.
    Real world evidence is something that they have been 
discussing, but it has been part of very small number of 
applications for approval, and it is certainly not been the 
primary way any drug has been approved so far. Dr. Lynch, if 
you have something to add.
    Mrs. Fernandez Lynch. Just to add onto that, importantly, 
of course, it is not FDA that is gathering the evidence, right. 
It is companies that are responsible for conducting the 
research, but through the patient focused drug development 
program at FDA, they have put out several guidance documents to 
promote systematic methodologies in gathering patient 
experience data to inform the development of clinical trials, 
to make sure that they are asking the questions that are 
important to patients, and systematically gathering information 
so that it can inform regulatory decisions.
    FDA also has made great strides in incorporating patient 
perspectives. For example, having patient representatives on 
advisory committees.
    Senator Rick Scott. Yes. Thank you. Thank you, Chair.
    The Chairman. Thank you, Senator Scott. Ranking Member 
Braun.
    Senator Braun. I think from the discussion you have heard 
today that it is clear that there is a difference between the 
broad array of diseases out there, the places where most 
pharmaceutical companies go, and that with everything we are 
talking about here, it is just not being addressed.
    Keith, I would like you to comment on, is the paradigm that 
we have currently, working, especially in the case of one with 
a narrow window of survival? Within the paradigm that is to me 
bureaucratic, it has not responded in a way to these over a 
long period of time, what--is there any hope that we can get it 
done within that current structure?
    Mr. Desserich. I think that the comments that we were 
talking about of, you know, what is being collected and also 
comes down to, you know, the guidance as opposed to 
regulations, and, you know, as was pointed out, you know, the 
idea that it probably could be done in the right way, but 
unfortunately it isn't. I think that there is a lot----
    Senator Braun. Is that called compassionate use in the 
current framework?
    Mr. Desserich. Yes. I mean, I guess it could be. I mean, 
but I mean you could--they could take any of these measures and 
they could probably try to--with it, but it doesn't happen.
    I think that is the reason why PPA really needs to be there 
is because otherwise without it, there is nothing that is going 
to make sure that there is any accountability to deliver the 
right decision on it. You know, we witnessed it time and time 
again. I have talked to drug companies, and they tell me they 
can't figure it out.

[[Page 24]]

    They feel that, you know, what is in the guidelines versus 
what is in the guidance or the suggestions that they receive 
back is not matching up. You know, I talked to a drug company 
just last week and they said they are probably not going to be 
focusing on our realm and on pediatric drugs because----
    Senator Braun. That is why we need the formality of PPA.
    Mr. Desserich. Exactly. They see no way that it is going to 
work, and, you know, they are giving up, and we can't have 
that. You know, these are small drug companies, but that is 
where sometimes the best ideas come from, and if we take away 
the opportunity to consider those good ideas, that is a 
problem.
    I think the other thing that we miss is really the patient 
right type of thing. We talk about data collection. We talk 
about the idea of being able to have it at the pharmaceutical 
level or in the FDA. Data isn't the property of one entity over 
another.
    You know, there has to be also a patient element to this. 
That is the beauty of what is in the Promising Pathway Act. Is 
also the international register or these registries that are in 
there, these independent registries, which allow for everybody 
to be able to communicate that, but still protect the patient 
privacy at the same time, and you know, otherwise we are just 
going to get half of the information.
    We are going to be following what we think is necessarily 
the guidance on it, and effectively, what we are left with is a 
Wild West type of mentality as to how we deal with drug trials, 
and we can't keep doing it that way because if that is the 
case, we are never going to be able to get anywhere on this.
    Senator Braun. Thank you. I yield back.
    The Chairman. Thank you, Ranking Member Braun. Senator 
Warren.
    Senator Warren. Thank you very much, Mr. Chairman, and I 
want to say I very much appreciate Senator Braun holding this 
hearing and advancing this important idea. For individuals who 
are experiencing a devastating diagnosis, the promise of a new 
therapy or a cure provides hope in a profoundly dark time, and 
that is why I have long described Federal support for medical 
research as one of the best investments that our Nation can 
make and why I have introduced legislation to ensure that we 
fully invest in medical breakthroughs.
    I want to, if I can today, talk about just a slightly 
different part of what happens in the drug approval process 
that I am concerned about. I want to talk about how we get 
research from the lab to the pharmacy, and one of the key parts 
of that, as many of the people in this room know, is clinical 
trials.
    Once a promising therapy is identified, pharmaceutical 
manufacturers have to test the drug for safety and 
effectiveness, which involves enrolling patients in clinical 
trials. Patients place enormous trust in the people running 
clinical trials, which is why all research involving human 
subjects in the United States must be approved by institutional 
review boards or IRBs.
    Professor Fernandez Lynch, you lead work on the quality and 
effectiveness of IRBs. Can you just say a little bit more about 
what the job of IRBs actually is?

[[Page 25]]

    Mrs. Fernandez Lynch. Of course. Thank you, Senator, for 
the question. IRBs have been required to review nearly all 
federally funded research and federally regulated research for 
several decades now, and their responsibility is to protect the 
rights and welfare of people who participate in studies by 
making sure that the risks and benefits of research are 
appropriately balanced and that there is adequate informed 
consent, they prevent ethically problematic research from 
proceeding, and they also help make sure that the science is 
strong.
    When people are giving their time and energy to 
participating, that is an important element of trust, and they 
shouldn't be exposed to unnecessary burden and risk, but then 
IRBs also have a very important responsibility to facilitate 
high quality research and to promote ethical research to answer 
questions that will benefit patients and society.
    Senator Warren. All right, so as I understand this, if a 
clinical trial can't answer the questions it sets out to study 
or doesn't properly communicate the risks of the study to the 
people who participate in it, then it is the job of an IRB to 
step in and keep patients safe, but rapid consolidation and 
private equity ownership of IRBs has raised some serious 
questions about whether these boards are leaving vulnerable 
patients exposed to unnecessary risks. Now, while most IRBs are 
affiliated with universities, IRBs that are not associated with 
any institution, they are known as commercial IRBs, are 
reviewing a larger share of drug clinical trials.
    According to a recent GAO report, despite representing just 
two percent of the review boards, these commercial IRBs now 
review over half of studies involving investigational new 
drugs, and 92 percent of them are reviewed by just two private 
equity backed companies.
    The GAO reported that private equity backed IRBs, I am 
going to quote here, ``are beholden to their clients or equity 
holders.'' In other words, the people who put the money up. 
Professor Fernandez Lynch, what are the risks that this creates 
for clinical trial participants?
    Mrs. Fernandez Lynch. Thank you, Senator Warren, and I very 
much appreciate that you pushed the GAO to examine this issue. 
I wasn't surprised by their finding that we still lack 
meaningful measures of IRB quality. This is something that has 
come up time and time again, and the lack of our ability to 
assess quality meaningfully makes it hard to comparatively 
assess these different types of IRBs, which is a problem that I 
am working on in my own research.
    One challenge and concern about private equity ownership 
and profit oriented goals in the IRB space is that it creates a 
primary emphasis on speedy approvals of proposed research and 
keeping the sponsor happy, and that emphasis on speed also kind 
of trickles down from the private equity IRBs to the university 
IRBs, who have to compete with them. Now, of course, speed can 
be a very good and important thing when we are talking about 
research. We want high quality research to move quickly.
    Focusing on speed can also inhibit deep attention to 
ethical concerns, and it can also limit the focus on maximizing 
scientific quality and really just approving science that is 
good enough, kind of

[[Page 26]]

meets the floor of regulatory requirements, rather than making 
sure it is maximally valuable, and so, I think that is a 
primary concern here.
    Senator Warren. I appreciate you raising this because I 
just want to make sure we get this right. You know, the GAO 
found that an emphasis on profits can lead private equity 
backed IRBs to rubber stamp reviews of drug clinical trials and 
focus less on potential harm to research subjects.
    While HHS and FDA are responsible for inspecting IRBs to 
ensure that participants are protected, the number and 
frequency of these inspections has been steadily decreasing, so 
HHS and FDA need to step up their oversight efforts in this 
area, and that includes clarifying what it means for an IRB to 
be working effectively, something that these agencies have 
never done despite years of decades of requests, so that 
clinical trial participants have complete confidence in the 
scientific integrity of the trials that they join and feeling 
certain that these have been fully vetted.
    That is my concern in this space and why I wanted to raise 
it. I want to say again thank you to Senator Braun for holding 
this hearing. I look forward to continuing to fight alongside 
you for patients with rare and progressive diseases. We need to 
do better in this space. Thank you.
    The Chairman. Thank you, Senator Warren. Senator Vance.
    Senator Vance. Thank you, Mr. Chairman, and I am going to 
direct my questions to Mr. Desserich, so first, let me just 
say, you know, I have got a six-year old, a three-year old, and 
a one-year old, and my heart goes out to you because I know 
that you have engaged in this fight because you lost a seven-
year old daughter.
    I know a lot of other folks here who have lost kids, and my 
heart goes out to you as well. The goal here, of course, is to 
try to get to a society where no parent has to bury their own 
kid because of an illness that is currently incurable. I know 
we are all working toward that goal, and the worry that I have 
is that given the limited patient populations, because some of 
these diseases are incredibly rare, and because of how 
differently we treat pediatric illnesses and the medicines to 
treat pediatric illnesses, that we are making some mistakes 
here.
    I know, Mr. Desserich, there is an argument that the Right 
to Try legislation, the expanded access that happened during 
the last Administration, which I think was a good thing, that 
that satisfies some of the concerns that you have with the 
current way in which we give patients access to these drugs.
    I would like you maybe just to explain why that is not 
right. What are we still not doing correctly in this space?
    Mr. Desserich. Well, I think any time that we have tried 
any of the Right to Try elements within our specific disease 
classification, there has been a unwillingness to make it apply 
to pediatrics.
    You know, Right to Try seems to be something that may have 
some adult applications to it, and I can't really speak to it 
because I don't touch those populations, but within the 
pediatric realm with it, everybody has kind of looked at it and 
said, well, yes, it is not going to go for children's cancers.
    I think that is--you know, that is really the cornerstone 
of everything that we are talking about here is because I think 
what we

[[Page 27]]

tend to do is we tend to think it along the lines of the ideal 
circumstance.
    We think of it as a clinical trial, and how these can be 
perfected, and how we can do better with it, but at the end of 
the day, you know, all these acts and all these regulations are 
dealing with imperfect scenarios. You know, a clinical trial 
requires things such as investment accrual, time, biomarkers, 
and certainly a completion, and the issue is, while we all, I 
think, see the need for clinical trials, we are dealing with 
scenarios to which these things don't exist.
    We can't get it. You know, we can't get accruals. I mean, I 
am witnessing right now a trial that we are putting out there 
with kids in our disease classification, and they have an 
accrual number of 400 patients.
    We only have 400 kids that are diagnosed per year. That 
means this trial is never going to get finished. It is going to 
have eight years to be able to get there, and by then we are 
already going to know whether it works or doesn't work with it, 
and so, you can't think of it in those ways.
    We have to go into this with the idea that we don't have 
the things to do the clinical trials sometimes, and so, 
Promising Pathway effectively fills that need.
    Senator Vance. Mr. Desserich, can you explain to me just 
this particular point, so very often, and I have worked with 
companies in my private life, my prior life, I should say. When 
I was in the private sector, we actually worked with some 
biopharmaceutical companies doing clinical trials.
    You know, one of the things, of course, you are trying to 
do in some of these cancer therapeutics is identify whether the 
addition of the therapeutic increases the life of the patient, 
right. It is sort of one of the primary endpoints oftentimes.
    In some of the diseases we are dealing with, especially in 
pediatric cases, extending the time from, you know, three 
months of life to nine months of life is not really practical 
because the time given for the individual patient, for a child 
is so small, so the idea that you are going to somehow reach a 
classic adult endpoint in a pediatric case sometimes just 
doesn't make any sense, does it?
    Mr. Desserich. Absolutely not. I mean, we can't reach those 
endpoints. I mean, frankly, I think our community is happy with 
anything that we can add. I mean, just another day is what we 
are looking for.
    Senator Vance. Sure.
    Mr. Desserich. We have seen some things that have worked, 
that we have applied, and we tried to do this with, and, you 
know, they have added months. You know, right now I would guess 
from looking at some of the registry data, we see that we have 
probably expanded that by threefold, and that is good.
    We were only talking about, you know, maybe six months, so 
threefold is a year and a half. That is not a life by any 
stretch of the imagination. Will it ever be at that case? It is 
just we have to take it and we have to try to grow it as much 
as we can.
    Senator Vance. I appreciate that. I appreciate all of you 
for being here, and the last comment I would make here is that 
we all understand that we have to do better.

[[Page 28]]

    What occurs to me, just in looking at the, you know, 
Senator Braun's PPA and just talking with Mr. Desserich both in 
this context and in others, is that we have a clinical trial 
situation, we have a clinical trial infrastructure in this 
country that is in some ways designed for adult diseases and 
very common diseases.
    If we don't fix the underlying infrastructure, we may have 
a lot of kids out there who are languishing, who are dying, not 
because there aren't therapeutics and not because there isn't 
capital to invest in these new therapeutics, but because the 
regulatory regime doesn't allow us to actually try these things 
and figure out whether they work.
    I think we need to fix that problem. I applaud Senator 
Braun for trying to take a swing at it.
    Mr. Desserich. If I may add something to that as well. The 
other thing I think that we also miss is that for the most 
part, we view our kids as not the same level as an adult case, 
and so, what we do is we tend to say, let's take a drug that we 
know works in some other cancer and let's give it a try in 
kids, and for that we can do clinical trials. For those, we can 
put them out there, but what happens most often, especially 
right now, with all the knowledge and all the investment that 
we put into this, and the registries, and the tracking, and the 
patterns, and everything we have been able to find, for the 
first time we have an ability to craft a drug that focuses on 
DIPG.
    I can't get it out. I can't get it to a bedside because I 
can't put it in adults. Adults don't normally get this, so we 
are at a stop point. You know, my reference to you and the 
reason for bringing these 46 grants is to impress upon you how 
important it is, because I can't--I don't think I can get a lot 
of these into a clinical trial.
    The Chairman. Thank you, Senator Vance. Before turning to 
Senator Warnock, I just want to give a sense of the time 
constraints we are under. Now we have a vote that is opened and 
well underway.
    After Senator Warnock, I will turn to Senator Braun, and 
then I might have one quick question and then we will have to 
conclude the hearing, but, Senator Warnock.
    Senator Warnock. Thank you very much, Chair Casey and 
Ranking Member Braun, for holding this important hearing today, 
and I am really grateful for your leadership on this issue, 
particularly Ranking Member Braun.
    It is great to work with you on legislation to advance this 
important work. I have heard from Georgians across the State 
who have been personally affected by rare and serious diseases, 
from ALS to Barth syndrome, to many others, and despite the 
differences in these diseases, there is one thing they have in 
common, patients desperately, desperately need improved access 
to treatment, and that is why I was proud to co-sponsor Ranking 
Member Braun's Promising Pathway Act. That is good public 
policy, and it would help patients with life threatening 
diseases receive early access to promising treatments.
    Mr. Desserich, how would the Promising Pathway Act improve 
access to lifesaving treatments for patients who have serious 
diagnoses? I ask this, you know, recognizing that you have been 
personally impacted by this, even as you remember your own 
daughter.

[[Page 29]]

    Let me thank you for translating your pain and the power 
and being such an important voice on this, and so, from your 
experience, how would the Promising Pathway Act help?
    Mr. Desserich. I think in our case with it, it is a 
question of time and direction toward pediatrics. I think, you 
know, everybody looks at this, at the Promising Pathway Act, as 
an ability to be able to, you know, find something that, you 
know, generally satisfies the safety requirements and we can 
try to move it toward, you know, giving it a conditional 
approval.
    We are certainly moving that up and I think that helps any 
patient in a terminal diagnosis. With regards to the pediatrics 
side of things, what Promising Pathways does that I think 
better than others is it allows it to move faster into the 
pediatric realm by--especially in those rare and terminal 
cases.
    Now, that is not all cases. You know, there is also some 
specific definitions of what is a terminal case in this that I 
think really help to, you know, provide some clarity to it, but 
you know, short of that, we can't get it there. You know, we 
can't get these trials into the pediatric realm with it.
    We need a perfect, ideal scenario and the cancers that we 
are dealing with are absolutely nothing close to ideal. You 
know, they--it changes everything.
    Senator Warnock. It is also important that we include 
patient perspective and priorities into our therapy 
development. Professor Fernandez Lynch, can you discuss some of 
the advances that the patient focused drug development program 
have provided?
    Mrs. Fernandez Lynch. Of course. Thank you for the 
question, Senator Warnock. FDA has a formal program called 
Patient Focused Drug Development, and it is worth acknowledging 
the major strides the agency has made over the past several 
decades, starting with the HIV/AIDS advocacy, pushed to help 
FDA recognize that patients deserve a seat at the table.
    Patient focused drug development really refers to a 
systematic approach to ensuring that patients' experiences, 
perspectives, needs, and priorities are captured and 
meaningfully incorporated into both drug development and FDA's 
evaluation of drugs, because it recognizes that patients have 
expertise in the diseases that they are facing.
    It is important to hear from patients and FDA has stated 
that it needs to hear from patients about clinical trial design 
and what are the end points that are meaningful to them. What 
are the things that should be measured in trials? What makes 
clinical trials feasible to participate in?
    Senator Warnock. Do you--and I hate to interrupt, but I am 
going to be out of time in a little bit. Do you have example of 
advances made by the program that you could share?
    Mrs. Fernandez Lynch. I can--what I can share with you are 
the types of activities that FDA has engaged in, which are a 
variety of guidance documents to help companies understand how 
to systematically collect information from patients that will 
be meaningful, and they also have a program to develop clinical 
outcome assessments, which are also intended to be specific 
endpoints that are meaningful to patients, and then in addition 
to the patient focused drug development program, there has been 
further incorpora

[[Page 30]]

tion of patient voices as representatives on advisory 
committees to FDA.
    Senator Warnock. Thank you. Patients voices are critical to 
this process and thank you for your leadership. Thank you, Mr. 
Chair.
    The Chairman. Thank you, Senator Warnock. I will turn to 
Ranking Member Braun.
    Senator Braun. Thank you, Mr. Chairman. Before my last 
question, Senator Murkowski from Alaska wants to enter into 
the--Senator Murkowski from Alaska wants to enter into the 
record by unanimous consent support for the Promising Pathways 
Act.
    The Chairman. Without objection.
    Senator Braun. Last question. Dr. Bhatnagar, so often you 
hear folks have to leave the country to get leading edge 
treatment. That is a shame. We should be that leading edge and 
we should have a system that accommodates it.
    Could you talk about the difference between our system and 
one that seems to be working better, which would be in Europe 
in terms of how they have done provisional approval, and please 
comment on that because if that is better, we should at least 
be emulating that.
    Dr. Bhatnagar. Thank you, Senator. It is a good question, 
and I think it is debatable which one is better. I think it is 
true that there are certain therapies where access is more 
elsewhere.
    I think our regulators are clearly top notch. The world 
looks up to the FDA for what they are going to do, but I think 
there are times when there are delays which are unnecessary. 
There are situations such as approving drugs early in the 
process where we don't have the same considerations.
    Just very quickly, because I know we are almost out of 
time, the accelerated approval pathway as it exists in the U.S. 
really is focused on two constructs. One is you have a known 
biomarker or a surrogate that predicts benefit, and the second 
is an intermediate clinical benefit that predicts ultimate use.
    The challenge with both of these is that neither of them is 
really present in most rare disease situations. Last year, CEDR 
approved 37 drugs. Six were accelerated. Five of them were 
oncology drugs. One was a nonmalignant hematology drug. The 
point is that oncology is an area where these diseases are 
really well understood.
    Other rare diseases, we cannot use the pathways. Europe has 
prospectively defined certain things that they can do on a 
regulatory side. You can negotiate a study design with the 
regulators prior to approval and get an approval in that 
manner. We don't have the same provisions.
    Senator Braun. Thank you.
    The Chairman. Thank you, Ranking Member Braun. I just have 
one more question. I know we have to wrap up. Professor 
Fernandez Lynch, in your testimony, you stated the following, 
``it is certainly understandable for individual patients to be 
willing to risk substantial uncertainty for themselves before 
better evidence becomes available, especially when they have no 
time to lose, and I support their right to do so via expanded 
access. However, weakened approval standards affect all 
patients.''
    Could you talk about this balance that I know we all want 
to strike from an ethical perspective, the balance between the 
needs

[[Page 31]]

of the patients when not all patients have the same needs or 
the same level of risk tolerance.
    Mrs. Fernandez Lynch. Yes, of course. Thank you for the 
question. One of the things that I have often heard in the 
context of discussing Promising Pathways is if patients don't 
want to take a provisionally approved drug, then of course they 
don't have to.
    That is absolutely true, but it becomes more complicated 
because when you lower FDA approval standards, that tells 
industry, this is the bar that you have to meet. When that bar 
is lowered, then industry responds accordingly.
    What that does is push back to patients and clinicians the 
need to make decisions without evidence. Now, some people may 
have that high risk tolerance, but not everybody will, and that 
is why I think the dietary supplement example is so salient.
    Dietary supplements do not have to show safety and 
effectiveness, and so industry does not demonstrate that. That 
is not what people who are facing these terrible diseases need. 
The other challenge is when the standards are low and you allow 
products on the market that have not demonstrated that they are 
beneficial, it complicates the development of potentially 
better drugs because it makes it difficult to accrue those 
studies and then you might also find yourself having to test 
new interventions against interventions that have not yet been 
proven to work.
    You can't quite tell, are patients benefiting from this new 
drug, or is it that neither of these drugs are beneficial? So, 
you can entrench drugs that don't actually benefit patients.
    FDA has to account in its public health responsibilities 
not only for the interests of patients today, but also the 
broader population of patients, which is why I am encouraging 
the Committee to draw on what we have heard about challenges to 
the expanded access pathway.
    I think that is the avenue that really does need to be 
improved and provides this balance, allowing patients today who 
have high risk tolerance to take unproven medicines while we 
continue to gather rigorous evidence.
    Unfortunately, patient registries are not going to get us 
there because they are not randomized, not controlled. They are 
not going to be able to answer these questions in the way that 
patients need to make autonomous, informed decisions about 
their treatment.
    The Chairman. Thank you, everyone. We are going to turn to 
our closing statements, and I will turn to Ranking Member 
Braun, and if he has to leave before mine is completed, I won't 
be offended.
    Senator Braun. Thank you, Mr. Chairman. I have been working 
on this for most of the five-years I have been here in the 
Senate, and I come from a world where I was in the logistics 
and distribution business, and it is frustrating sometimes when 
you want to get from here to there.
    I think we have had a really good discussion with it today, 
and we have heard most importantly from folks that are 
suffering through it, and I think if there is one lesson to 
learn, we need to have more of that even on other diseases. 
Here the urgency is even more compelling.
    This is a bipartisan effort. After much work, I think it is 
going to cascade into something quicker than what most bills 
take since

[[Page 32]]

it took so long to get here. In the face of such cruel 
diseases, a more compassionate and flexible path has got to be 
there for patients. Why does Europe have such a pathway and we 
do not?
    I look forward to working with my colleagues to speed up 
access for individuals with these diseases while maintaining 
the gold standard of the FDA. We can do both at once. This is 
not a Republican or Democrat discussion. This is a human 
discussion.
    We all have stories that are deeply personal, seeing 
firsthand the impact of how these diseases ravage not only the 
victims, the families as well. It is time for us to turn the 
passion into action, and we are going to do so. Thank you, Mr. 
Chair.
    The Chairman. Ranking Member Braun, thank you very much. As 
we have all heard today from patients and from family members 
who are desperately awaiting hope, awaiting a treatment, we 
have also heard today from patients who have lived their whole 
lives without any therapies for their condition.
    We have heard about--from the caregiver perspective, 
spouses, family members, a father who lost a daughter, hearing 
how hard it is to watch a family member suffer with no 
treatment options. We have also heard about the challenges that 
the drug companies face when working to bring a drug for a rare 
disease to market.
    We have heard about how to balance the unique challenges 
posed by rare diseases with regulatory processes that uphold, 
as Senator Braun said, the FDA's gold standard. We must 
continue the discussion with each other in the Senate, with the 
FDA, and all that have a stake in this, all the families who 
are represented here today.
    We have got to substantially, substantially improve the 
process for getting new drugs to patients while maintaining 
standards of efficacy and safety, so I want to thank all the 
witnesses today for their contributions, for the time they 
spent here, and for sharing very personal details about your 
lives. That is not easy to do in a public setting.
    For the record, if any Senators have additional questions 
for the witnesses or statements to be added, the hearing record 
will be kept open for seven days until next Thursday, November 
the 2nd. Thank you all for participating in this hearing. This 
concludes our hearing.
    [Whereupon, at 11:57 a.m., the hearing was adjourned.]


     
      
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                       Statements for the Record

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