[House Hearing, 117 Congress]
[From the U.S. Government Publishing Office]
THE FUTURE OF MEDICINE: LEGISLATION TO
ENCOURAGE INNOVATION AND IMPROVE OVER-
SIGHT
=======================================================================
HYBRID HEARING
BEFORE THE
SUBCOMMITTEE ON HEALTH
OF THE
COMMITTEE ON ENERGY AND COMMERCE
HOUSE OF REPRESENTATIVES
ONE HUNDRED SEVENTEENTH CONGRESS
SECOND SESSION
__________
MARCH 17, 2022
__________
Serial No. 117-75
[GRAPHIC NOT AVAILABLE IN TIFF FORMAT]
Published for the use of the Committee on Energy and Commerce
govinfo.gov/committee/house-energy
energycommerce.house.gov
__________
U.S. GOVERNMENT PUBLISHING OFFICE
59-698 PDF WASHINGTON : 2026
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COMMITTEE ON ENERGY AND COMMERCE
FRANK PALLONE, Jr., New Jersey
Chairman
BOBBY L. RUSH, Illinois CATHY McMORRIS RODGERS, Washington
ANNA G. ESHOO, California Ranking Member
DIANA DeGETTE, Colorado FRED UPTON, Michigan
MIKE DOYLE, Pennsylvania MICHAEL C. BURGESS, Texas
JAN SCHAKOWSKY, Illinois STEVE SCALISE, Louisiana
G. K. BUTTERFIELD, North Carolina ROBERT E. LATTA, Ohio
DORIS O. MATSUI, California BRETT GUTHRIE, Kentucky
KATHY CASTOR, Florida DAVID B. McKINLEY, West Virginia
JOHN P. SARBANES, Maryland ADAM KINZINGER, Illinois
JERRY McNERNEY, California H. MORGAN GRIFFITH, Virginia
PETER WELCH, Vermont GUS M. BILIRAKIS, Florida
PAUL TONKO, New York BILL JOHNSON, Ohio
YVETTE D. CLARKE, New York BILLY LONG, Missouri
KURT SCHRADER, Oregon LARRY BUCSHON, Indiana
TONY CARDENAS, California MARKWAYNE MULLIN, Oklahoma
RAUL RUIZ, California RICHARD HUDSON, North Carolina
SCOTT H. PETERS, California TIM WALBERG, Michigan
DEBBIE DINGELL, Michigan EARL L. ``BUDDY'' CARTER, Georgia
MARC A. VEASEY, Texas JEFF DUNCAN, South Carolina
ANN M. KUSTER, New Hampshire GARY J. PALMER, Alabama
ROBIN L. KELLY, Illinois, Vice NEAL P. DUNN, Florida
Chair JOHN R. CURTIS, Utah
NANETTE DIAZ BARRAGAN, California DEBBIE LESKO, Arizona
A. DONALD McEACHIN, Virginia GREG PENCE, Indiana
LISA BLUNT ROCHESTER, Delaware DAN CRENSHAW, Texas
DARREN SOTO, Florida JOHN JOYCE, Pennsylvania
TOM O'HALLERAN, Arizona KELLY ARMSTRONG, North Dakota
KATHLEEN M. RICE, New York
ANGIE CRAIG, Minnesota
KIM SCHRIER, Washington
LORI TRAHAN, Massachusetts
LIZZIE FLETCHER, Texas
------
Professional Staff
TIFFANY GUARASCIO, Staff Director
WAVERLY GORDON, Deputy Staff Director
NATE HODSON, Minority Staff Director
Subcommittee on Health
ANNA G. ESHOO, California
Chairwoman
G. K. BUTTERFIELD, North Carolina BRETT GUTHRIE, Kentucky
DORIS O. MATSUI, California Ranking Member
KATHY CASTOR, Florida FRED UPTON, Michigan
JOHN P. SARBANES, Maryland, Vice MICHAEL C. BURGESS, Texas
Chair H. MORGAN GRIFFITH, Virginia
PETER WELCH, Vermont GUS M. BILIRAKIS, Florida
KURT SCHRADER, Oregon BILLY LONG, Missouri
TONY CARDENAS, California LARRY BUCSHON, Indiana
RAUL RUIZ, California MARKWAYNE MULLIN, Oklahoma
DEBBIE DINGELL, Michigan RICHARD HUDSON, North Carolina
ANN M. KUSTER, New Hampshire EARL L. ``BUDDY'' CARTER, Georgia
ROBIN L. KELLY, Illinois NEAL P. DUNN, Florida
NANETTE DIAZ BARRAGAN, California JOHN R. CURTIS, Utah
LISA BLUNT ROCHESTER, Delaware DAN CRENSHAW, Texas
ANGIE CRAIG, Minnesota JOHN JOYCE, Pennsylvania
KIM SCHRIER, Washington CATHY McMORRIS RODGERS, Washington
LORI TRAHAN, Massachusetts (ex officio)
LIZZIE FLETCHER, Texas
FRANK PALLONE, Jr., New Jersey (ex
officio)
C O N T E N T S
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Page
Hon. Anna G. Eshoo, a Representative in Congress from the State
of California, opening statement............................... 2
Prepared statement........................................... 4
Hon. Brett Guthrie, a Representative in Congress from the
Commonwealth of Kentucky, opening statement.................... 6
Prepared statement........................................... 8
Hon. Frank Pallone, Jr., a Representative in Congress from the
State of New Jersey, opening statement......................... 12
Prepared statement........................................... 14
Hon. Cathy McMorris Rodgers, a Representative in Congress from
the State of Washington, opening statement..................... 16
Prepared statement........................................... 18
Witnesses
Ruben Mesa, M.D., Executive Director, Mays Cancer Center, UT
Health San Antonio MD Anderson................................. 23
Prepared statement........................................... 25
David Gaugh, Senior Vice President, Sciences and Regulatory
Affairs, Association for Accessible Medicines.................. 29
Prepared statement........................................... 31
Lucy Vereshchagina, Ph.D., Vice President, Science And Regulatory
Advocacy, Pharmaceutical Research and Manufacturers of America. 44
Prepared statement........................................... 46
Answer to submitted questions................................ 282
Cartier Esham, Ph.D., Chief Scientific Officer, Executive Vice
President, Emerging Companies, Biotechnology Innovation
Organization................................................... 50
Prepared statement........................................... 52
Answer to submitted questions................................ 286
Jeff Allen, Ph.D., President and CEO, Friends of Cancer Research. 62
Prepared statement........................................... 64
Answer to submitted questions................................ 290
Reshma Ramachandran, M.D., M.P.P., Chair, Doctors for America FDA
Task Force, Physician-Fellow, Yale National Clinician Scholars
Program, Yale School of Medicine............................... 77
Prepared statement........................................... 79
Answer to submitted questions................................ 294
Submitted Material
H.R. 1730, the Speeding Therapy Access Today Act of 2021,
submitted by Ms. Eshoo\1\
H.R. 2565, the FDA Modernization Act of 2021, submitted by Ms.
Eshoo\1\
H.R. 3085, the Equity in Neuroscience and Alzheimer's Clinical
Trials Act of 2021, submitted by Ms. Eshoo\1\
H.R. 3927, the Manufacturing API, Drugs, and Excipients in
America Act, submitted by Ms. Eshoo\1\
H.R. 4472, the Better Empowerment Now to Enhance Framework and
Improve Treatments Act of 2021, submitted by Ms. Eshoo\1\
H.R. 4511, the FDA Advancing Collection of Transformative Science
Act, submitted by Ms. Eshoo\1\
H.R. 5030, the Diversifying Investigations Via Equitable Research
Studies for Everyone Trials Act, submitted by Ms. Eshoo\1\
H.R. 5566, the Finding Orphan-disease Remedies With Antifungal
Research and Development Act of 2021, submitted by Ms. Eshoo\1\
H.R. 5585, the Advanced Research Project Agency-Health Act,
submitted by Ms. Eshoo\1\
H.R. 6000, the Cures 2.0 Act, submitted by Ms. Eshoo\1\
H.R. 6963, the Accelerated Approval Integrity Act of 2022,
submitted by Ms. Eshoo\1\
H.R. 6972, the Give Kids a Chance Act, submitted by Ms. Eshoo\1\
H.R. 6973, the Enhanced Access to Affordable Medicines Act,
submitted by Ms. Eshoo\1\
H.R. 6988, the Drug Manufacturing Innovation Act, submitted by
Ms. Eshoo\1\
H.R. 6996, the Accelerating Access for Patients Act, submitted by
Ms. Eshoo\1\
H.R. 7006, the Improving the Nation's Safe Pharmaceuticals and
Excipients by Creating Tools for Inspecting and Overseeing
Needed Supplies Act, submitted by Ms. Eshoo\1\
H.R. 7008, the Pre-Approval Information Exchange Act, submitted
by Ms. Eshoo\1\
H.R. 7032, the Increasing Transparency in Generic Drug
Applications Act, submitted by Ms. Eshoo\1\
H.R. 7035, the Biologics Market Transparency Act, submitted by
Ms. Eshoo\1\
H.R. 7047, A bill to amend title III of the Public Health Service
Act with respect to the determination by the Secretary
regarding certain biosimilar application elements, and for
other purposes, submitted by Ms. Eshoo\1\
Letter of March 16, 2022, from Vern Buchanan, Member of Congress,
to Ms. Eshoo and Mr. Guthrie, submitted by Ms. Eshoo........... 149
Letter of March 16, 2022, from Jeffrey Brown, Science Advisor,
People for the Ethical Treatment of Animals, to Ms. Eshoo, et
al., submitted by Ms. Eshoo.................................... 151
Statement of March 17, 2022, National Organization for Rare
Disorders, submitted by Ms. Eshoo.............................. 153
Statement to Ms. Eshoo and Mr. Guthrie, submitted by Ms. Eshoo... 159
Letter of February 25, 2022, from Molly Guthrie, Senior Director
of Public Policy and Advocacy, Susan G. Komen, to Ms. Eshoo, et
al., submitted by Ms. Eshoo.................................... 160
Letter of March 16, 2022, from Orly Avitzur, MD, MBA, FAAN,
President, American Academy of Neurology, to Ms. Eshoo and Mr.
Guthrie, submitted by Ms. Eshoo................................ 162
Letter of March 17, 2022, from Sophia McLeod, Director of
Government Relations, Association of Clinical Research
Organizations, to Ms. Eshoo and Mr. Guthrie, submitted by Ms.
Eshoo.......................................................... 166
Letter of March 16, 2022, to Ms. Murray, et al., from Pediatric
Cancer Advocacy Organizations, submitted by Ms. Eshoo.......... 170
Letter of March 17, 2022, from Andrea Noda, Vice President of
Health Care, Arnold Ventures to Mr. Pallone and Mrs. McMorris
Rodgers, submitted by Ms. Eshoo................................ 174
Statement of March 17, 2022, from Howard ``Skip'' Burris,
President, Association for Clinical Oncology, submitted by Ms.
Eshoo.......................................................... 178
----------
\1\ The legislation has been retained in committee files and is
available at https://docs.house.gov/Committee/Calendar/
ByEvent.aspx?EventID=114510.
Testimony from Wayne Pacelle and Tamara Drake, the Center for a
Humane Economy, Animal Wellness Action, Animal Foundation, and
SPCA International \2\
Article ``A Community Vision for a Rare Center of Excellence at
the FDA,'' from EveryLife Foundation, submitted by Ms. Eshoo
\3\
Article of March 16, 2022, ``Congress Needs to Fix the FDA's
`Accelerated' Drug-Approval Process,'' by Lisa Jarvis,
Bloomberg, submitted by Ms. Eshoo.............................. 184
Letter of March 17, 2022, from the leading pediatric cancer
clinical and preclinical, to Ms. Murray, et al., submitted by
Ms. Eshoo...................................................... 189
Statement of March 17, 2022, from Matthew Rizzo, Chair, American
Brain Coalition, submitted by Ms. Eshoo........................ 190
Statement of March 17, 2022, from the EveryLife Foundation for
Rare Diseases, submitted by Ms. Eshoo.......................... 193
Testimony of March 17, 2022, from Jim Corbett, CEO, Emulate,
Inc., submitted by Ms. Eshoo................................... 198
Letter of March 16, 2022, from Robert Egge, Chief Public Policy
Officer, Alzheimer's Association, Executive Vice President,
Alzheimer's Impact Movement and Cynthia Rice, Chief Mission
Strategy Officer, JDRF, submitted by Ms. Eshoo................. 202
Letter of October 20, 2021, from Stakeholders, to Ms. Eshoo,
submitted by Ms. Eshoo......................................... 204
Letter of March 15, 2022, from Nancy D. Ginter, Director of
Administration, Beyond Celiac, to Ms. Eshoo and Mr. Guthrie,
submitted by Ms. Eshoo......................................... 205
Letter of March 15, 2022, from Scout, Ph.D., Executive Director,
National LGBT Cancer Network, to Ms. Eshoo and Mr. Guthrie,
submitted by Ms. Eshoo......................................... 206
Letter of March 15, 2022, from Abgenics Life Sciences Pvt, Ltd.,
et al., to Members of Congress and Health Legislative Staff,
submitted by Ms. Eshoo......................................... 208
Letter of March 16, 2022, from Royce H. Johnson, M.D., F.A.C.P.,
F.I.D.S.A., and David Geffen School of Medicine at UCLA, Chief,
Infectious Disease, Kern Medical, Medical Director, Valley
Fever Institute, submitted by Ms. Eshoo........................ 212
Statement of March 17, 2022, from Generation Patient, submitted
by Ms. Eshoo................................................... 214
Statement of March 17, 2022, from the Generics Access Project,
submitted by Ms. Eshoo......................................... 218
Letter of March 17, 2021, from Brian Lindberg, Chief Policy
Officer, Chief Legal Officer and General Counsel, National
Marrow Donor Program, the National Marrow Donor Program/Be The
Match, to Mr. Pallone and Mrs. McMorriss Rodgers, submitted by
Ms. Eshoo...................................................... 221
Statement of March 17, 2022, from the Humane Society and Humane
Society Legislative Fund....................................... 224
Letter of May 19, 2021, to Ms. Murray, et al., from EveryLife
Foundation, submitted by Ms. Eshoo............................. 226
Testimony of March 17, 2022, from Dr. Paul A. Locke, Associate
Professor, Johns Hopkins Bloomberg School of Public Health,
Department of Environmental Health and Engineering, submitted
by Ms. Eshoo................................................... 231
Letter of March 17, 2022, from Rep. Kevin McCarthy, Member of
Congress, to Mr. McCarthy, et al., submitted by Ms. Eshoo...... 234
Letter of March 17, 2022, from Dr. Gary Michelson, Founder and
Co-Chair, Michelson Center for Public Policy, to Ms. Eshoo and
et al., submitted by Ms. Eshoo................................. 239
----------
\2\ The information has been retained in committee files and also
is available at https://docs.house.gov/meetings/IF/IF14/
20220317/114510/HHRG-117-IF14-20220317-SD013.pdf.
\3\ The information has been retained in committee files and also
is available at https://docs.house.gov/meetings/IF/IF14/
20220317/114510/HHRG-117-IF14-20220317-SD014.pdf.
Letter of March 16, 2022, to Ms. Eshoo and Mr. Guthrie, from
National Brain Tumor Society, submitted by Ms. Eshoo........... 243
Testimony of March 17, 2022, from Dr. Trivia Frazier, President,
CEO, Obatala Sciences, submitted by Ms. Eshoo.................. 248
Letter of March 16, 2022, Mallika Vastare, Vice President,
Government Affairs, Personal Care Products Council, Tracie
Letterman, Vice President of Federal Affairs, Humane Society
Legislative Fund, and Katie Conlee, Vice President of Animal
Research Issues, Humane Society of the United States, to Mr.
Pallone and Ms. McMorris Rodgers, submitted by Ms. Eshoo....... 250
Letter of March 17, 2022, from Rajarshi Banerjee, CEO,
Perspectum, to Ms. Eshoo, et al., submitted by Ms. Eshoo....... 251
Statement of March 17, 2022, from Kristie Sullivan, Vice
President, Physicians Committee for Responsible Medicine,
submitted by Ms. Eshoo......................................... 260
Letter of March 17, 2022, from 14 stakeholder groups, to Mr.
Pallone and Ms. McMorris Rodgers, submitted by Ms. Eshoo....... 264
Letter of March 17, 2022, from Dr. Hope R. Ferdowsian, President
and CEO, Phoenix Zones Initiative, to Ms. Eshoo and Mr.
Guthrie, submitted by Ms. Eshoo................................ 266
Letter of March 16, 2022, from Rep. Nancy Mace, Member of
Congress, to Ms. Eshoo and Mr. Guthrie, submitted by Ms. Eshoo. 271
Letter of March 17, 2022, from Tabitha Orth, President,
International Autoimmune Encephalitis Society, to Ms. Eshoo and
Mr. Guthrie, submitted by Ms. Eshoo............................ 273
Letter of March 17, 2022, from Dr. J. Lowry Curley, Co-Founder
and CEO, AxoSim Inc., to Ms. Eshoo and Mr. Guthrie, submitted
by Ms. Eshoo................................................... 274
Letter of March 17, 2022, to Ms. Eshoo and Mr. Guthrie, from
Neuroscience Working Table, submitted by Ms. Eshoo............. 276
Letter of March 17, 2022, from Tonya A. Winders, President and
CEO Allergy and Asthma Network, to Ms. Eshoo and Mr. Guthrie,
submitted by Ms. Eshoo......................................... 279
Letter of March 17, 2022, from Ada D. Stewart, MD, FAAFP, Board
Chair, American Academy of Family Physicians, to Ms. Eshoo and
Mr. Guthrie, submitted by Ms. Eshoo............................ 280
THE FUTURE OF MEDICINE: LEGISLATION TO ENCOURAGE INNOVATION AND IMPROVE
OVERSIGHT
----------
THURSDAY, MARCH 17, 2022
House of Representatives,
Subcommittee on Health,
Committee on Energy and Commerce,
Washington, DC.
The subcommittee met, pursuant to notice, at 10:34 a.m. in
the John D. Dingell Room, 2123 of the Rayburn House Office
Building, and remotely via Cisco Webex online video
conferencing, Hon. Anna Eshoo (chairwoman of the subcommittee),
presiding.
Members present: Representatives Eshoo, Butterfield,
Matsui, Castor, Sarbanes, Welch, Schrader, Cardenas, Ruiz,
Dingell, Kuster, Kelly, Barragan, Blunt Rochester, Craig,
Schrier, Trahan, Fletcher, Pallone (ex officio); Guthrie
(subcommittee ranking member), Upton, Griffith, Bilirakis,
Long, Bucshon, Hudson, Carter, Dunn, Curtis, Crenshaw, Joyce,
and Rodgers (ex officio).
Also present: Representatives DeGette and Tonko
Staff present: Lydia Abma, Fellow; Vincent Amatrudo, FDA
Detailee; Jacquelyn Bolen, Health Counsel; Waverly Gordon,
Deputy Staff Director and General Counsel; Tiffany Guarascio,
Staff Director; Stephen Holland, Senior Health Counsel; Zach
Kahan, Deputy Director Outreach and Member Service; Mackenzie
Kuhl, Press Assistant; Una Lee, Chief Health Counsel; Aisling
McDonough, Policy Coordinator; Meghan Mullon, Policy Analyst;
Juan Negrete, Junior Professional Staff Member; Kaitlyn Peel,
Digital Director; Caroline Rinker, Press Assistant; Chloe
Rodriguez, Clerk; Kylea Rogers, Staff Assistant; Andrew
Souvall, Director of Communications, Outreach, and Member
Services; Charlton Wilson, Fellow; Caroline Wood, Staff
Assistant; C.J. Young, Deputy Communications Director; Hilary
Carruthers, Fellow; Alec Aramanda, Minority Professional Staff
Member, Health; Kate Arey, Minority Content Manager and Digital
Assistant; Sarah Burke, Minority Deputy Staff Director; Grace
Graham, Minority Chief Counsel, Health; Nate Hodson, Minority
Staff Director; Peter Kielty, Minority General Counsel; Bijan
Koohmaraie, Minority Chief Counsel, Oversight and
Investigations Chief Counsel; Clare Paoletta, Minority Policy
Analyst, Health; Kristin Seum, Minority Counsel, Health;
Kristen Shatynski, Minority Professional Staff Member, Health;
and Olivia Shields, Minority Communications Director.
Ms. Eshoo. The Subcommittee on Health will now come to
order.
And due to COVID-19, today's hearing is being held
remotely, as well as in person.
In accordance with the updated guidance issued by the
attending physician, members, staff, and members of the press
present in the hearing room are not required to wear a mask. So
we are moving along in the right direction.
For members and witnesses taking part remotely, microphones
will be set on mute to eliminate background noise. Members and
witnesses will need to unmute their microphones when you wish
to speak.
Since members are participating from different locations at
today's hearing, recognition of members for questions will be
in the order of subcommittee seniority.
And documents for the record should be sent to Meghan
Mullon at the email address we have provided to staff. All
documents will be entered into the record at the conclusion of
the hearing.
The Chair now recognizes herself for 5 minutes for an
opening statement.
OPENING STATEMENT OF HON. ANNA G. ESHOO, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF CALIFORNIA
Today our subcommittee examines 22--everybody hear that
right--22 mostly bipartisan bills to speed the discovery of
more cures, improve patient representation in clinical trials,
and enhance the FDA's ability to fulfill its vital mission of
ensuring the safety, efficacy, and quality of America's drug
supply. This hearing is an enormous legislative undertaking,
and I appreciate the very, very thoughtful work of so many
subcommittee members in putting these bills forward.
First we are examining a bill I introduced, H.R. 5585, the
Advanced Research Project Agency for Health Act. This
legislation would establish ARPA-H as an independent agency
within HHS, with a Presidentially appointed director who would
have the authority to approve and terminate project funding,
establish milestones, and coordinate with other health
agencies, including NIH.
ARPA-H will embody the nimble spirit of the highly regarded
and successful Defense Advanced Research Project Agency--we use
the shorthand, DARPA--to pursue large-scale, high-risk
projects. It will break the mold for Federal research agencies
by being uniquely focused on solving the valley of death to
deliver transformational cures. ARPA-H will correct the gap
that currently exists between the basic research pursued by the
NIH, and the development of commercial products by the private
sector.
With this mission, ARPA-H will drive scientific
breakthroughs to improve our Nation's health, and help fulfill
the President's promise to end cancer as we know it. On Tuesday
the President signed into law the bipartisan Consolidated
Appropriations Act of 2022, which provided $1 billion--that is
with a B--to establish an independent ARPA-H within HHS. This
is a momentous first step in creating an agency that will be a
beacon of hope for the American people.
But our work isn't done yet. Our committee needs to pass
the ARPA-H legislation to provide the agency with the full
authorities it needs to be successful from day one, including
ensuring that it will be a nimble, dynamic, and independent
agency.
Complementing ARPA-H is Representatives Upton and DeGette's
Cures 2.0 legislation that they have been working on for three
years. It ensures that our Federal public health agencies are
working seamlessly together to move new cures through the
research stage all the way to FDA approval and Medicare
coverage. We have great confidence in what Representatives
Upton and DeGette produced in Cures 1.0, so that imprimatur on
that legislation and how well it has worked, I think, is
foundational in terms of not only their approach, but the
confidence that we have in the legislation that they have
produced.
Next we are considering three bills to improve the
diversity of patients enrolling in clinical trials. All
Americans should be confident that their treatments will work
for them regardless of race, of gender, or age. But FDA data
shows that, for the drugs approved in 2020, 75 percent of
clinical trial participants were White. Only eight percent of
trial participants were African American, 11 percent were
Hispanic.
My legislation, the DEPICT Act, would have drug companies
demonstrate how they will include diverse populations in their
clinical trials by reporting to FDA a diversity action plan
with targets by demographic subgroups. It would also give FDA
the ability to ask for a post-market study to gather more data
if a sponsor does not meet the demographic targets it sets for
itself.
Representative Blunt Rochester's ENACT Act and
Representative Ruiz's Diverse Trials Act complement the DEPICT
Act by addressing the barriers and the burdens that often keep
patients from being able to enroll in clinical trials.
Finally, but not least, certainly, Chairman Pallone and
Ranking Member McMorris Rodgers have each proposed changes to
the FDA's accelerated approval program, while several other
members have proposed bills to streamline the development and
approval processes for drugs, especially for rare diseases and
pediatric cancers.
So colleagues, we have a brilliant panel of industry and
physician experts to advise us on these bills, as many of them
previously--during our previous hearing on the FDA drug user
fee agreements. And we all look forward to a highly instructive
hearing on these important bills.
[The prepared statement of Ms. Eshoo follows:]
Prepared Statement of Hon. Anna Eshoo
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Ms. Eshoo. The Chair now recognizes the distinguished
ranking member of the Subcommittee on Health for 5 minutes for
his opening statement Mr. Guthrie.
OPENING STATEMENT OF HON. BRETT GUTHRIE, A REPRESENTATIVE IN
CONGRESS FROM THE COMMONWEALTH STATE OF KENTUCKY
Mr. Guthrie. Thank you, Madam Chair. I really appreciate
this hearing. And I didn't realize that right before the
hearing starts the Zoom goes live, and so I think last time I
was--I didn't realize that until I read in The Hill in Hits and
Misses that what I said was live. And I said last time--I think
I told you I had the most boring opening statement that I have
probably ever given ready for the last time around.
[Laughter.]
Mr. Guthrie. And what I will tell is, listening to me read
through a list of bills is probably not exciting. I admit that.
I can readily admit that.
But what we are doing is exciting, and it is consequential.
It is very interesting, and it is--what we are--the title of
the thing, ``Encourage Innovation,'' and innovation going on in
the pharmaceutical space, innovation going in the medical
device space. The information that is going on in healthcare in
this country is consequential, and exciting to me. So hearing
me talk about it may not be, but I want to definitely say that
what you guys are doing and what our country is doing is
absolutely important and changing people's lives.
So as we begin this hearing, this is a far more exciting
opening statement, because we are here today to discuss
proposals designed to increase American biopharmaceutical
innovation, a goal I think we confidently all say we share. And
over the past decade more novel therapies have been approved in
the United States than any other country.
The United States is home to the world's leading
biopharmaceutical industry, with the Food and Drug
Administration approving 50 new therapies in 2017: 27 of the
approved therapies were first-in-class drugs; 26 were to treat
rare diseases. Of these 50 newly approved drugs, 76 percent
were approved in the United States before any other country.
One of the most publicly reported approvals was Biogen's
Aduhelm, through the accelerated approval pathway. This was the
first FDA-approved drug to treat Alzheimer's disease since
2003. It is estimated this historic approval would benefit
nearly one million out of six million Americans living with
early onset Alzheimer's, which now have some hope of treatment
against this vicious disease. Approval of this new Alzheimer's
treatment through accelerated approval pathway could lead to
other potential benefits, including the development of more
effective treatments and encouraging investments in finding a
cure for this terrible disease.
Despite its real promise, the Centers for Medicare and
Medicaid Services is now attempting to only allow access to the
approved drug to a very limited patient population. As CMS
moves forward with this plan, access to Aduhelm and future FDA-
approved Alzheimer's disease treatments would be restricted for
Americans with intellectual disabilities, such as Down's
Syndrome, and patients with other neurological conditions. This
could have a chilling effect on investment in Alzheimer's
research moving forward.
Not only is CMS undermining the accelerated approval
pathway, but we also have a bill before us today that calls for
further restricting the accelerated approval pathway. Instead
of adding more red tape, we should be focused on developing
policy solutions that are intended to break down regulatory
barriers and promote more collaboration between the regulatory
community and the private sector, as I am sure we will as these
bills move forward.
And I am thankful that my colleagues have included my
legislation and several other bipartisan bills in this hearing.
My legislation, H.R. 7008, the Pre-Approval Information
Exchange Act, would help address what is known as the valley of
death, or the time between when a drug or device is approved by
the FDA and when it is covered by a payer.
The bill would specifically allow drug and device sponsors
to share key healthcare economic information, including pre-
clinical trial results and other important information, with
health insurers and other payers before a drug or device is
approved by the FDA. This should help patients gain access to
potentially lifesaving treatments such as Aduhelm more quickly
by giving the marketplace a chance to price in therapies
working toward FDA approval.
In fact, the FDA even acknowledged the potential impact
these communications could have by releasing guidance in 2018
allowing these communications to occur. Codifying this guidance
will instill further confidence in the marketplace, and provide
needed regulatory certainty to the companies and payers already
engaged in these information exchanges.
I encourage my colleagues to support H.R. 7008, which has
broad industry support.
Additionally, in the case of Aduhelm, we should also be
promoting policies that will help ensure patients are receiving
timely access to breakthrough therapies without significantly
increasing the cost of care for our healthcare system.
For example, Representatives Schrader, Mullin, and I have
been working on a bipartisan proposal that would permit State
Medicaid programs to enter into value-based purchasing
agreements. These payment models would have dual benefits. This
could promote greater access to some of the most expensive
treatments on the marketplace for lower-income populations,
while also helping shield State budgets against having to pay
for a drug if it fails to meet its clinical endpoints. This
latter point is especially important when we are talking about
accelerated approvals.
I look forward to continuing to work with the bipartisan
colleagues in advancing this important measure. I also look
forward to finding ways to advance the many proposals we are
discussing today.
[The prepared statement of Mr. Guthrie follows:]
Prepared Statement of Hon. Brett Guthrie
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Mr. Guthrie. And I thank you, and I yield back, Madam
Chair.
Ms. Eshoo. The gentleman--and that is what he is--yields
back. The Chair now is pleased to recognize the chairman of the
full Committee of Energy and Commerce, Mr. Pallone, for your 5
minutes of--for an opening statement.
OPENING STATEMENT OF HON. FRANK PALLONE, Jr., A REPRESENTATIVE
IN CONGRESS FROM THE STATE OF NEW JERSEY
Mr. Pallone. Thank you, Chairwoman Eshoo.
Today we are going to discuss 22 pieces of legislation to
boost biomedical research and innovation, diversify clinical
trials, and improve program integrity at the FDA. While I don't
have time to discuss every bill, I did want to mention a few.
First, we have a bill from Chairwoman Eshoo authorizing the
creation of the Advanced Research Projects Agency for Health,
or ARPA-H. This proposal has the potential to be
transformative, and bring about medical breakthroughs that have
the power to change our society for the better, and I was
pleased to see that the final omnibus funding bill that
Congress passed on a bipartisan basis last week, and President
Biden signed into law, included $1 billion for ARPA-H. And now
this committee must pass comprehensive legislation to properly
establish the agency. I hope my Republican colleagues will work
together with us on the authorizing language to make ARPA-H as
effective as possible.
Next I wanted to highlight some bipartisan bills introduced
by members of our committee, as well as legislation from
Representatives--well, we have one from Chairman Eshoo, we have
another from Chairwoman DeGette, as well as legislation from
Representatives Ruiz and Blunt Rochester to improve diversity
within clinical trials, both among clinical trial participants
and investigators.
FDA, researchers, and drug manufacturers all have a role to
play in improving clinical trial diversity, and I look forward
to hearing from our witnesses about how more diverse clinical
trials cannot only improve health equity, but also improve
scientific discovery and the practice of medicine.
The committee is also continuing its work to improve
competition and reduce drug prices. A bill from Representative
Kuster would make it easier for generic drug manufacturers to
ensure their drugs are biometrically equivalent to their brand
counterparts. And it does this by improving FDA's communication
about the correct proportion of ingredients during the
application process. This bill would simplify the process for
generic manufacturers, and reduce needless delays, bringing
generic competition to market more quickly.
We will also discuss the Accelerated Approval Integrity
Act, which I introduced last week. I want to thank
Representative Maloney--I should say Chairwoman Maloney--for
her joining me on this legislative effort.
FDA's accelerated approval program has led to patients
getting faster access to medical breakthrough treatments,
including treatments of HIV and several forms of cancer. In
order to be approved under the accelerated approval program, an
investigational drug must have a positive effect on so-called
surrogate endpoint. And these endpoints can include a lab
measurement, ultrasound image, or a physical sign that is
reasonably likely to predict a clinical benefit, but is not
itself a clinical benefit.
So after being approved under this pathway, the sponsor is
responsible under FDA regulations for conducting a well-
controlled clinical trial to confirm that an actual clinical
benefit exists for patients. Unfortunately, however, under the
current system, some sponsors have failed to conduct trials in
a timely manner. For example, take Aduhelm, the Alzheimer's
drug that was approved by FDA last June. Here we are, nine
months later, and the sponsor has not screened a single patient
for its required confirmatory trial.
Other drugs have stayed on the market for 8 or 9 years
without proving a clinical benefit. And as Dr. Cavazzoni
testified last month, the process for removing these drugs from
the market is cumbersome, and can take months or even years.
And patients, I think, deserve to know that the drugs they are
taking are safe and effective.
My bill protects patients by providing FDA with the
authority it needs to ensure approved drugs provide a clinical
benefit. The bill requires that FDA and the sponsors set out a
clinical trial protocol before a drug is approved. It also
allows FDA to require that the trials are underway prior to
approving the drug. And the bill would also improve
transparency and streamline the process for withdrawing
approval when clinical trials are not conducted with due
diligence, or no clinical benefit is shown. These reforms will
strengthen the accelerated approval program and help facilitate
additional medical discoveries and product development.
So as we look to strengthen program integrity at FDA and
improve research and development, it is critical that we ensure
that we are not doing anything that could weaken FDA's gold
standard for safety and efficacy. We have to be mindful of
FDA's resources, and must always put public health and patients
first.
So I commend all the members. I couldn't describe all the
bills, but these are all excellent bills that we will be
considering, and I commend all the members for introducing the
bills before us today, and look forward to the discussion.
[The prepared statement of Mr. Pallone follows:]
Prepared Statement of Hon. Frank Pallone, Jr.
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Mr. Pallone. And I yield back the time that remains, Madam
Chair.
Ms. Eshoo. The gentleman yields back. The Chair is
delighted to recognize the gentlewoman, the ranking member of
the full committee, Representative Cathy McMorris Rodgers.
Mrs. Rodgers. Thank you, Madam Chair.
Ms. Eshoo. Good to see you.
OPENING STATEMENT OF HON. CATHY McMORRIS RODGERS, A
REPRESENTATIVE IN CONGRESS FROM THE STATE OF WASHINGTON
Mrs. Rodgers. We are considering many important bills that
support innovation for patients by improving rare disease
research, drug discovery, clinical trial diversity, and our
Nation's healthcare supply chains. Thank you, Madam Chair,
Chairman Pallone, and my colleagues for all the bipartisan
work, as we come together to reauthorize several of FDA's user
fees.
FDA's authority to collect user fees expires September
30th. And without user fees, FDA's ability to keep pace with
innovation for patients will be severely limited. So continuing
this committee's bipartisan tradition for this process is
extremely important.
This reauthorization also gives us the opportunity to
pursue other bipartisan policies related to the FDA that can
improve the review process, and ensure new cures receive
consistent, timely, and thoughtful review. I am especially
encouraged by proposals to ensure that FDA is fully equipped to
review drugs manufactured using emerging technologies, conduct
timely and dependable facility inspections, and support more
therapies and cures for rare diseases. These bills build on
previous bipartisan efforts to address drug quality and
shortage issues, and give patients a voice in drug development.
We will also consider several bills for more diverse
populations in clinical trials. During the pandemic, through
the use of digital health technologies, drug developers across
the country were able to use modernized clinical trial
protocols that allowed for greater patient involvement for more
diverse populations. We should absolutely be building on this
work.
The agenda today also includes my bill for Accelerating
Access for Patients Act. Drugs approved through accelerated
approval meet FDA's gold standard. There is strong bipartisan
support for precision medicine and the need for more innovation
and more cures, such as ALS.
Accelerated approval is how precision medicines are
approved. If we want to have drugs approved that treat diseases
before symptoms appear, it requires accelerated approval. And
here is why: traditional approval relies on a drug sponsor
showing a clinical benefit, such as a longer lifespan, or
reduction of clinical symptoms. Accelerated approval relies on
a surrogate endpoint, and that is still reasonably likely to
predict clinical benefit. So instead of a drug trial for cancer
therapy having to show you live longer, the trial can show that
the drug shrinks the tumor.
Accelerated approval also can't be used for just any
treatment. It has to be for a serious disease with an unmet
need. If we want to realize the promise of precision medicine,
such as relying on genetics and proteins to treat diseases
early, accelerated approval must be in FDA's toolkit. I cannot
support anything that undermines this important pathway.
This committee has sent a strong signal that we want
America to be the world leader in medical innovation. The
promise of a better life in lifesaving research is here in the
United States of America. We want patients to have options and
hope, especially when it comes to serious diseases with unmet
needs. Look at the 21st Century Cures Act, Right to Try and,
most recently, the Act for ALS Act.
Could there be more transparency around the pathway?
Absolutely.
Could the pathway be modernized for diseases that may not
have a clear surrogate such as ALS?
That is what I want to focus on today, as I discuss my
legislation, the Accelerating Access for Patients Act. Let's
consider together how we can expand access to promising
innovation with the appropriate guardrails in place.
Before I close, I would also like to specifically address
ARPA-H and H.R. 5585. I was disappointed that the spending bill
gave $1 billion to HHS to establish ARPA-H, which I fully
anticipate will be transferred to NIH. Just six weeks ago, this
committee heard that, in order for ARPA-H to be successful, it
needed to be independent from NIH. I have raised questions
about duplication, accountability, and strategic priorities for
ARPA-H. The Senate just moved a different proposal than the one
before Energy and Commerce.
So with no consensus in Congress whether ARPA-H is
necessary, or how it should be established, it was funded with
$1 billion of unauthorized taxpayer money anyway. That is more
than we spend each year on block grants to states for mental
health.
My concerns remain about accountability and the lack of a
clear mission for ARPA-H.
With that, I would still like to emphasize there is a great
number of ideas, important ideas before us with strong
bipartisan support. I look forward to today's discussion on
moving the FDA user fee reauthorization package through
committee.
[The prepared statement of Mrs. Rodgers follows:]
Prepared Statement of Hon. Cathy McMorris Rodgers
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Mrs. Rodgers. Thank you. I yield back.
Ms. Eshoo. The gentlewoman yields back. I would just like
to just quickly add something about ARPA-H.
I share the gentlewoman's concerns about duplication, about
bureaucracy, and the legislation is so designed so that it is
not duplicative. And while we have a difference in terms of the
dollar amount, it--well, I--what I wanted to say more more than
anything else is duplication, and a bureaucracy that can really
kill the baby in the crib, so to speak, because it is in a
place that doesn't advance what ARPA-H does.
So I look forward to working with you, every member on both
sides of the aisle, on this issue. And the clarity in the
House, I should add, is that ARPA-H should be under HHS, not in
NIH, for all of the reasons that an ARPA-DARPA model won't work
there. And that is very clear in the House, in the legislation,
in the cosponsorship with the leadership in the House, as well.
So I thank the gentlewoman, and we will always work
together.
Now, The Chair wants to remind members that, pursuant to
committee rules, all Members' written fabulous opening
statements, members, shall be made part of the record. So I
think that pleases everyone, right?
I now would like to introduce our witnesses for the panel.
Dr. Ruben Mesa is the executive director of Mays Cancer
Center at UT Health San Antonio, MD Anderson.
Welcome, and thank you for being here.
Dr. David Gaugh is the senior vice president of sciences
and regulatory affairs at the Association for Accessible
Medicines, AAM.
Welcome back to the subcommittee. We are more than pleased
to see you and have you again.
Dr. Lucy Vereshchagina, welcome to you.
She is the vice president of science and regulatory
advocacy at PhRMA.
And again, we welcome you back to the committee.
Dr. Cartier Esham is the chief scientific officer and
executive vice president of emerging companies at Biotechnology
Innovation Organization. We know the shorthand for that, BIO.
And welcome back to the subcommittee.
Dr. Jeff Allen is the president and CEO at Friends of
Cancer Research.
Welcome to you, we certainly appreciate your being here
today.
And to Dr. Reshma Ramachandran, she is the chair of Doctors
for America, the FDA task force, and a physician fellow with
the Yale National Clinical Scholars Program at the Yale School
of Medicine.
Welcome back to the subcommittee.
So thank you to each one of you for joining us today. We
look forward to your testimony.
For those--well, everyone is joining us in person, correct?
We don't have anyone virtually. I think you know what green
stands for. Yellow--just going to drive your testimony.
[Laughter.]
Ms. Eshoo. You all know what red means.
So, Dr. Mesa, we will begin with you, and all of our
thanks. You are recognized for 5 minutes.
STATEMENT OF RUBEN MESA, M.D., EXECUTIVE DIRECTOR, MAYS CANCER
CENTER, UT HEALTH SAN ANTONIO MD ANDERSON; DAVID GAUGH, SENIOR
VICE PRESIDENT, SCIENCES AND REGULATORY AFFAIRS, ASSOCIATION
FOR ACCESSIBLE MEDICINES; LUCY VERESHCHAGINA, PH.D., VICE
PRESIDENT, SCIENCE AND REGULATORY ADVOCACY, PHARMACEUTICAL
RESEARCH AND MANUFACTURERS OF AMERICA; CARTIER ESHAM, PH.D.,
CHIEF SCIENTIFIC OFFICER, EXECUTIVE VICE PRESIDENT, EMERGING
COMPANIES, BIOTECHNOLOGY INNOVATION ORGANIZATION; JEFF ALLEN,
PH.D., PRESIDENT AND CEO, FRIENDS OF CANCER RESEARCH; AND
RESHMA RAMACHANDRAN, M.D., CHAIR, DOCTORS FOR AMERICA FDA TASK
FORCE, PHYSICIAN-FELLOW, YALE NATIONAL CLINICIAN SCHOLARS
PROGRAM, YALE SCHOOL OF MEDICINE
STATEMENT OF RUBEN MESA, M.D.
Dr. Mesa. Good morning. Thank you, Chairwoman Eshoo and
Ranking Member Guthrie for the honor of participating today. I
am Dr. Ruben Mesa. I am a hematologist and oncologist, a
researcher, and a member of the national board of directors for
the Leukemia and Lymphoma Society.
But more than that, I am a son of a father lost to lung
cancer, the son of a breast cancer survivor, and I have
dedicated my life's work to changing the devastating effects of
cancer. Over that career I have been the principal investigator
or co-investigator on more than 100 clinical trials. Today at
the NCI-designated Mays Cancer Center in San Antonio, where I
am the executive director, we are providing access to nearly
200 cancer clinical trials to patients in our region in South
Texas.
Clinical trials are not a luxury for patients, but are
essential for us to be able to provide the very best care for
cancer patients. Breaking down barriers to clinical trial
participation not only promotes health justice, it is good
science. I will give you one example.
The community served by Mays Cancer Center is roughly five
million individuals, of which nearly seven percent have
Hispanic heritage. So these issues are central to our mission.
Breast cancer colleagues have found that a genetic variant near
the estrogen receptor one gene is associated with breast cancer
risk in Latinas of indigenous origin, but is absent in Latinas
of mostly European or African genetic ancestry. This genetic
variant, which is associated with lower risk of developing
breast cancer, could not have been identified in a study
without Latina patients. This discovery could lead to new
treatments that could both help Latina and non-Latino breast
cancer patients.
The lack of diversity across clinical trials today and the
systemic under-representation of certain groups weaken our
ability to develop new therapies that could improve on existing
treatments. We miss the learnings like we found related to
genetic differences in breast cancer. If we want new and better
treatments for cancer and other diseases, this is not a problem
we can afford to ignore.
Indeed, if we ignore this challenge, we will see trials
that take longer and provide less reliable data. We will be
less certain if a drug will help cure a certain group, or
whether another group will have unexpected or severe side
effects. And we will see more trials that fail to enroll enough
patients to ever know whether a promising therapy is a
breakthrough or not. And that potential breakthrough may very
well go back on the lab shelf.
My message for each of you today is we don't have to accept
that future. On the agenda today are a handful of bills aimed
at tackling these big challenges. The DEPICT Act would require
trial sponsors to incorporate diversity action plans early in
the trial design process to ensure that trials are built with
all patients in mind. Trial sponsors would look at the
demographic groups to make up their intended patient
population, and then incorporate trial plans to recruit and
retain patients from those same groups to ensure that trials
don't fail to gather data that would shape how a treatment is
used in the real world.
At Mays Cancer Center, in 2013, we mandated a similar
process, and we have increased Hispanic patient enrollment in
our interventional studies by more than 20 percent to total
almost 60 percent. The DEPICT Act would also hold FDA
accountable for modernizing trial rules that too often create
additional barriers to trial participation, and it would
empower community barriers--community providers to hire and
train trial facilitation staff and implement the IT systems
necessary to seamlessly educate and enroll patients.
The Diverse Trials Act would enhance the ability of trial
sponsors to work with trial participants to decentralize trial
services by leveraging technology to move certain activities
into a patient's home. The Diverse Trials Act would clarify
that sponsors can offer trial-relegated digital technologies,
transportation, lodging, and meals to trial participants
without the threat of legal action. At Mays Cancer Center
patients come from several hundred miles across south Texas, so
these proposed changes could really help our patients from the
Rio Grande Valley, the majority of whom are Latino and face
many health disparities.
Cures 2.0 would promote public awareness of trials as a
treatment option, calling on experts at the GAO and within HHS
to recommend actions that would promote diversity in trial
enrollment, and make clinical trials more patient friendly.
Of course, there is no silver bullet for fixing the current
lack of diversity in clinical trials. This effort will take
sustained attention and willingness to act intentionally, but
the results would be life-changing, improved outcome for
patients, more and better therapies proven to be safe and
effective, more years for patients to be with their families
living full and healthy lives. You could take real and
meaningful steps today toward that future, and I hope you will.
Thank you again for the opportunity to share my thoughts. I
look forward to answering any questions you may have. Thank
you.
[The prepared statement of Dr. Mesa follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Ms. Eshoo. Thank you, Dr. Mesa. I can't help but think on
this whole issue of diversity in the clinical trials that when
I first came to Congress women were not included in trials. Now
we find that to be almost laughable at this stage of life in
our country. So look at the progress that we have made.
But we have more to do. So--and we will, with the help of
all of the members of this very important subcommittee.
Next, Mr. Gaugh, you have 5 minutes for your testimony.
Welcome again.
STATEMENT OF DAVID GAUGH
Mr. Gaugh. Chairwoman Eshoo, Ranking Member Guthrie, and
members of the subcommittee, thank you for the opportunity to
testify about the slate of FDA-related legislation your
subcommittee is considering today, and the interplay these
bills will have with both GDUFA and BsUFA programs. My name is
David Gaugh. I am senior vice president for sciences and
regulatory affairs at the Association for Accessible Meds. I am
a licensed pharmacist, with many years of experience with both
generic and biosimilar drug industries.
AAM and its Biosimilar Councils strongly support timely
congressional reauthorization of the user fee agreements. GDUFA
and BsUFA aim to put FDA's generic and biosimilar drug program
on stable financial footing by enabling FDA to assess user fees
to supplement funding appropriated by Congress to fund critical
and measurable enhancements which provide greater
predictability and efficiency to the review of applications.
As a direct outcome, the generic and biosimilar drug
programs have increased patient access to safe, effective, and
affordable quality medicines. For ten years now, these user fee
programs have played a critical role in increasing patient
access to more affordable, generic, and biosimilar medicines.
GDUFA and BsUFA have substantially increased resources
available to FDA to review these applications. In turn, FDA and
industry have been able to significantly increase access and
affordability, with generic and biosimilar medicines providing
more than two trillion in savings to patients and healthcare
systems over the past ten years.
GDUFA 3 and BsUFA 3 are the culmination of months of
negotiation, have been subject to public review and comment,
and represent a careful balance between all stakeholders. The
commitment letters were carefully negotiated to balance the
program enhancements and the resources required to be provided
to the FDA. The agreements include a year-over-year Capacity
Planning Adjustor, or CPA, that allows FDA to automatically add
additional full-time equivalents, or FTE, resources when
increased workload criteria from the previous year exceeds
expectations.
Therefore, AAM would have concern about adding policies
into the reauthorization package that require additional FTEs
to implement if the package does not also include corresponding
appropriations. Adding such policies would increase industry's
year-over-year cost, which was negotiated and agreed upon with
the FDA by the CPA.
With that context in mind, AAM and the Biosimilars Council
appreciate the opportunity to testify on proposals relevant to
the generic and biosimilar industry, and engage with members on
these areas of interest.
In my written testimony I provided specific feedback on
proposals noticed in today's hearing that could impact access
to high-quality, more affordable generic and biosimilar
medicines.
In closing, we strongly support timely reauthorization of
GDUFA and BsUFA. We look forward to working with members of
both parties to accomplish this goal. We are grateful to the
committee's thoughtful oversight of the key issues affecting
the user fee programs. And with that I will close and thank you
for the opportunity to testify, and I look forward to any
questions you might have. Thank you.
[The prepared statement of Mr. Gaugh follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Ms. Eshoo. Wonderful, thank you, Mr. Gaugh.
Next, Dr. Vereshchagina, you are recognized for 5 minutes.
STATEMENT OF LUCY VERESHCHAGINA, Ph.D.
Dr. Vereshchagina. Good morning, Chairwoman Eshoo, Ranking
Member Guthrie, and the members of the subcommittee. My name is
Lucy Vereshchagina. I am vice president, science and regulatory
advocacy at the Pharmaceutical Research and Manufacturers of
America, or PhRMA.
PhRMA represents the country's leading innovative
biopharmaceutical research companies, which are devoted to
researching and developing medicines that enable patients to
live longer, healthier, and more productive lives. I am pleased
to appear before you today on behalf of PhRMA, and we welcome
the opportunity to discuss the various policy proposals under
consideration by the committee.
PhRMA's key priority remains timely reauthorization of the
Prescription Drug User Fee Act, PDUFA, and the Biosimilars User
Fee Act, BsUFA, prior to the expiration of these programs later
this year. These programs are critical for ensuring patients
have timely access to lifesaving medicines. PhRMA and its
member companies strongly support the PDUFA 7 and BsUFA 3
agreements, as negotiated, and are committed to working closely
with Congress, FDA, and all stakeholders to ensure the
continued success of these programs.
The agreements were carefully considered by the
biopharmaceutical industry and negotiated with FDA to ensure
that the agency is equipped with the necessary resources to
help us deliver new treatments and cures to meet patients'
unmet medical needs. These agreements were negotiated in a
transparent manner with patient organizations, and other
engagements with FDA through dedicated stakeholder discussions
and public meetings. As such, we would be concerned with any
policy proposals and legislative riders that would undermine
the negotiated user fee agreements and threaten timely passage.
There are several policy areas under consideration at the
hearing today and--that I would like to highlight.
First, as the committee is considering legislative changes
to the accelerated approval pathway, it is important to note
that this pathway has provided timely access to more than 200
treatments for HIV AIDS, cancers, and rare diseases. These
products are approved under the same rigorous standards of
safety and efficacy as traditional approvals.
Moreover, PDUFA 7 requires FDA to update their review
process, including earlier discussions in agreement with
sponsors on post-marketing requirements for drugs and biologics
approved under this pathway.
PhRMA member companies are committed to providing patients
with safe, effective, and high-quality, innovative therapies,
and accelerated approval pathway helps further this goal. It is
this critical tool for patients and regulators, and the
industry continues to support the pathway in its current form.
Second, preserving incentives for rare disease drug
development, including those under the Orphan Drug Act, are
critical for continued research and development that is
providing hope to millions of Americans with rare diseases who
still do not have access to FDA-approved treatments. Rare
pediatric cancers, in particular, are a very challenging area
of research and development, presenting unique scientific,
ethical, and logistical considerations.
The last user fee reauthorization in 2017 included new
requirements for pediatric studies of certain oncology drugs.
It also requires U.S. Government Accountability Office to study
and report to Congress on the effectiveness of these new
requirements. And as the original provisions went into effect
less than two years ago, additional time is needed to fully
realize the full impact on pediatric oncology drug development.
It would be premature to make any changes or impose
additional requirements while FDA and industry continue to
implement these provisions, and before the GAO assessment
report is completed in August 2023.
Third, PhRMA believes that increasing diverse enrollment in
clinical trials is a critical step when increasing access to
medicine and improving health outcomes. We believe enhancing
clinical trial diversity is a critical component in a broader
effort to address deeply rooted disparities across the U.S.
healthcare system. PhRMA and our member companies are enhancing
diversity in clinical trials through a number of meaningful
steps. Making a real change in clinical trial diversity
requires all stakeholders, including industry, patient and
community organizations, medical providers, policymakers, and
regulators to work together to address the existing challenges.
PhRMA shares the goals of enhancing diversity in clinical
trials, and our members are taking action to do so. But
policies that would create additional mandates would reinforce,
rather than help overcome, known barriers to participation for
patients, and have serious unintended consequences, including
unfeasibly large and long studies, delayed access to medicines,
and disincentives for industry to invest in high-risk therapies
areas.
In conclusion, PhRMA urges Congress to reauthorize PDUFA
and BsUFA in a timely manner to protect against any disruption
to these critical programs. We look forward to continue to work
with committee, Members of Congress, and other stakeholders on
these important issues.
Thank you for the opportunity to provide this testimony,
and I would be happy to address any questions.
[The prepared statement of Dr. Vereshchagina follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Ms. Eshoo. Thank you very much, Doctor.
I just thought, Mr. Gaugh, are you--I hope you are not
feeling in any way diminished. You are surrounded by doctors at
the witness table.
[Laughter.]
Ms. Eshoo. So now, let's see, Dr. Esham, you are recognized
for 5 minutes. It is good to see you, and thank you.
STATEMENT OF CARTIER ESHAM, Ph.D.
Dr. Esham. Good morning. Good morning, Chairwoman Eshoo,
Ranking Member Guthrie, Chairman Pallone, and Ranking Member
McMorris Rodgers, and members of the committee. My name is
Cartier Esham, and I am the chief scientific officer at the
Biotechnology Innovation Organization, or BIO.
BIO is the world's largest trade association representing
biotechnology companies, State biotechnology centers, and
related organizations across the United States and in more than
30 nations. While our membership includes most of the large
international biopharmaceutical companies, the majority of our
members are small, pre-revenue companies working on cutting-
edge biomedical innovations.
We appreciate the opportunity to speak with you today about
key priorities we believe will enable biopharmaceutical
companies to modernize the clinical development paradigm to one
that is more patient-centric, effective, and inclusive, and
needed to develop next generation medicines that will improve
the lives of the patients and their families that we serve.
We also want to take this opportunity to urge timely
reauthorization of PDUFA 7 and BsUFA 3 that will serve to
advance those goals, as well as improve regulatory
transparency, oversight, and ensure that the FDA is best able
to carry out its vital mission to protect and promote public
health.
Congress has built a strong foundation over many years that
have collectively worked to ensure effective and timely
reviews, improved drug and biologic safety monitoring, enable
the agency to keep pace with medical and scientific
advancements, and provided the support necessary to ensure that
advanced medicines are provided to patients as quickly and
safely as possible. We look forward to working with this
committee to build on those efforts as we discuss the user fee
agreements and proposed legislation under consideration.
The PDUFA and BsUFA agreements will build upon these
previous efforts and foster next generation scientific efforts.
For example, PDUFA 7 will continue to advance the utilization
of patient-centric drug development and review processes,
expand our ability to utilize real-world evidence, strengthen
the FDA safety monitoring capabilities, and ensure that the FDA
is able to meet the demands and opportunities of the digital
age by improving the agency's analytical capabilities, and
supporting the use of digital technologies, which have the
potential to reduce patient burden and more effectively capture
information about clinical outcomes for all patients.
I would also like to take this opportunity to convey BIO's
commitment to improving clinical trial diversity. The COVID
pandemic highlighted the urgent need to remove barriers and
advance solutions that enable clinical trials to be more
representative of the patients being treated. It also
highlighted methodologies, tools, and approaches that have the
potential to tear down some of those barriers. PDUFA 7 will
advance the acceptance of real-world evidence and data and
digital technology tools, which we believe are key to advancing
a clinical development ecosystem that is more expansive,
inclusive, and less burdensome to patients.
We have also provided this committee with legislative
proposals we believe would further remove barriers and
establish a regulatory framework that will drive change and
support a clinical development ecosystem that is more inclusive
and representative of the patients we serve, including
establishing processes and understandings about how and when to
establish enrollment targets, new approaches to inclusion and
exclusion criteria, how to design and implement trials that are
less burdensome to patients, and better enable evidence
collection that improves our collective understandings of
health outcomes for all patients.
Before I close, I would also like to convey our continued
support for the accelerated approval pathway. As previously
mentioned, well over 200 drugs and biologics to treat serious
or life-threatening diseases or--and conditions with high unmet
medical needs have been approved using this pathway, extending
lives in certain cases and saving lives by providing novel
therapies that met FDA's well-established approval standards
for safety and effectiveness earlier than would have been
possible without its existence.
The PDUFA 7 agreement includes commitments that will
further strengthen this pathway by advancing regulatory
understandings about what is necessary to support the
utilization of a surrogate endpoint as a basis for approval. It
includes revisions to improve processes to allow for more
effective dialog and design of assessments of PMR needs and
study designs, and improve the continued evaluation of PMR
post-approvals to ensure requirements are being met and/or
remain scientifically valid.
We look forward to working with Congress to ensure timely
enactment of PDUFA 7 and BsUFA 3, and are committed to working
to advance a new clinical development paradigm that is more
expansive, inclusive, patient-centric, and supports the
development and timely delivery of next generation medicines
that will improve the lives of patients and their families.
Thank you.
[The prepared statement of Dr. Esham follows:]
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Ms. Eshoo. Thank you, Dr. Esham.
Dr. Allen, you are recognized for your 5 minutes of
testimony, and welcome again, and thank you.
STATEMENT OF JEFF ALLEN, Ph.D.
Dr. Allen. Thank you, and good morning, Chairwoman Eshoo,
Ranking Member Guthrie, and members of the committee.
Ms. Eshoo. Move your microphone a little closer.
Dr. Allen. Sure.
Ms. Eshoo. We don't want to miss a word.
Dr. Allen. All right, thank you. I am Jeff Allen, president
and CEO of Friends of Cancer Research, an advocacy organization
dedicated to the acceleration of science and technology, from
bench to bedside. Thank you for holding this important hearing
to modernize numerous aspects of regulation and research.
This is a unique opportunity to address a diverse set of
issues critical to making progress against illnesses like
cancer, neurological disorders, and the over 6,500 rare
diseases that currently have no treatments.
In order to improve the government's capability to speed
research, this committee has taken on the important work to
authorize the Advanced Research Project Agency for Health. We
believe that ARPA-H can serve a unique role of catalyzing
transformational technologies that have broad applicability
across multiple disease areas.
An additional effort of this committee is to enhance
scientific infrastructure and accessibility to new medicines
through the 21st Century Cures Initiative. The Cures 2.0 bill,
championed by Representatives DeGette and Upton, builds on
numerous provisions of its predecessor that have proven to be
highly effective at promoting development and facilitating
access to innovative therapies. While efficient processes and a
robust research infrastructure are necessary, barriers to
clinical trials present a perennial challenge.
For decades, the average enrollment of adults with cancer
in clinical trials has hovered around two to eight percent.
Several of the bills included in today's hearing will help make
clinical trials more inclusive, accessible, and equitable. Many
of these would grant more people access to trials as part of
their care, and provide clinical evidence for a more
representative population.
While there are many topics being discussed today, several
of which I have addressed in my written testimony, I want to
focus today on efforts to optimize the accelerated approval
process. Accelerated approval allows for a drug to come to
market based on a surrogate or intermediate endpoint that is
reasonably likely to predict clinical benefit and, it is
reserved for drugs to treat serious and life-threatening
conditions. This broadly applies to all drug classes.
However, due to available surrogate endpoints and the
scientific advancements to treat cancer in the past 10 years,
80 percent of the accelerated approvals were granted for
oncology indications. A recent assessment by the FDA concluded
that cancer therapy is receiving accelerated approval, where
available, a median of 3.4 years earlier than if approval were
based on a full clinical endpoint, such as overall survival.
Products approved through the accelerated approval process
are subject to post-approval study requirements to verify the
anticipated effect of the drug. In evaluating the total number
of indications that have received accelerated approval, 49.3 of
all indications have been converted to full approval based on
subsequent evidence. Conversely, only 9.9 percent of
accelerated approvals have been withdrawn. This yields 40.8
percent of pending indications that have neither been converted
nor withdrawn. Together, this indicates a highly favorable
success rate for confirmation of benefit, and demonstrates the
importance of timely post-approval studies.
In evaluating the time needed to develop post-approval
evidence, studies resulting in conversion to full approval took
a median of 3.1 years. Withdrawals occurred at a median of 3.8
years. Of the pending oncology indications, 72 percent have
been approved in the last two years. Given that it may take
three to four years to develop the necessary data, it may be
unrealistic to expect these pending studies to have already
been completed.
These data indicate that the accelerated approval is
working as intended. It has enabled patients with serious
diseases to have access to new medicines years earlier. But
this pathway can and should be improved to maximize the
benefits. Key to continued success is both early planning when
accelerated approval may be used, and transparency to robust,
post-approval evidence generation. Together, this will enhance
confidence in the process and bolster the ability to address
unmet needs for patients.
Through the leadership of this committee, we can enable a
strong research and evidence infrastructure, implement clinical
trials that are more equitable and accessible, and ensure that
avenues are available to speed access to promising new, safe,
and effective medicines. For the millions of patients across
this country who are currently dependent on safe and effective
medicines, and for those who are holding strong for the
breakthroughs to come, there isn't time to waste.
Thank you, and I look forward to answering your questions
today.
[The prepared statement of Dr. Allen follows:]
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Ms. Eshoo. Thank you, Dr. Allen.
And last, but not least, Dr. Ramachandran, for your 5
minutes of testimony. And again, thank you, and welcome back.
STATEMENT OF RESHMA RAMACHANDRAN, M.D., M.P.P.
Dr. Ramachandran. Thank you. Chairwoman Eshoo, Ranking
Member Guthrie, and distinguished members of the Subcommittee,
thank you for the invitation to testify today. My name is
Reshma Ramachandran. I am a physician and researcher in the
National Clinician Scholars Program at Yale School of Medicine.
I also lead the Doctors for America FDA Task Force, which is an
independent group of physicians working together to support and
strengthen the FDA toward ensuring meaningful clinical outcomes
for our patients. My remarks reflect my own views, and not that
of my employers nor the organizations I work with.
While I understand that the subcommittee is considering
several bills related to enabling access to innovative, safe,
and effective health technologies, my remarks today will be
focused on just two areas.
First, reforms to the accelerated approval pathway that
rebalance early access to promising treatments with oversight
to ensure that these treatments are truly effective and safe
are urgently needed. Nearly half of the 253 accelerated
approval drugs approved by the FDA between 1992 and 2020 have
not been confirmed to be clinically effective. Just last year,
the FDA maintained marketing authorization of four cancer drug
indications, despite their required post-approval studies
failing to confirm clinical benefit.
Moreover, relying on real-world evidence to confirm
clinical benefit has not been shown to work. Of the 50 required
confirmatory trials for drugs granted accelerated approval by
the FDA between 2 and 2018, none could be feasibly emulated
using available real-world evidence.
Such a lack of oversight by the FDA in allowing
manufacturers to continue to market unproven drugs can lead to
harms for our patients and us, as clinicians.
First, we may be unknowingly prescribing treatments of
limited or no meaningful benefit to our patients. For those
conditions where there may be an available and proven
alternative, this may create an unfortunate opportunity cost
for patients, both therapeutically and financially.
Second, payers may be required to provide coverage for such
treatments, causing patients prescribed these drugs to incur
costly out-of-pocket payments, and other beneficiaries to
potentially pay higher premiums.
Reforms within the Accelerated Approval Integrity Act offer
a crucial opportunity to recenter the expedited review pathway
around patients. Importantly, the bill would enable FDA
oversight over the design and start of post-approval studies to
prevent against any delays in initiating confirmatory trials,
and ensure that these required studies examine the critical
question of whether these drugs are truly beneficial for our
patients.
Sponsors would also have to routinely report to the FDA on
progress in completing these studies, allowing the agency to
assist if there are any roadblocks. Should the drug fail to
show clinical benefit, or their sponsors lag behind in
completing required post-approval studies, FDA would be able to
withdraw these accelerated approval drugs more efficiently and
prevent patient harm.
Finally, accelerated approvals where sponsors either fail
to confirm clinical benefit or fail to report their progress in
doing so will automatically be withdrawn after an ample period
of time.
This robust legislation could be strengthened even further.
Namely, FDA, in having oversight of post-approval study design,
could also ensure that clinical endpoints are being studied,
not surrogate ones, and definitely not the same ones that are
used in trials supporting accelerated approval.
Reports submitted to the FDA on progress in completing
post-approval studies should also be made public, and any
results from these studies should be made immediately
available. Not only would this enable public accountability of
such approvals, but it would also inform how we, as clinicians,
take care of our patients, especially if a drug is found not to
be beneficial.
Further fueling uncertainty of whether FDA-approved
treatment is beneficial for patients is a lack of
representation within clinical trials. To date, FDA's laudable
efforts to address these gender, age, and racial disparities in
clinical trial enrollment have fallen short in moving industry
sponsors to act. Data from the FDA's drug trial snapshot, a
publicly available webpage with demographic information of
participants enrolled in pivotal trials of newly approved drugs
and biologics, showed only 20 percent reported clinical
benefits and risks for Black patients, a figure that did not
improve over the 8-year period that was assessed.
The DEPICT Act includes provisions to ensure that industry
sponsors not only promise to enroll diverse and representative
participants into clinical trials, but actually do so, by
setting clear targets for enrollment based on disease
prevalence data. Should sponsors fail to enroll trial
participants representative of the patients who would be
ultimately prescribed the treatment, FDA would then require
post-approval studies to demonstrate treatment benefit across
various demographic subgroups. Should disease prevalence data
not be available, FDA should set a floor for clinical trial
enrollment targets that reflect available national demographic
sub-population data.
In my written testimony I further discussed these areas and
others being considered by the subcommittee where legislative
action could have a profound impact on improving the lives of
my patients and the American public.
Thank you again for this opportunity. I am happy to answer
any questions you might have.
[The prepared statement of Dr. Ramachandran follows:]
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Ms. Eshoo. Thank you very much, Doctor. Now, so this--
colleagues, this concludes the testimony of our witnesses. We
will now move to member questions. And I recognize myself--
surprise, surprise--for 5 minutes. How is that?
And I am going to start with one of my favorite subjects to
set the stage. Let me ask each witness, do you support H.R.
5585? That is the ARPA-H legislation.
Dr. Mesa?
Dr. Mesa. Yes, I do.
Ms. Eshoo. Mr. Gaugh?
Mr. Gaugh. Yes.
Ms. Eshoo. Thank you.
Dr.--I am going to get your name right--Vereshchagina.
Dr. Vereshchagina. PhRMA believes that ARPA-H should be
narrowly focused on increasing R&D investments in areas of high
scientific and regulatory uncertainty that may not be currently
pursued by other public or private sector entities.
You talked this morning about avoiding duplication. So that
is our comment.
Ms. Eshoo. Wonderful. I take that as a yes.
Dr. Esham?
Dr. Esham. Yes, we are supportive of ARPA-H, and with the--
we thank Congress for the enactment and funding the
establishment of ARPA-H and the funding for ARPA-H, and we want
to work with you on the bill, now that that law has been
passed, to sort of, you know, ensure that--as you said, we do
think it is very important that this agency has the ability to
act independently, and has the--and able to embark on the
nimble spirit, I believe was your turn of phrase, which I think
we very much relate to, to ensure it is able to best meet its
unique and transformative mission.
Ms. Eshoo. Wonderful. Thank you, Doctor.
Dr. Allen?
Dr. Allen. Yes. We support the formation and authorization
of ARPA-H.
Ms. Eshoo. Wonderful.
And Dr. Ramachandran?
Dr. Ramachandran. You can call me Dr. Ram.
[Laughter.]
Dr. Ramachandran. Yes, I support the ARPA-H, especially if
it includes provisions to ensure that access and affordability
are built into the innovation model, so that Americans and
taxpayers can benefit from federally funded research.
Ms. Eshoo. Thank you very much.
Now to Dr. Mesa, as you said in your testimony, you are a
principal investigator of more than 100 clinical trials. So you
have incredible experience in this area. Do you support 6584,
the DEPICT Act? Do you think that this is directed and shaped
to produce the outcomes that we are looking for, given your
vast experience?
Dr. Mesa. Yes, I think it could be a very impactful bill.
As we think about the barriers that patients can face for
diversity in clinical trials, I think there is many aspects of
it that can be very impactful.
First, recognizing that there is not one solution.
Ms. Eshoo. Right.
Dr. Mesa. You know, as we look at patients, they are all
different. They all have different complexities. They all have
different barriers, you know. So trying to create parts that
really focus on the patient's part of that equation, trying to
overcome a lack of health literacy, pre-conceived notions about
clinical trials, trying to overcome personal aspects in terms
of barriers to care, transportation limitations----
Ms. Eshoo. Yes.
Dr. Mesa [continuing]. You know, telemedicine solutions for
increasing feasibility, so there is really a patient piece to
this.
The second part is really in the conduct of the trial
itself, how the trial is designed, its eligibility criteria. I
will use, for example, there are certain boilerplate
eligibility criteria that sometimes can really be pre-
discriminatory, such as relates to hepatic function or liver
function. There is higher rates of elevated liver function
tests in South Texas that can just kind of automatically start
to exclude a group of patients.
Ms. Eshoo. Let me--because I only have 5 minutes, and I
have 1:12 left, does the FDA currently have any legally binding
standards for diversity in clinical trials?
Dr. Mesa. Unfortunately, there is no minimum standard at
the current time.
Ms. Eshoo. Now, at the Mays Cancer Center you require that
each new trial put in place--the abbreviation is M-A-P, MAP,
Minority Accrual Plan. That includes enrollment projections,
demographics, specific strategies. This is, I think, very
similar to the Diversity Action Plan.
Can you tell us how what you are doing with MAP, M-A-P, how
that has led to new scientific discoveries if, in fact, that
has happened, and--or how it has affected enrollment in the
trials?
Dr. Mesa. So I will use an example for a disease that is
over-represented in African Americans, multiple myeloma----
Ms. Eshoo. Right.
Dr. Mesa [continuing]. Where the Minority Action Plan for
those trials specifically included outreach to African American
churches, you know, and other groups in our community in south
Texas to increase awareness and try to decrease barriers.
Ms. Eshoo. Excellent. Well, my time has expired, so thank
you to each one of you.
The Chair now recognizes our wonderful ranking member, Mr.
Guthrie, for his 5 minutes of questions.
Mr. Guthrie. Thank you, Madam Chair.
First, I have a letter in support of my bill, 7008 H.R.
(sic) that has been given to the staff, your----
Ms. Eshoo. So ordered.
[The information appears at the conclusion of the hearing.]
Mr. Guthrie. OK, thank you. And I would like to especially
thank the Academy of Managed Care Pharmacy for their support on
the letter.
So, Dr. Vereshchagina, I want to ask you these questions.
So the intent of the pre-approval information exchange is not
so PhRMA can advertise before a drug is out. That is absolutely
not the intent--before it is approved. But for healthcare
plans--so plans, payers--to have the information, knowing what
is coming down the pike, so we can get payment. So getting
approval of a drug without payment of a drug sometimes keeps
people from having access to a drug. And so what we want to do
is shorten that time, the valley of death, particularly
blockbuster drugs moving forward.
And I know that has been shared--interest shared by the
FDA. So in 2018 they put guidance. And so my question, Dr.
Vereshchagina, is there--what has been the experience of your
member companies since the guidance has come out in 2018?
Dr. Vereshchagina. Thank you for the question. So, as you
mentioned, the FDA finalized the guidance on the issue, and our
member companies find this FDA guidance very helpful and very
impactful. And in fact, between 2017 and 2021 the number of
publicly announced, value-based contracts has more than
doubled. So we are seeing real positive impact of FDA giving
very clear guidance on this issue.
So in my understanding--and I am not a healthcare coverage
expert, I am an FDA regulatory expert--but my understanding
that many of these contracts showing benefit and reducing
patient costs and reducing overall medical costs. And if you
would like any additional details or numbers on this, I would
be happy to get back to you.
But again, the bottom line, that FDA's final guidance
yielded real benefits, and helped manufacturers and payers work
together and share the information to make sure that new
medicines are accessible and affordable for patients.
Mr. Guthrie. Well, thank you. As we are--as I talked about
in my exciting opening statement, there--the innovation that is
coming--and a lot of it is extremely expensive. I mean, it is
expensive research. It is expensive to do. Like, you know, the
cure that they have now of sickle cell anemia is a bone marrow
transplant, I believe. So--which is fantastic that we can cure
sickle cell anemia for people that are suffering from it,
absolutely. But having access to it is also important.
And so we are looking at value-based agreements, Dr.
Schrader and I, a colleague--I guess he is on the committee,
but he will be here in a little while. We are--how do you pay
for that?
And so I know a lot of the innovators, the manufacturers,
are willing to take on some of the risks to say, hey, this
cannot meet the clinical desire that we have. So like a
Medicaid system, instead of paying everything up front, may pay
over time. And if they don't get the results, then have to
pay--then they don't--it is pay-for-performance sort of, I
guess, value, the value of it.
And so how would--the problem is that is not just you
setting a price, and then the payer deciding whether or not
they want to meet the price, and negotiating over a price. It
is negotiating over a lot of issues to come up with the value-
based agreements. So how would information pre-approval be
beneficial to value-based agreements?
Dr. Vereshchagina. So as I mentioned, I am not a expert in
value-based contracts or coverage overall, but transparency and
open communications and ability of industry, working with FDA
and sharing the information, has been helpful and, as I
mentioned, from the numbers we have seen, really resulted in a
tangible improvement in the sharing of the information.
Mr. Guthrie. OK, thanks. So the idea is that, if a drug is
going to be approved, we see it is on the pathway to being
approved--well, the issue is, once a drug is approved, you
don't really get--a lot of people don't get access to it until
it is paid for. Do they have access to it--somebody to help
their insurance to pay for it, or the payer pay for it? Because
it is just--a lot of it is just too expensive.
And so, if you can see a drug move into approval, and you
can have those discussions over--beforehand, it shrinks the
valley of death, as it is called, or the difference between the
day the drug is approved and the day the payer has it in their
formulary to pay for. And that is the intent, and that is what
we are trying to do, not trying to push FDA to approve drugs
that aren't ready to be approved, but having the gap between
access to a blockbuster drug and--approval of blockbuster drug
and access.
So thank you very much, and I will yield. And I will yield
back.
Ms. Eshoo. The gentleman yields back. The Chair now
recognizes the chairman of the full committee, Mr. Pallone, for
your 5 minutes of questions.
Mr. Pallone. Thank you, Chairwoman Eshoo. At our hearing
last month, Dr. Cavazzoni from FDA explained how it would be
helpful to allow FDA to require drug sponsors of accelerated
approval drugs to begin their confirmatory trials before the
drug is approved, and the current cumbersome process that FDA
has to follow to withdraw an approval from a drug that has not
shown a clinical benefit for patients. And with that in mind I
introduced H.R. 6963, the Accelerated Approval Integrity Act,
that I mentioned in my opening statement.
So I wanted to ask Dr. Ramachandran, can you describe why
it is important for patients and providers that manufacturers
complete these confirmatory trials in a timely manner?
And what policies would ensure that drugs that do not
complete their confirmatory trials come off the market?
Dr. Ramachandran. Yes. Thank you so much, Chairman, for the
question.
It is critically important for our patients and us, as
clinicians, to know the true benefit and safety, especially for
these drugs that are being approved fairly early on, and are
allowing us earlier access to them.
The reason why these post-approval studies were so
important is that we are prescribing these drugs with a lot of
uncertainty to our patients. And so having these studies
completed in a timely manner, and knowing exactly that they are
truly clinically beneficial, that that surrogate endpoint that
the drug was initially approved on is predictive, and does
demonstrate clinical benefit for our patients is important.
If it doesn't show that, and it continues to linger on the
market, unfortunately, you know, if there is a proven
alternative option, our patients won't be accessing that.
Instead, they might be stuck on this accelerated approval drug
with no clinical benefit or, worse, something that might be
potentially unsafe. On top of that, the financial ramifications
are pretty incredible for patients who are taking drugs of
unproven benefit.
As an example, there is a drug called pembrolizumab, which
is a cancer drug for liver cancer and also metastatic
urothelial cancer, where the post-approval studies were
actually found to be negative. FDA continued to let the drug on
the market, and it cost patients about $13,000. This is before
insurance, of course, but high, very high co-pays per month to
be able to access this drug. So the financial ramifications for
both patients and payers are pretty incredible.
Some of the provisions that were in the bill that you have
introduced are very strong, in terms of allowing and making
sure that there is FDA oversight in terms of the study design,
but more importantly, ensuring that there is a process, and
with clear criteria, for FDA to withdraw these drugs in a
efficient manner, so that patients aren't incurring these
harms.
And the automatic expiration provision is particularly
critical to make sure that these drugs aren't lingering while
we are waiting for sponsors and the FDA to kind of go back and
forth in terms of whether or not the drug should continue to
stay on the market.
Mr. Pallone. All right, let me ask you another question.
There are proposals before us today--you know, bills today--
that address the accelerated approval pathway in a different
way. And I am concerned that these measures may unintentionally
lower current standards for safety and efficacy.
So can you describe the importance of having a strong
safety standard and a clear efficacy standard for the
accelerated approval pathway, and the risk to patients if we go
too far in opening up this accelerated approval process?
Dr. Ramachandran. Yes, there has been some proposals to
allow for real-world evidence or observational data, both in
Cures 2.0 and in other legislation that would be enough to
fulfill the post-approval studies that are required for
accelerated approval. Unfortunately, we have done a number of
studies--or our research group at Yale--that have shown that,
if we try to replicate those confirmatory trials using real-
world evidence or observational studies, we are not able to do
so.
So, you know, with the currently available real-world
evidence, it is not sufficient to be able to show clinical
benefit or safety. And having, you know, robust study design is
incredibly important for us, as clinicians, to know that it is
actually preventing death or hospitalization, things that
matter for our patients, instead of taking something that could
be potentially toxic or unsafe, and not just--might not work.
And, you know, I should remind folks that, you know,
chemotherapy, you know, that is often times used for cancer
treatment, it is not an easy drug to take. Our patients suffer
incredible side effects from taking these types of medications,
even though they might be lifesaving. So the longer period of
time we allow for patients taking these drugs that might be
unproven, but on top of that have very, very, you know, serious
side effects on the market, it takes a toll on them. And you
can imagine what sort of false hope it could bring if the drug
is found to be unproven, but still allowed to be on the market
by the FDA.
Mr. Pallone. Now, I think you mentioned the use of real-
world evidence, so just--there is only 30 seconds, but----
Dr. Ramachandran. Yes.
Mr. Pallone [continuing]. What does the current data say
about researchers' ability to prove the clinical benefit of
accelerated approval based on real-world evidence?
Dr. Ramachandran. It is very limited, at least with current
sources that we have. We did a study actually looking at real-
world evidence for a number of drugs, accelerated approval or
otherwise. And we only found that 15 percent of the trials
could be replicated with real-world evidence, suggesting that
that data source is just not sufficient right now, in terms of
being able to show true clinical benefit and safety for
patients.
Mr. Pallone. All right, thank you. I yield back.
Thank you, Madam Chair.
Dr. Ramachandran. Thank you.
Ms. Eshoo. The chairman yields back.
The Chair now recognizes the ranking member of the full
committee, Mrs. McMorris Rodgers, for your 5 minutes of
questions.
Mrs. Rodgers. Thank you, Madam Chair.
Mr. Allen, is the accelerated pathway working for cancer
therapies and patients who need those treatments?
Dr. Allen. It is. You know, over the last 30 years, since
the pathway was implemented, at least in recent years, an
average of 30 percent of all oncology drugs have gone through
the accelerated approval pathway. And of those, under ten
percent have failed to confirm their benefit.
I think that this is due--in large part, due to the efforts
of the cancer community to standardize these measures, and
research them in order to improve their reliability. What this
has resulted in is access to these products years earlier,
often times where there was no current available therapy.
Mrs. Rodgers. Thank you. Some of the witnesses have
suggested that post-approval studies should use clinical
endpoints, rather than surrogates. What would this mean for
cancer patients?
Dr. Allen. I think it is a very good point, but it is also
worth diving into the data here. In oncology, there have been a
couple of instances where a surrogate endpoint, such as tumor
size reduction, for example, is used in a number of cases for
the basis of an accelerated approval. So that is the surrogate
endpoint.
It also has been used in a couple of blood cancers because
of the overall impact on those endpoints. Specifically, overall
major psychologic response or complete response, meaning the
cancer has been eradicated.
So while that isn't the same as a long-term overall
survival endpoint, the eradication of cancer, I think, is a
notable clinical benefit here. And so I think that is--these
drugs have changed the treatment of certain leukemia. So I
don't think this is the area where we need to be focusing the
attention of improvements to this pathway.
Mrs. Rodgers. Thank you.
Dr. Esham, your testimony today speaks to how effective the
accelerated approval pathway has been in reviewing and
delivering safe and timely therapies to patients with serious
or life-threatening conditions. Why has the accelerated
approval pathway been so successful for bringing new therapies
to certain patient groups like those with cancer, but not for
others, like those suffering from ALS?
Dr. Esham. Thank you for that question. We have long
advocated for the development of surrogate and intermediary
clinical endpoints across more disease areas.
We have also advocated for more consistent practices across
FDA about what evidence is needed to support the utilization of
surrogate and intermediate--intermediary endpoints in more
disease states.
We hope that the provisions in PDUFA 7 that allow for early
engagement to discuss issues and criteria to support the
utilization of surrogate endpoints to support approval will
help.
We also hope that the pilot program on rare disease
endpoints will advance mutual understandings about how to meet
these criteria and enable utilization.
It is also important that the medical, patient, scientific,
and regulatory community work together to ensure that
scientifically sound surrogate endpoints are developed, and
that specific guidance is provided about how to utilize those
types of endpoints in more disease states such as ALS.
Each approval and accelerated approval does allow for more
timely access to treatment. It enables scientific
understandings of diseases to advance, and can be foundational
to continued innovation and investment in serious, complex, and
life-threatening diseases such as ALS.
Mrs. Rodgers. In the last 15 years, 56 percent of companies
that received an accelerated approval were small companies.
What factors go into whether a small company decides to pursue
the accelerated pathway for a novel drug?
And how could the threat of civil monetary penalties or an
automatic expiration of approval shape that decision?
Dr. Esham. The reason I think that you see a large number
of emerging companies utilizing the accelerated approval
pathways is because they are working on novel areas of
treatment, many times an area where there is little precedent
established. So the accelerated pathway, again, is the path
forward to ensuring that we get these first-time treatments and
novel ways to treat patients. And without the accelerated
approval, this would be greatly limited.
We do have some concerns and want to work with the
committee relating to the establishment of mandatory withdrawal
and evaluation timelines, and the potential impact that could
have on investment in these types of serious and life-
threatening diseases. And while a majority of the treatments,
as mentioned in others' testimony today, approved to date under
accelerated approval has transitioned to traditional approval
under five years, most of those approvals are evaluated based
on oncology treatment data. And we have concerns that science
hasn't moved the same way or at the same pace across all
disease states.
And even with the potential for waivers, we have
uncertainties about whether there would be consistent and
understood processes for these evaluations, whether they would
be able to be done in a timely manner, and whether they would
take into account cases where medicines are continuing to meet
benefit risk standards, but more studies are warranted, or will
be able to continue to be provided to patients.
But we do want to work with this committee to improve
processes and approaches that will strengthen the pathway, and
we commit--our commitment was clear.
And some of the provisions that were included in PDUFA--
again, discussing the criteria for surrogate endpoints,
ensuring that there is earlier engagement in the process to
determine PMR assessment needs and study designs, and improve
processes post-approval to better enable sponsors in the FDA to
engage on issue resolution where there are problems with
conducting the trial, and to determine if it is still
scientifically valid or not--and that will support efforts
around----
Mrs. Rodgers. Thank you.
Dr. Esham [continuing]. Withdrawal discussions.
And we also are supportive of the utilization of real-world
evidence. And while some have said it may not be the panacea,
we are ever moving toward better data sources, and PDUFA does
have provisions to continue to advance how we can use real-
world evidence to support post-market requirements, which may
alleviate some of the barriers that we have seen to date.
Mrs. Rodgers. Thank you. I really appreciate the
opportunity to talk about the importance and the potential of
real-world evidence in drug development, especially for certain
populations, like those with intellectual disabilities or the
rare diseases.
And thank you for the time, Madam Chair. I yield back.
Ms. Eshoo. You are a beautiful voice for those that you
just spoke to, and we all appreciate it.
OK, we now are going to recognize the gentleman from North
Carolina, Mr. Butterfield, for your 5 minutes of questions.
Mr. Butterfield. Let me say good morning to all of you, and
thank you to The Chair and ranking member for including two of
my bills in today's hearings. They are H.R. 6972--we call it
the Give Kids a Chance Act, which was introduced by myself and
my fellow co-chair of the Childhood Cancer Caucus, Mr. McCaul.
And the second piece of legislation is H.R. 1730, the Speeding
Therapy Access Today Act--we call it the STAT Act--introduced
by my fellow co-chair of the Rare Disease Caucus, my friend
from Florida, Mr. Bilirakis. Both bills, Madam Chair, address
critical medical needs, more treatments, and cures for
pediatric cancers and rare diseases.
And so I want to continue with you, Dr. Esham, if I can.
The Give Kids a Chance builds on the Race for Children Act,
which was supported by many, many members of this committee.
The bill provides the FDA with the authority to direct
pediatric studies of combinations of cancer drugs. And this is
important because cancer researchers tell us that it is
unlikely that one drug will work for all cancer patients. Many
patients, both adults and children, may need combinations,
combinations of therapies to fight their disease.
And so, Dr. Esham, thank you for your testimony. Thank you
for sharing your industry's commitment to pediatric patients.
We are--well, what are some of the challenges that biotech
companies face when making cancer drugs for children?
Dr. Esham. Thank you for that question. You know, the
development of therapeutics for childhood cancer does have its
challenges.
First, it is very rare, and the etiology and biology of
cancers that occur in children can differ from those that occur
in adults. So immediate extrapolation of efficacy and safety is
not always possible.
We need to balance the desire to enroll children in
clinical trials in recognizing that--particularly when current
modality treatments provide clear benefits. So we don't want
children placed at a disadvantage of being enrolled in a
clinical trial that has undue exposure to risks, or does not
provide the necessary healthcare.
I will note that, since enactment of the RACE Act, section
504, we have been working diligently with the FDA to remove
challenges and try to ensure successful and effective
implementation of that program. We are working to establish
metrics to make sure that we are taking the opportunity to
evaluate successes or challenges. The program went into effect
in August 2020, and implementation guidance was published in
2021. So we are, again, working very diligently to try to
ensure----
Mr. Butterfield. Thank you for that. I am going to have to
move onto the STAT Act.
Dr. Esham [continuing]. Effective, yes.
Mr. Butterfield. I am going to have to move on to the STAT
Act in just a moment.
Dr. Esham. Yes.
Mr. Butterfield. But let me just say for the record that it
is important to just know that the Give Kids a Chance Act--that
the FDA would not be given unlimited authority. I want all of
my colleagues to know that, it is not a grant of unlimited
authority. The bill will set rigorous scientific standards and
extend waivers and defer protections to those new studies. And
so I just want the record to reflect that.
Let's move on to the STAT Act. There are over 7,000 known
rare diseases, and yet 95 percent of them do not have an FDA-
approved treatment. The STAT Act's goal is to increase rare
disease therapy development, and increase access to treatments
and cures for patients. One of the pillars of the bill is the
creation of a rare disease and condition drug advisory
committee, which advocates believe would help strengthen FDA's
rare disease activities.
And so back to you again, Dr. Esham, and we have about a
minute left. Could you speak to the potential value that
engagement with patients and providers and other experts could
bring FDA as it reviews rare disease drug applications?
Dr. Esham. Thank you. And I will say we are still reviewing
this legislation, but are committed to working with your office
to provide our thoughts. And we are supportive of efforts to
ensure that there are clear paths forward for the development
of treatments of rare diseases and how to effectively address
our unique challenges.
So we look forward to continuing to work with you on----
Mr. Butterfield. Thank you.
Dr. Esham [continuing]. On this legislation.
Mr. Butterfield. Thank you for your cooperation. Thank you
for your comments.
And I would like to thank The Chair and the ranking member
for including in today's hearings bills related to clinical
trial diversity. I will soon be introducing legislation with
other colleagues Robin Kelly, Tony Cardenas, and Yvette Clarke
of New York on clinical trial diversity with NIH-supported
trials. I look forward to working with all of you, and I wish
all of you a happy St Patrick's Day. I yield back.
Ms. Eshoo. The gentleman yields back. I can't help but
think of this on a consistent basis, Mr. Butterfield. We are
really going to miss you, a wonderful member of this committee.
But you are not gone yet. You still have----
Mr. Butterfield. Don't make me sad.
Ms. Eshoo [continuing]. A lot----
Mr. Butterfield. Don't make me sad, Madam Chair.
Ms. Eshoo. I am not going to make you sad.
Mr. Butterfield. Thank you, thank you.
Ms. Eshoo. We want to make you glad, by getting your
legislation through. So thank you for your----
Mr. Butterfield. Thank you.
Ms. Eshoo [continuing]. Terrific work. Now The Chair is so
pleased to recognize the gentleman from Michigan, Mr. Upton.
First, how are you feeling?
Mr. Upton. Well, I am doing much better today. I--for those
that didn't know, I tested COVID before that Library of
Congress event on Tuesday. So I am self-quarantined until
Saturday. I want you to know I am studying the books hard, so I
hope to pass the test Saturday so I can go back to Michigan.
[Laughter.]
Mr. Upton. I joined Buddy Carter. I know he tested
positive, as well, for that event, so I wish everybody well,
for sure.
But thanks for your----
Ms. Eshoo. Well, please take good care. Please take careful
care. You are very important----
Mr. Upton. I am drinking lots of liquid----
Ms. Eshoo [continuing]. To all of us.
Mr. Upton. It is my first Saint Patty's Day without a
Guinness, ever. So----
[Laughter.]
Ms. Eshoo. You can't have a Guinness when you have COVID?
Mr. Upton. I am not having a Guinness, although they say
that is healthy. It is good for your heart. I am not going to
take that advice today.
Ms. Eshoo. I would take a few sips----
[Laughter.]
Ms. Eshoo [continuing]. Fred. OK, we are not going to
penalize you for the time we are gabbing, so----
Mr. Upton. All right, yes, I am----
Ms. Eshoo. Let's set the clock for five.
Mr. Upton. We have 3 seconds left on the clock.
Ms. Eshoo. There you go. No, no, there you go.
Mr. Upton. All right. Well, thank you. Madam Chair, I want
to thank you for your commitment on this. I want to thank
Chairman Pallone, but also my Republican colleagues, certainly,
Mr. Guthrie and Cathy McMorris Rodgers, my seatmate, who I
can't be next to as we confer this morning. There is probably
not more an important issue on the health side than what we are
dealing with today. So I really appreciate this hearing, the
input of all the members as we work together to try and solve
these diseases that impact virtually every single family pretty
much every day.
And we need to move on and improve on what we were able to
do as a committee when I chaired it back in 2016 with 21st
Century Cures, when everyone, every member of this committee,
53 to nothing, supported that bill. And we now need to take
advantage of that time and what we have learned to move
forward.
So my staff reports that they have received legislative
feedback from both the majority and the minority. We--while I
have yet to actually sit down and look at the review since I
came back this week, we look forward in the coming days to
working with everybody to make sure that Cures 2.0 becomes law.
And I want to thank again everybody in the hard-working staffs.
Real-world evidence, there has been a little talk about
that earlier in some of the questions. We know that COVID has
taught this Congress a very valuable lesson. And when the chips
are down, the agency can work quickly and efficiently in
support of product approvals, as we saw.
We also know that real-world evidence, or as--we refer to
it as RWE--is going to help the agency improve its
decisionmaking. According to the FDA's own website they quote,
``This data holds potential to allow us to better design and
conduct clinical trials and studies in the healthcare setting
to answer the questions previously thought unfeasible.''
So for Dr. Allen with Friends of Cancer Research, Cures 2.0
includes provisions encouraging greater use of RWE to solve for
the medical product development and approval problems of today.
I would appreciate your thoughts on, one, whether we are
utilizing RWE appropriately as much as possible, and your
thoughts about the provisions as we--and Chairman DeGette and I
introduced 2.0 in that legislation.
Dr. Allen. Sure, and--well, thank you for the question. And
first and foremost, we wish you well in your recovery.
In terms of the utilization of real-world evidence, I think
Dr. Ram highlighted some important points, that there still are
methodological advancements that are needed in order to use
electronic health data regularly for causal inference around
the effect of a drug.
But I do think we also should note that the use of real-
world evidence is not necessarily a new concept. It has played
a very important role in things like monitoring for drug safety
and identification of adverse events, hopefully earlier, when
they can be mitigated, and well understood, and further
characterized through subsequent study.
And also in looking at generating evidence about
populations that weren't included in clinical trials, and there
is a very important role for real-world evidence in the
continued advancement of those methodologies to help augment
clinical studies and, actually, can help advance the goals of
many of the bills that are being considered today around
diversity and inclusion in clinical research.
Mr. Upton. Well, thank you.
Dr. Esham, I would like to just ask you quickly about the
PASTEUR Act, which, again, we included in Cures 2.0. It is
going to address, as you know, the problems of drug-resistant
bacteria and fungal infections by encouraging new drug
development.
This bipartisan bill--a separate bill, the FORWARD Act,
authored by Representatives McCarthy and Schweikert, would, in
addition, improve research in the FDA's focus on fungal drug
development.
If the goal of Congress was to prevent future pandemics
from happening, how would the PASTEUR Act help Congress achieve
them?
Dr. Esham. Thank you. So again, we are very supportive of
the provisions in the Cures that reinforces the importance of
PASTEUR.
As you know, this is one of the leading--antimicrobial
resistance is one of the leading causes of deaths globally.
Development for treatments for antimicrobial resistance do have
unique challenges. And we definitely urge enactment and passage
of PASTEUR this year to ensure that those policies are enacted
that will drive and sustain much-needed investment in this
space.
Mr. Upton. Well, thank you. And in my closing seconds I
would ask unanimous consent to enter into the record a letter
signed by over 100 entities calling for the swift passage of
the PASTEUR and FORWARD Act.
So with that, Madam Chair, I yield back the balance of my
time. Go Blue.
Ms. Eshoo. So ordered, so ordered.
[The information referred to appears at the conclusion of
the hearing.]
Ms. Eshoo. And please take careful care of yourself, you
are special to all of us, Fred. And we will see you soon. How
is that?
Mr. Upton. I hope so.
Ms. Eshoo. Great. OK, it is a pleasure to recognize the
gentlewoman from California, Ms. Matsui, for your 5 minutes.
Ms. Matsui. Thank you very much, Madam Chair. And I want to
thank the witnesses for being here today with us.
In recent years, Congress's work with the FDA, patients,
and stakeholders has spurred the development of robust and
meaningful patient experience data being submitted to the FDA
for review, including as part of new drug applications. And one
way to continue this momentum is to ensure there is clarity
around whether and how the FDA uses this patient experience
data.
To address this gap, I introduced the BENEFIT Act with
bipartisan support from my colleague on the Ways and Means
Committee, Representative Brad Wenstrup.
Importantly, I want to clarify that we are not proposing to
change the FDA review process, or ask how the patient
experience data influence a specific review decision. Rather,
the BENEFIT Act was simply to have FDA describe if they receive
patient experience data, and how it was incorporated in the
review process.
Dr. Esham, BIO has been supportive of elevating the patient
voice in the drug development process and, in fact, wrote a
white paper explicitly suggesting that patient experience data
be incorporated in the FDA benefit risk assessment, which my
bill would promote.
Now, FDA does currently indicate whether or not it received
submitted patient experience data. Dr. Esham, to your
knowledge, does FDA ever then indicate what they do with that
data? How might that insight be helpful to sponsors and patient
organizations? Dr. Esham?
Dr. Esham. Thank you, yes. And as you noted, you know, the
21st Century Cures Act, you know, required the FDA to make
public about when patient experience data was considered in the
approval of medicine. And over the years we have been working
very closely with patient groups to better ensure that that
information is more valuable and informative. And we do have a
white paper we would be happy to share with you and your
office.
We do think it is--it has been helpful, with the recent
publication that FDA published relating to the role of patient
experience data and benefit risk analysis, and how to collect
such information.
But we are supportive of your legislative efforts to
promote the inclusion of patient experience data in the benefit
risk assessment, and look forward to continuing to work with
you on this important issue.
Ms. Matsui. Thank you.
And Madam Chair, I would like to submit for the record a
stakeholder letter in support of H.R. 4472, as well as a BIO
white paper and a report commissioned by the FDA on the use of
patient--data.
Ms. Eshoo. So ordered.
[Material submitted for inclusion in the record follows:]
Ms. Matsui. Thank you. Accelerated approval can be a
critical tool for getting novel medication to market faster,
especially for rare disease patients who often lack access to
any FDA-approved treatment options.
Chairman Pallone's accelerated approval bill makes changes
to the timing and transparency protocols for post-approval
studies used to confirm a product's clinical benefit. Dr.
Ramachandran--I hope I didn't--I hope that----
Dr. Ramachandran. That is OK.
Ms. Matsui. OK. Why are these proposed reforms to
confirmatory trials beneficial for rare disease patients?
Dr. Ramachandran. Yes. Thank you so much, Congresswoman,
for the question.
You know, the proposed reforms within Chairman Pallone's
Accelerated Approval and Integrity Act are critical for rare
disease patients, one, to be able to show and demonstrate very
clearly that these drugs that are being approved much more
quickly and made available to patients much more quickly are
actually truly clinically beneficial.
You know, a lot of the statements have been around speed,
and how quickly, you know, these drugs are coming to market,
how quickly they are getting converted to traditional approval.
And when we actually looked at the data to see how long these
trials take to actually show any sort of result, they only take
about 17 months. So the provisions within Chairman Pallone's
bill to have automatic expiration after 1 year or 5 years after
a drug has come to market are perfectly reasonable, and kind of
give even more ample time for manufacturers to meet these
requirements.
But mostly for me, as a clinician, I just want to know for
sure that the drug actually works, and these post-approval
studies without adequate oversight won't show that unless the
FDA is keeping an eye on them.
Ms. Matsui. Sure. Absolutely. Well, thank you so much.
Now, last, I have heard concerns that the accelerated
approvals will automatically expire in the middle of clinical
trials if we pass the Accelerated Approval Integrity Act. But
as I understand the bill, this Acts as a backstop, and FDA will
allow clinical trials to continue beyond five years if they are
making adequate progress. Dr. Ramachandran, is this correct
doesAccelerated Approval Integrity Act build in this
flexibility?
Dr. Ramachandran. Yes. The flexibility that is built in is
really for the FDA to, you know, understand that, you know,
different drugs and different diseases might require different
periods of time. And so, as a part of the bill, the FDA does
negotiate with the sponsor, and does discuss with them what a
appropriate completion date would be for those post-approval
studies.
And hopefully, you know, that builds in that FDA
flexibility to be able to say, OK, a trial might take longer
than the 5-years, that we have the automatic expiration, and
the sponsor can continue to engage with the FDA to not have the
drug withdrawn if it is in the middle of a trial.
Ms. Matsui. Well, thank you so much. I appreciate the
clarification, and I yield back.
Ms. Eshoo. The gentlewoman yields back. It is a pleasure to
recognize the gentleman from Virginia, Mr. Griffith, for your 5
minutes of questions.
Mr. Griffith. Thank you very much, Madam Chairman. I
appreciate it. Let me dovetail a little bit with Representative
Matsui.
We had a discussion last week during the user fee hearing--
I--sorry, February 3d, last month, related to risk evaluation
and mitigation strategies for clozapine and another drug that--
its name is hard for me to pronounce. And I just want to make
sure, Madam Chair, that we are working on this issue. Dr.
Joyce, Representative Matsui, Barragan, and I are all working
on some legislation we hope to have coming out that will help
on this.
But as you will recall, we learned that physicians,
pharmacists, and patients lost access to the REMS platforms for
these drugs when new platforms were launched late last year.
And our legislation is intended to provide more accountability
and transparency so the patient doesn't find themself suddenly
without the medicine that they have relied on and need. So I
will leave that part at that point, but I did want to dovetail
with Representative Matsui and her work on those areas.
Ms. Eshoo. So noted.
Mr. Griffith. Thank you.
Mr. Gaugh, I want to thank you for your written testimony
and your support of the INSPECTIONS Act, which is H.R. 7006,
which Mr. Welch and I introduced in an effort to improve FDA's
inspections of foreign drug manufacturing establishments. This
committee has heard many stories, some of them, frankly,
horrific, about the conditions and the shortfalls of our--the
conditions in foreign labs or foreign medicine-producing
facilities, and our shortfalls of current inspection processes.
And it is time that we start addressing them.
You say in your written testimony that my bill could be
strengthened--and that is always a good thing, you always want
to learn what you can do better--with additional provisions on
the use of alternatives to in-person inspections. And I would
first like to clarify. You say the FDA should be required to
evaluate these tools when an in-person inspection is not
possible, but then go on to describe a situation in which an
in-person inspection does occur.
In the first instance, are you describing a situation in
which an in-person inspection may be temporarily impossible,
but later resolved?
Mr. Gaugh. Yes, that is correct.
Mr. Griffith. OK, and I suspected that was the case.
The GAO report required by the bill that Mr. Welch and I
put in would require a thorough description of all the
alternative tools, including remote inspections other trusted
countries are utilizing to facilitate inspections of foreign
establishments. Could you briefly describe to the folks at home
how a remote inspection works?
Mr. Gaugh. So remote inspection--and it is not an
inspection, it is an evaluation. So as the FDA has very
eloquently said, it is a remote evaluation, RIE. And what they
do is a virtual inspection, if you will, but it is not
inspection. Based on the legislation, and how the legislation
in 704 is written, it can't be an inspection, but it still does
virtually the same thing.
In fact, there was just an article in Pink Sheet this week
that talked about--that the FDA talked about how they are doing
these inspections. They want to make sure that the facilities
have the right equipment, so they can walk around with an iPad
or a very high-level iPhone to be able to look at the different
areas that they are inspecting. So they will have the papers in
front of them, the FDA will, at their desk. Then they want to
do a walk-around to see if the SOPs that they are reading and
the actions are equal.
Mr. Griffith. And that equipment is paid for by the
manufacturing facility, is it not? The smartphone or the
laptop.
Mr. Gaugh. Yes.
Mr. Griffith. Yes. And you know, I have just got to say,
obviously, somebody live and in person is going to be better.
But when we don't have enough inspectors--and we are already
way behind in inspecting some of these facilities, whether they
be in Europe or particularly in Asia--this is better than
nothing.
I mean, we heard testimony in one of the inspections that
they actually found feces on the walls in the areas where they
were manufacturing medicines that we are taking. And so at
least this would show that. And even if they cleaned it up just
for that day, that is better than not having anybody there.
Isn't that true?
Mr. Gaugh. That is correct, yes. So it is not as good as
in-person, because you may only see three of the four walls,
for example, and the fourth is the one you are concerned about.
But in today's world, where we are not able to inspect, or the
FDA says they are not able to inspect, we need to have another
tool, and this is a very viable tool.
Mr. Griffith. I appreciate it very much, thank you.
Dr. Esham, you were talking earlier, and you got into
resistant microbials to our antibiotics, and I am sure you all
are looking into it. And I would encourage everybody to take a
look at ``The Perfect Predator.'' It is a book that I read
about a year-and-a-half ago, and it is by Steffanie Strathdee
and Thomas Patterson. And it is about--it is actually a love
story with medical science all thrown into it. It is a great
read, but it talks about phage therapy, and what we ought to be
doing, and where we ought to be going. And I think that is a
great tool for us in the future. Would you agree, yes or no?
Dr. Esham. Yes, and I am excited to have a new book to
read.
[Laughter.]
Mr. Griffith. There you go. I yield back.
Ms. Eshoo. A good answer. It is a pleasure to have her
right here in the chamber, the gentlewoman from Florida, Ms.
Castor, for your 5 minutes.
Ms. Castor. Well, thank you, Chair Eshoo, for calling this
very important hearing. And thank you to all the witnesses for
being here today.
As we discuss innovation in medicine, it is critical that
innovation is accessible to all. And many of the bills being
considered today address diversity and equity in the
biopharmaceutical development process, and I look forward to
working with The Chair to enact them.
However, there is an important population that also must be
considered in any effort to advance innovation, and that is
pregnant and lactating people. Each year in the U.S., six
million women become pregnant, and more than three million
initiate breastfeeding. Almost 90 percent of women in the U.S.
will give birth during their lifetime. And despite how common
it is, and how important, how critical that time of pregnancy
and postpartum is to development of mothers and--for mothers
and the development of babies, there is very little information
on the safety of therapeutics and vaccines in pregnancy, and
even less on safety for the baby while breastfeeding.
And we saw this failure most recently during COVID-19, with
the vaccine there, where developers originally chose to exclude
pregnant people from their trials, leading many pregnant
people, who are at higher risk for severe illness or death, to
forgo protection of the vaccines. So we can't let the status
quo persist.
I was proud to sponsor legislation that was included in the
21st Century Cures Act that created the PRGLAC Task Force,
which issued 15 recommendations and a detailed implementation
plan to ensure we protect pregnant and lactating people through
research, not from it. And I am working now on followup
legislation to advance many of these recommendations.
So, Dr. Esham, many of the PRGLAC recommendations focus on
enhancing post-market surveillance for the therapies and
vaccines in pregnancy. And I was encouraged to see a section on
pregnancy safety in the PDUFA commitment letter. Can you
explain why current pregnant safety surveillance systems
haven't produced robust data, and describe the opportunities to
strengthen pregnancy registries and other post-market studies
for pregnant and lactating people?
Dr. Esham. Well, I think you actually very eloquently laid
out that--some of the issues that we were trying to resolve
through the PDUFA 7 agreement. Again, as you stated, there is a
section in there to really try to advance how--you know, to
require FDA to develop a framework describing how data from
different types of post-market pregnancy safety studies might
optimally be used.
So again, we think that the provisions in PDUFA 7 will be
very helpful, and I am happy to discuss that with you in
detail.
Ms. Castor. Great. Dr. Ramachandran, experts advise that we
need focused research to assess the risks of medications to
expectant mothers and babies. How does industry and the
research community approach inclusion of these populations in
clinical trials and research?
And what more can trial sponsors do to ensure pregnant and
lactating people are represented in clinical trials?
And would clearer guidance from the FDA, with more specific
recommendations for trial sponsors on the inclusion of these
populations be helpful?
And what other steps do you think we should take?
Dr. Ramachandran. Yes. Thank you so much for this question.
This is a question that is very near and dear to me. I am
actually a family medicine physician by training. I take care
of babies, kids, pregnant women, and older adults. So it is a
question that has come up routinely, especially when talking
about COVID-19 vaccines. I was actually breastfeeding when I
received my vaccination, so it was a key consideration for me,
as well.
You know, currently, clinical trials or industry sponsors
tend to not include pregnant or lactating women as a part of
the studies. Part of this is in trying to include populations
that are healthier, that are populations without comorbidities
or any other underlying conditions to be able to better tailor
results to be positive. And that has been an unfortunate
consequence in terms of FDA oversight on inclusion and
exclusion criteria.
However, I am, you know, reassured that, because of your
legislation and with what is included PDUFA 7, that there will
be more post-marketing surveillance, and more opportunities for
registries, observational data of pregnant women, so that we
can be able--pregnant and lactating women--so we can be able to
know what the effects are on those populations.
But definitely, clear FDA guidance on this issue is
critically important, and this is an area in particular where
FDA could actually put out guidance regarding real-world
evidence in the post-marketing surveillance phase, in
particular, for these populations. That would be very
beneficial for us, as practicing clinicians, to be able to
offer guidance for our patients.
Ms. Castor. Thank you very much.
Thank you very much, Madam Chair, and I will yield back my
time.
Ms. Eshoo. The gentlewoman yields back. The gentleman from
Florida, Mr. Bilirakis.
There you are.
Mr. Bilirakis. Thank you.
Ms. Eshoo. You are recognized for your 5 minutes.
Mr. Bilirakis. Thank you, Madam Chair----
Ms. Eshoo. Good to see you.
Mr. Bilirakis [continuing]. I appreciate it very much, and
I want to thank the witnesses for----
Ms. Eshoo. And his father--for those that may not know
this, Mr. Bilirakis's father at one time was the chairman of
this subcommittee, a wonderful chairman.
Mr. Bilirakis. Yes, yes, ten years. Ten years, yes. Thank
you very much for bringing that up. He is doing great. Thank
you.
I am particularly grateful to see my bill, Madam Chair, and
I appreciate you putting it on the agenda today among the 22
bills. I co-lead this bill with the caucus chair,
Representative Butterfield, the Rare Disease Caucus, and it is
called the Speeding Therapy Access Today Act, the STAT Act,
H.R. 1730 on the docket today. And I am hopeful The Chair will
continue to work with us, and I know she will, on this
bipartisan bill to consider it as part of our user fee package.
I know there are no guarantees.
I have said before rare diseases are not a rare problem,
and they affect almost 1 in 10 people in our Nation. And while
we have made great strides and progress in the development of
therapies for certain rare diseases, we have a long way to go.
And there are particularly--particular challenges with these
small patient populations with up to 95 percent of rare
conditions that still do not have an approved treatment,
especially for ultra-rare diseases. We have got to do something
about that.
So Dr. Vereshchagina and Dr. Esham, can you share some
thoughts on why it is so difficult to develop treatments for
the rare disease in ultra-rare disease communities?
And what ways could cross-agency approach, that kind of an
approach at FDA, help solve some of the challenges you
described?
Dr. Vereshchagina. Thank you for this question. And as I
mentioned in PhRMA's opening statement, we recognize rare
disease drug development as an area that still requires a lot
of attention.
And as you mentioned, many patients still lack FDA-approved
treatments. So there is a lot of challenges stemming from the
fact that patient populations are very small, and it might be
challenging to recruit patients into clinical trials. And this
becomes even more of a concern for ultra-rare diseases, where
patient populations can be, you know, literally, in dozens or
even less.
And because of small patient populations, there is also a
challenge of, you know, sometimes natural history of disease is
not known. Today already many people mentioned maybe there are
not established endpoints.
So this is why we supported rare disease drug development
provisions in PDUFA, both the current cycle and the upcoming
PDUFA 7 cycle. It includes dedicated pilot to work on
establishing and finding those endpoints for disease drug
development.
It also includes provisions specifically supporting FDA's
task forces in both drug center, CDER, and biologics center,
CBER. So a sponsor will be able to continue working with FDA
very closely on solving those underlying clinical trial design
and endpoints issues.
Mr. Bilirakis. Thank you.
Dr. Esham, do you have anything briefly to add, please?
Dr. Esham. I think she stated it very well. Again, these
are issues that--the challenge is compounded by often working
where there is little precedence. This is innovation in its
truest form.
You know, as you know, there is--thousands of diseases
still don't have a treatment available, and there is thousands
more diagnosed every year. So again, we need to foster
development pathways for the treatments of these diseases,
particularly for those patients that have no options.
So we would love to continue to work with you on these----
Mr. Bilirakis. Thank you.
Dr. Esham [continuing]. Important issues.
Mr. Bilirakis. Thank you so much. I appreciate it.
Dr. Vereshchagina--I practiced this, but it is very
difficult; I have a tough name, as well--so your testimony also
specifically mentioned the need to preserve incentives for rare
disease drug development, such as those under the Orphan Drug
Act, for continued research and development investments. I
couldn't agree more.
I truly believe that the STAT Act will continue to enhance
those incentives by bringing in additional cooperation and
expertise within the FDA to treat rare conditions, such as
advancements in trial design, statistical analysis, and
regulatory science.
Can you explain how new incentives and tools at FDA could
work to help bring rare disease products to market faster?
Dr. Vereshchagina. Yes. Thank you for this question. So the
Orphan Drug Act demonstrated that it has been tremendously
helpful for companies to provide that needed incentive to go
into the area of a lot of uncertainty. And maybe there is--
where, again, there is not enough scientific data available,
and the basis. So companies do need those incentives and
regulatory predictability to go into those areas and develop
much-needed drugs for rare diseases.
And while I can't specifically comment on the STAT Act,
PrRMA and our member companies do support incentives for rare
disease drug development.
Mr. Bilirakis. Thank you very much.
I yield back, Madam Chair. Thank you.
Ms. Eshoo. The gentleman yields back. The Chair is pleased
to recognize the gentleman from Maryland, Mr. Sarbanes, for
your 5 minutes questions.
Mr. Sarbanes. Madam Chair, thank you very much for the
hearing today, and I want to thank our witnesses, for sure.
The purpose of the hearing is to discuss how we streamline
the development and approval process for drugs and
therapeutics, as well as how to strengthen program integrity,
with the goal of ultimately getting people across the country
the medication and therapies they need to live long and healthy
lives. Obviously, we have got a number of different proposals
that are on the table and in front of us today.
Accomplishing this broad goal will not be a small feat. We
know that. In order to achieve important biomedical
breakthroughs that will make this goal a reality, we need to
diversify the kinds of research being conducted in the field of
biomedicine. Many people have spoken to that.
A critical component of this, I think, is to make sure that
we are supporting early career researchers. We know that
competition for Federal research dollars is fierce, and NIH can
only support a certain percentage of the projects that it
believes are qualified for funding. So it is a tough
environment, competitive environment.
Early career researchers who have not yet had a chance to
establish a track record of research success are, obviously, at
a disadvantage when competing with their more established peers
for these limited funds. This means that we may not only miss
out on important and perhaps novel research that may--that they
may choose to pursue, but also face an inadequate pipeline of
experienced researchers to fill the void where more
established--when more established researchers retire.
Dr. Mesa, can you speak to the specific benefits that
funding early career researchers can bring in this space?
Dr. Mesa. Thank you very much for the question. It really
is a critical piece.
As a cancer center director, part of my role is helping
develop folks, really, from the high school level all the way
through junior faculty to pursue careers in cancer, and to make
a difference. You know, and the ability to be able to support
them is critical, both with Federal programs as well as a
variety of innovative approaches that are being taken with
everything from colleagues in the pharmaceutical industry to
independent foundations.
But it really is critical. They have to have that initial
opportunity to be able to bring their talents to the critical
questions that we have heard today in front of the committee.
Whether it be rare diseases, cancer, or diversity, we need that
intellectual firepower working on our behalf.
Mr. Sarbanes. Another way--thank you very much, I
appreciate for that (sic). Another way to diversify biomedical
research, if this makes sense, is to cultivate more diversity
among the scientists that are conducting that research. And
according to the National Science Board's Vision 2030 Report,
which discusses what the United States should do to stay a
global leader in innovation, women and minorities continue to
be under-represented in science and engineering.
Again, to you, Dr. Mesa, what steps can be taken to help
increase diversity among researchers in the field of biomedical
research?
Dr. Mesa. It truly is about every stage of the pipeline.
So at our university it even begins at the high school
level, really trying to develop healthcare careers, and have
pipelines that then lead through the undergraduate level,
graduate programs, and really programs to be able to establish
them as junior faculty. So the development along the whole
pipeline is really critical.
If it is just at the junior faculty level, we probably
don't have the diversity yet. As an NCI-designated cancer
center, we now all have been asked, very appropriately, to have
diversity, equity, and inclusion plans in place for our centers
to really try to develop both our workforce and our leadership
for the future.
Mr. Sarbanes. Thank you. And of course, we know, you know,
these diversity initiatives, wherever they exist, can either
become just sort of box-checking exercises, or they can become
a sort of leading, vibrant edge of whatever the organization
is. And that is, obviously, what we are looking for in the
research space.
Dr. Esham, I would like to turn to you briefly on these two
questions: What role can industry play in supporting early
career researchers and increasing the diversity of biomedical
researchers?
Dr. Esham. Thank you. I think we do have the opportunity to
play a role. And again, I think, as mentioned, we often try to
and are continuing to establish collaborations to communicate
at the earliest levels what the possibilities are in having a
scientific and health-driven career.
We work with many of our State affiliates that engage with
high schools, middle schools. Many of our companies often
engage with high schools and middle schools to--again, it is
about showing the opportunity.
You know, I could speak--I grew up at a small town in
Kentucky, and I myself was not aware of these opportunities. I
sort of accidentally--and thankfully--stumbled into many of
them.
But providing children of all races and genders the ability
to properly assess what their opportunities really are is quite
important.
Mr. Sarbanes. Thank you very much.
I yield back, Madam Chair.
Ms. Eshoo. The gentleman yields back. The Chair is pleased
to recognize the gentleman from Florida, Dr. Dunn, for your 5
minutes of question, sir.
Mr. Dunn. Thank you. Thank you very much, Madam Chair and
Ranking Member Guthrie, for hosting this hearing today to
discuss legislation that may very well impact development of
future cures.
As we consider the policy that may accompany the user fee
agreements this year, it is important to strike a balance
between the FDA giving it the regulatory tools it needs to
ensure quality and safety, while still guaranteeing that the
agency doesn't get in the way of the American innovation that
we are all so proud of.
Congress must also continue to work to ensure that patients
have access to those medications soon after they are approved.
And this involves some forward-thinking, accelerated approval
processes such as Ranking Member Rodgers's Accelerating Access
for Patients Act, which I intend to support.
I also want to convey my support for H.R. 1730, introduced
by Representatives Bilirakis and Butterfield, which aims to
move the needle on rare diseases; and H.R. 4511, introduced by
Dr. Burgess to, importantly, bring real-world evidence into the
review process.
Another component of guaranteeing access to patients is
supporting the development of generics and biosimilars,
specifically the interchangeable biosimilars, which should be
more affordable and, therefore, more easily accessed by
patients.
When the FDA testified in front of this committee last
month, I asked about their willingness to provide the drug
sponsors with comprehensive FDA review documents in the event
they hand down a Complete Response Letter to an applicant. The
FDA answered that this requirement would have a chilling effect
on the review process. Frankly, that answer frustrates me.
As we all know, new drug sponsors spend years and years,
tens of millions of dollars to develop a single cure, and often
they fail along the way. So when an innovator finally does file
for FDA approval, meets the FDA's surrogate endpoints, and
their product has no evidence safety concerns, and then still
receives a Complete Response Letter, I believe they should be
granted access to the comprehensive review documents that went
into that decision. This type of transparency would help them
remedy any deficiency, and would also provide certainty to the
investors. And this is really important for a lot of small and
mid-sized biotech companies who find themselves in this
position, and then are forced to actually shut down because of
that.
So to that end, Dr. Esham, a recent report from Pink Sheet
detailed an uptick in the issuance of CRLs compared to previous
years. Could you speak to the issue of Complete Response
Letters lacking comprehensive information about application
deficiencies, and how does that hurt you?
Dr. Esham. Thank you for that question. And I have read the
article.
I will say, in conversations with our member companies, it
is important that when--it is critical, when receiving a CRL,
that the information provided clearly defines what the issues
or deficiencies were that led to that decision. Without that
information, it is very difficult to determine whether those
hurdles can be overcome and investment is warranted to conduct
additional studies or not.
And the problem is not whether treatment fails because it
did not meet regulatory standards to support approval. It is
whether the development is halted of a treatment that may
provide benefits that we want to avoid.
Mr. Dunn. Yes, so I am not surprised to hear that. Thank
you very much.
Dr. Vereshchagina, the--how does a sponsor, drug sponsor,
approach their decisionmaking after a CRL is issued and calls
for new clinical trials, despite hitting previously agreed-upon
endpoints?
Dr. Vereshchagina. Thank you----
Mr. Dunn. So you know that happens, right?
Dr. Vereshchagina. Yes, and I think the most important
thing highlight here is the open communication between sponsors
and FDA that Complete Response Letters are not surprised. And
this is, for example, why user fee agreements include specific
opportunities and multiple points during the drug development
that requires FDA and sponsors get together and discuss this
issue.
So it does not actually get to the point of the Complete
Response Letter because, as you said, it may impact clinical
development. But the goal is really to make sure that there is
very clear understanding on both sides what is required for the
timely approval, and that sponsors and FDA is together
working----
Mr. Dunn. So being--my time is--I am going to say to sum
up, it sounds like you two are in agreement that clearer
communication between the drug sponsors and the FDA throughout
the process, including at the time of the CRL, but before that
as well, it would be imperative to actually help us innovate
and create new drugs for Americans.
So thank you very much, Madam Chair. I yield back.
Ms. Eshoo. The gentleman yields back. It is a pleasure to
recognize the gentleman from Oregon, Mr. Schrader, who has been
participating, sitting here, and listening, and has been very
patient.
You have your 5 minutes now.
Mr. Schrader. Thank you, Madam Chair, I appreciate it. I
would like to thank everybody for being here for the
conversation, very important conversation on innovation and
ability to improve getting medications, lifesaving devices to
the marketplace. I would like to discuss my biosimilar
interchangeability bill.
When the--when we all worked on the Biologic Price
Competition Innovation Act, we laid out a process, set a pretty
high bar for interchangeability, given the relative newness of
the--of these products. And for that accomplishment we set a
finite amount of exclusivity for the first such interchangeable
biosimilar with a single biologic reference product.
Unfortunately, since that time, FDA has changed the
original intent of the Act, and interpreted it so that a
component of determining the eligibility, the strength of two
products, to mean the same exact content with the same exact
concentration of the biosimilar. Sometimes that is important,
but in many cases it is not.
For example, within the current interpretation, a half mil
of an active ingredient as formulated in a one mil solution is
considered lower concentration, compared to a half mil in a
1.75 mil solution. Both contain the exact same amount of active
ingredient, slightly different levels of inactive saline, but
the latter is considered high concentration based on the ratio.
No clinical difference in the outcome of that product.
What happens under that scenario is that the reference
product sponsor can block biosimilar--generic, if you will--
competition by making clinically insignificant changes to
product concentration. That was never the intent. The goal was
to get biosimilars, you know, generics to marketplace as
quickly as possible, and reward innovation, reward actual
innovation.
I am floored by the assumption that some in the industry
seem to think that making that exclusive change, you know, for
different concentrations would be a legitimate exercise. It
goes against everything Congress has stood for, myself in
particular, trying to get generics to marketplace.
So I guess a question. Dr. Gaugh, I go to you. Has the FDA
awarded exclusivity for interchangeability on two different
biosimilars for different concentrations? Where are we with
that?
Mr. Gaugh. Yes, they have done that. That is correct.
Mr. Schrader. And what has been the effect of that, in your
opinion, with regard to the ability to bring different generic
products, different biosimilars to the marketplace?
Mr. Gaugh. Thanks for the question, and thanks for the bill
that you put forward.
We totally support the concept of where you are going with
this bill. The concern is we think it may have some unintended
consequences on really opening back up BPCIA completely, and
could lead to some other exclusivity issues that might occur.
So we would like to have the opportunity to work with you
to maybe tweak this a little bit further, because there is
still that exclusivity period that we are concerned about.
Mr. Schrader. Yes, we definitely want to protect that
exclusivity period for those folks that are bringing it in. I
would be glad to work with you on that. And that is part of the
reason we still have the waiver ability for FDA, to make sure
that--because sometimes--I am a veterinarian in the real world,
and concentration does matter in some cases, and so we need to
have a little leeway with the FDA to be able to pursue that.
Second question, I guess it would be for Dr. Esham. I am
also very interested in the FDA Modernization Act. I think that
has some great opportunities out there. As a veterinarian, you
know, any testing that can be done without the use of our four-
footed animal friends, I think, is to our advantage, and
certainly to their advantage.
Precision medicine, using tissue cultures and some of the
advanced techniques that I think we are looking at here in the
21st century is pretty darn exciting. I wish we had that when I
was in active practice. However, I think it is also important
to recognize that, beyond tissue culture and, you know,
computer modeling, there are complex inner physiological
interactions within the animal and human body that need to be
taken into account.
So I just want to, you know, set people's concerns--or
allay people's concerns, hopefully. I am a fan of the
legislation. Is there any mandate in the legislation that FDA
must only use non-animal techniques and evaluations to
determine whether a drug is safe?
Yes, ma'am.
Dr. Esham. Oh, sorry. I will point out that we are still
reviewing this legislation, and definitely want to get back to
you and continue to work with you on this issue.
I will also State for the record that BIO is committed to
advancing tools and methodologies that can be alternates to
animal testing.
Mr. Schrader. Good.
Dr. Esham. We even have some peer-reviewed papers on
alternative approaches to non-human primates. So again, I am
happy to come in and have more detailed discussions with you.
Mr. Schrader. So how do you see that working out? I mean,
it is pretty exciting, having alternate models out there,
something the old model is based on what we did in the 1930's,
where we had no alternatives. So this offers, I think, some
pretty exciting new--how do you see that playing into, you
know, drug evaluation going forward?
Dr. Esham. I think we need to continue to advance it and
make it, you know, as much as we can, make it more--an approach
that can be used in drug development. Again, we are not in an
either/or situation, but we need to continue to advance these
alternatives.
Mr. Schrader. Very good. And I yield back. Thank you very
much.
Ms. Eshoo. The gentleman yields back. The Chair is pleased
to recognize the gentleman from Utah, Mr. Curtis, your 5
minutes of questions.
Mr. Curtis. Thank you, Madam Chair. Thank you, Mr. Ranking
Member. Thank you, witnesses.
I add my voice to that of my colleagues, which seems to be
a strong bipartisan theme that the policies that we are
considering alongside the user fees should ensure that the FDA
is functioning well and efficiently, and keeping up with the
vast needs.
It is imperative in Utah and, really, for all Americans
that timely access to safe and effective lifesaving medical
products is something that they can look forward to. I think,
if we can foster American innovation, and if the FDA can keep
up, we can do great things with the scientific advancements.
I have spoken at previous hearings about the importance of
FDA initiatives that advance the development and access to
treatments that fulfill unmet needs. I think, in this hearing
room, we have heard some passionate testimony from some of our
witnesses about the unmet needs, and how it impacts their
lives. I am proud of the bill that I helped champion, and it is
being considered today: the Equity in Neuroscience and
Alzheimer's Clinical Trials, ENACT, Act, which would encourage
the use of remote health technologies, such as remote patient
monitoring, to ease the burden of participation for many
communities.
My district in Utah--many people hear me talk about this a
lot--is very rural. I actually have 400 miles from top to
bottom, and I understand the amount of time people must spend
traveling to a clinical trial site creates significant
challenges. Geographic limitations should not impede progress
when there are technologies available that will help us
increase participation of unrepresented populations in clinical
trials. As technology advances, I believe we will continue to
find ways to utilize such advancements to improve our
healthcare system and the medical products on the market.
I think one place we can do this is how we provide
pharmacists and physicians with prescribing information. One
option we should consider to do this is electronic billing. Dr.
Vereshchagina--we have all tried to pronounce that, and I
appreciate your patience with us--you highlighted the
importance of digital health technologies. Can you tell us what
role you believe electronic labeling plays in ensuring
physicians and pharmacists have the most up-to-date prescribing
information?
Dr. Vereshchagina. Thank you for this question, and thank
you for recognizing the value that digital technologies can
bring to both drug development, but also to healthcare.
As the response to COVID-19 pandemic indicate that there is
tremendous potential in both collecting data, analyzing data,
sharing data electronically, both in clinical trials and in
patient care settings. So that is an area that
biopharmaceutical industry and our member companies are
definitely very interested in, excited, and supportive. And we
included specific provisions in PDUFA 7 agreement to make sure
that we continue to develop methodologies, and that data is
being able to be collected and analyzed and used for regulatory
decisionmaking.
Mr. Curtis. Thank you.
Still on the topic of digital health technologies, Dr.
Esham, I saw you nod your head when I was talking about these
distances, dealing with participation in clinical trials. Could
increasing remote health technologies in clinical trials
support expediting trials' responsibility and certain
solutions, and what should we be looking at in that area?
Dr. Esham. Absolutely. We do believe that the use of
telehealth and other digital technologies can reduce patient
burdens generally, and also break down some of those
prohibitive geographical barriers by lessening the amount of
time a patient needs to visit a clinic in person that requires
taking off work, finding child care.
These technologies also enable the ability to capture data
in a less obtrusive manner, and in a more continuous manner,
and enable staff to potentially engage with patients more
effectively and also in a more timely manner.
So it does, can, and should play a significant role,
because we do believe it will make participation and can make
participation more manageable for patients.
Mr. Curtis. Thank you. Like my colleagues, and all of you,
I believe it is important to advocate for reduced out-of-pocket
costs for pharmaceutical drugs for our patients. One option to
consider is the low of--is the role of low-cost, generic, and
biosimilar medicines in our pharmaceutical market.
That said, we should also be mindful that it is not FDA's
job or place, or even legal for them to set these prices. Dr.
Gaugh, what role does FDA play in ensuring a competitive,
generic, and biosimilars marketplace that will ultimately drive
down the cost of these drugs for the American people?
Mr. Gaugh. I think the role they play is through what we
have accomplished in both GDUFA and BsUFA, and that is access
to the affordable drugs.
So through both user fee programs we have set up
milestones, if you will, and metrics that the FDA must meet for
the review of applications--not necessarily the approval, but
the review--within a 10-month timeframe. And we have also added
in GDUFA a 2-month add-on timeframe. If a product is determined
an imminent approval product, but something needs to be fixed,
something very slight, there is an additional two months that
is added in. So it turns into a 12-month clock, yes. But had
that not happened, it would have been a Complete Response
Letter, and would have gone into a second cycle, and it would
have been many months afterwards.
So it is really that timeline that we have improved from
years ago, when GDUFA didn't exist, at a 48 to 50-month time
point for approval to today, where we are at about a 27
average----
Mr. Curtis. Thank you. Yes, thank you. Thank you to our
witnesses.
Madam Chair, I yield my 13 seconds back.
Ms. Eshoo. There you go, thank you. Thank you very much,
Mr. Curtis. And I always take note that, no matter how long a
hearing is, you are here from beginning to end. And that says
everything about you and your attention.
And Morgan, who is getting up and leaving now, too.
[Laughter.]
Ms. Eshoo. And he didn't hear me, either. OK. Well, you
have to smile, right?
The Chair is very pleased to recognize the gentlewoman from
Illinois, Ms. Kelly, for your 5 minutes of questions.
Ms. Kelly. Thank you, Madam Chair and Ranking Member
Guthrie, for holding this very important hearing.
Madam Chair, I am glad that our bipartisan DEPICT Act has
been included, which will require the FDA to incorporate
accountability and enforcement mechanisms for clinical trial
diversity. However, real progress on clinical trial diversity
will require a multifaceted approach across Federal agencies.
Commitments from industry are simply not enough. We need to
do better for patients of diverse demographic backgrounds. We
need to have accountability for conducting clinical trials that
are reflective of the patients impacted by the disease or
condition.
Dr. Ramachandran, thank you for supporting the
accountability and enforcement mechanisms laid out in the
DEPICT Act to ensure clinical trial diversity. Would there be
any benefit to implementing similar accountability and
enforcement measures at the NIH, such as requiring the sponsors
that work with NIH to establish--I am sorrya clear measurable
diversity goals, and the funding application process, and have
these goals be enforced throughout the trial?
Dr. Ramachandran. Thank you, Congressman, for the question.
And yes, definitely, there would definitely be benefit for
NIH to set similar enrollment targets for sponsored trials or
funded trials from the NIH. There is a couple of reasons for
this.
The NIH is paying--playing an increasing role in funding
clinical trials, especially for a number of the novel gene
therapies that we are seeing coming to market, and particularly
those that are going to be effective or may be effective for
communities of color. You know, sickle cell disease, for
instance, there is a promising treatment that NIH is playing a
critical role in advancing. And so making sure that those
trials also include patients that are representative of the
patients who will be prescribed this is really important, not
just for the patients, but also for us, as clinicians.
The other part of this, too, is that, you know, as the
Nation's medical research agency, we would hope that the trials
that are funded by the NIH also reflect the Nation's
population. And so, you know, it is--I find it very critical.
And, you know, thank you for your leadership in terms of also
making sure that there is a whole-of-government approach in
terms of ensuring representation in clinical trials.
Ms. Kelly. Thank you. My dear colleague and friend,
Congressman Butterfield--who, yes, we will miss greatly--
mentioned about our bill, the Clinical Trial Diversity Act,
that will be introduced this month. And this would hold NIH-
funded clinical trial sponsors accountable for working toward
clinical trial diversity goals.
Diversity goals are not intended to be quotas. We do think
there needs to be an enforcement mechanism. Our bill would
empower NIH to use existing penalties, such as apply conditions
of funding continuation or, in extreme cases, terminate
funding.
Why is enforcement an important piece of holding clinical
trial sponsors accountable for diversifying clinical trial
participants?
Dr. Ramachandran. Yes, thank you for the followup question.
And, you know, this is critically important because, basically,
what isn't measured won't be managed.
So without NIH setting those sorts of targets, they are
not--there is not going to be movement from industry as we have
seen over the past, you know, decade in terms of FDA trying to
do non-enforceable measures to increase representation in
clinical trials, and really not moving anywhere in terms of
ensuring that more patients of color are being enrolled, and
even, you know, regarding older adults being enrolled in these
trials, as well.
On top of that, you know, NIH already does this to some
extent. It has great success in terms of setting enforcement
measures around clinical trials, particularly around clinical
trial registration and results reporting that has led to
industry sponsors paying attention, but also all trial sponsors
paying attention and actually adhering to those requirements.
And this benefits not only patients, but also, as clinicians,
to really know how these drugs and these devices will actually
affect our patients.
And with NIH playing such an important role in terms of
catalyzing, you know, truly transformative innovation, we also
want to make sure that they are being innovative in terms of
making sure that trials are representative of the Nation's
population.
Ms. Kelly. Thank you so much. And we are thrilled Doctors
for America has endorsed the Clinical Trial Diversity Act.
Dr. Mesa, would there be any benefit to requiring that NIH-
funded clinical trials implement alternative followups, such as
phone or telehealth alternatives, or increasing the
availability of night and weekend appointments?
Dr. Mesa. Yes. Without question, clinical trials really are
a critical aspect of how we care for difficult diseases,
including cancer. And certainly having both, you know, Federal,
as well as, you know, sponsored trials from the pharmaceutical
industry really try to make the trials as patient-centered as
possible is critical. So using new technologies, approaches,
expanded hours--really, think about what does it take to make
it feasible for the patient.
Ms. Kelly. Thank you so much. And I am pleased that
Leukemia and Lymphoma Society has endorsed the Clinical Trial
Diversity Act. This bipartisan bill, in conjunction with the
DEPICT and DIVERSE Act, would ensure that there is
accountability for clinical trial diversity, and that sponsors
have the tools to meet diversity enrollment goals.
Thank you so much, and I yield back.
Ms. Eshoo. The Chair now recognizes the gentleman from
Georgia, and he is coming in virtually for his 5 minutes of
questions.
Hi, Mr. Carter.
Mr. Carter. Thank you, Madam Chair.
Ms. Eshoo. How are you feeling?
Mr. Carter. I feel good. I feel good. Thank you for asking.
I am----
Ms. Eshoo. Good.
Mr. Carter. I am out----
Ms. Eshoo. I think we need to reset the clock, please.
Mr. Carter [continuing]. Some time soon.
Ms. Eshoo. OK, great. There is your 5 minutes.
Mr. Carter. Thank you, and thank all of you for being here,
the panel members. I want to talk real quickly about my
legislation, Enhanced Access to Affordable Medicines Act.
There was a recent GAO report that said that last-minute
brand labeling changes were a factor that could potentially
delay approval rates for generics. And, you know, approval
rates for generics is something that concerns me very much. We
give brand name drugs seven years for a patent. But, in
reality, that seven years is more like 10 or 12 years, because
it takes so long to get a generic to market. And I am trying to
do all that I can to speed that process up, so that we can get
generics to market as soon as possible.
Congress attempted to address this. We attempted to address
this problem in 2010, and--but there are still gaps in
implementation that have not been fixed with this problem.
The FDA has also stated that--working overtime to approve
generic medicines, but that issue still exists, as well.
My legislation, the Enhanced Access to Affordable Medicines
Act, would propose minor revisions to close the gaps to the
existing law, and it would prevent last-minute brand labeling
changes from further delaying generic entry.
Mr. Gaugh, I want to ask you. Are last-minute brand label
changes still a problem?
Mr. Gaugh. Thank you for the question. And yes, they are
still a problem. In 2020 alone, over a 6-month period, there
were 36 products that were delayed due to late label changes.
Mr. Carter. When this happens, does the FDA have a--does
the FDA have to review the updated labeling amendment, and that
is what significantly delays approval?
Mr. Gaugh. So the delay goes in a couple of different
directions.
First off, the brand company submits their label. The FDA
has to review it and approve it. Once they review and approve,
then the ANDA that is being reviewed cannot be approved until
that ANDA label has been changed to match what the brand
company just put in.
Your bill, which we support, will prevent that from
happening, giving the FDA the opportunity to go ahead and
approve. And then, within 60 days from the approval, the
generic company will make that label change. And of course, you
have the one caveat in there: if it is a warning change, then
that 60-day period would not happen, the approval could not
happen. So that protects the American public.
Mr. Carter. Good. Thank you, Mr. Gaugh. Thank you for that.
Now I want to talk about my Made in America Act. You know,
I have always said there is a difference in recognizing
something--or a difference in recognizing something and
realizing it. I think we have all known for some time that we
have got too many manufacturers, too many pharmaceutical
manufacturers, offshore, and we need to repatriate them and get
them back onshore. We realized that whenever this pandemic set
in, and whenever we realized just how dependent we were on
foreign countries for our pharmaceutical needs and for our PPE
needs, as well.
But one thing that this bill also addresses is the advanced
manufacturing that we are seeing a lot of now, and that is what
the Made in America Act tries to do. It creates an independent
pathway that is separate of drug products at FDA to access--to
assess these manufacturing processes.
Dr. Esham, I wanted to ask you, does the FDA currently--
does the FDA's current review process complicate bringing these
technologies to market?
Dr. Esham. I think we--well, to say that simply, we have
been seeking reforms, and some of that is reflected in the
provisions that we advocated for in the PDUFA 7 agreement to
require that the FDA--to get a commitment by the FDA to engage
the stakeholders and publish a strategy document outlining
specific actions they will take to facilitate the use of
advanced manufacturing technologies.
I will also note that we are supportive of the creation of
the pathway laid out in your legislation, and will note,
generally, that the reason we are--believe strongly in these
kinds of reforms is these technologies offer the ability to
optimize efficiency and promote scalable scalability.
Mr. Carter. Good, good. Thank you. Well, you all are great.
We need you on more panels. You all love my legislation, and
you are helping me here.
[Laughter.]
Mr. Carter. I am going to--Madam Chair, I am going to give
you back 19 seconds. Thank you.
Thank all of you all, I appreciate it, and I will yield
back.
Ms. Eshoo. Bravo. Where are you?
Mr. Carter. Bravo.
Ms. Eshoo. Are you--well, feel well soon, OK?
Mr. Carter. Thank you. Thank you.
Ms. Eshoo. Wonderful. All right. Dr. Ruiz of California,
you are recognized for 5 minutes.
Mr. Ruiz. Thank you for holding this important hearing, and
for including my bill, the Diverse Clinical Trials Act.
I am pleased that more and more attention is being paid to
equity in healthcare, and how to address the barriers that are
preventing it. As we have discussed in previous hearings in
this subcommittee, a lack of diversity in clinical trials is
one of those barriers, which is why I introduced the bipartisan
Diverse Clinical Trials Act with my fellow doctor and friend,
Dr. Bucshon.
This bill seeks to tackle this issue by reducing barriers
to participation in clinical trials by allowing researchers to
provide necessary equipment to participants, so they can
participate remotely or pay for ancillary costs of
participation, such as transportation to and from the site of
the trial. The bill helps ensure that more patients can
participate in trials, regardless of where they live or how
much money they make.
As a doctor who grew up in an under-resourced community,
practiced medicine in that community, and now represent the
largely under-served population, I understand the difference
that these flexibilities will make.
I also know the positive effects that increased diversity
will have on overall health outcomes. And isn't the whole point
to improve health outcomes for everyone?
It was my mission as a doctor, and it is my mission now, as
a Member of Congress.
Dr. Mesa, I hear from companies all the time that they want
to create greater diversity in their clinical trials, but they
have trouble doing so, even when the will is there. Can you
walk us through some of the barriers that researchers face in
creating a diverse clinical trial?
Dr. Mesa. So thank you for the question. And Representative
Ruiz, it sounds very much that where you grew up mirrors the
challenges that we face in south Texas.
You know, indeed, as we have reflected on these barriers,
they are multifold. And I am excited that, you know, many
aspects of the bill may help to address them.
You know, one, you know, how do we make it patient-
centered? You know, the technologies, the approaches that can
make it more feasible to participate, it will evolve. Right now
that is evolving as telemedicine. It may be other equipment to
facilitate that. It certainly requires some degree of ability
to potentially travel for sub-specialized care in a range of
ways. And it includes the other parts of, again, really having
it be an expectation, as opposed to just a hope.
Mr. Ruiz. Yes.
Dr. Mesa. So that, really, the trial is focused----
Mr. Ruiz. The awareness is also lacking of people knowing
that these trials exist, and that they can participate for them
(sic). Can you address for us what the real-world repercussions
are when you have a homogeneous clinical trial, and how that
can affect health outcomes?
Dr. Mesa. So it can be very clear that, if the trial
participants are homogeneous, we really might get the wrong
signal in terms of whether a drug is safe or effective. And it
may be either more or less safe or effective in any individual
group. So that diversity is critical for us to understand how
these drugs can be applied to the actual members of our
society, not just one sub-group.
Mr. Ruiz. You know, we--now let's talk about the non-
medical costs. So can you speak to the extent to which non-
medical costs, such as transportation and lodging, associated
with clinical participation can be barriers to patient
enrollment?
And could reducing these barriers also improve diversity?
Dr. Mesa. These are critical barriers, and trying to
overcome them is key. You know, these dollars add up very
quickly for transportation, lodging, and other pieces, and can
be a complete barrier for individuals that have insufficient
resources. So overcoming that is key.
One thing I would like, as I saw in the legislation, is
that they are--you know, removing them from the category of
being inducements. These are not inducements. These are really
just allowing feasibility of participation.
Mr. Ruiz. You know, we have heard a lot about health equity
and reducing health disparities. And yet too often track
records do not match up to the rhetoric. What can we do to help
ensure that companies walk the walk when they are conducting
their clinical trials?
Dr. Mesa. I do think the proposed language that really
expects minority accrual plans to really be reflective of the
demographics, you know, both of the national population, but
also mindful of the disease, as well.
You know, there are certain diseases where we have over-
represented groups such as African American men with proState
cancer or others. We need to be certain that there really is
sufficient sampling of these groups that are very disease-
specific----
Mr. Ruiz. Or in Hispanics, non-Hispanic steatosis, fatty
livers, et cetera. That is predominantly in Hispanics, as well,
as well as diabetes.
Look, as a doctor, when we provide clinical care and we
look at the evidence, we look at the sample of the individuals
that were studied, and there is two big things that we want to
look at--one, randomization; and two, demographics--to ensure
that our prescriptions are going to work for our patients. And
if the sample does not reflect our patient population, then we
cannot say with absolute certainty that those--that study
reflects the care for that patient.
Thank you. I yield back.
Ms. Eshoo. The gentleman yields back. The Chair is pleased
to recognize the gentlewoman from California, Ms. Barragan, for
your 5 minutes of questions.
Ms. Barragan. Thank you, Madam Chairwoman, for holding this
hearing today to discuss how Congress can help streamline
development and approval processes for drugs and therapeutics,
strengthening research integrity, and improve diversity and
equity in clinical trials.
Speaking of clinical trials, I continue to be concerned
with CMS's proposed national non-coverage determination, which
severely restricts Medicare beneficiaries' access to an entire
class of Alzheimer's drugs. To only provide coverage to only
those enrolling in CMS-approved clinical trials means that only
a privileged few can participate, further exacerbating health
inequities for low-income people and people of color.
There is a staggering amount of work left to do for
patients with unmet needs, especially for patients with
Alzheimer's disease and other rare and serious diseases.
Patients suffering from these diseases are depending on us to
preserve and protect the accelerated approval pathway.
Dr. Allen, my first question is for you. The accelerated
approval pathway has been successful in ensuring access to new,
safe, and effective drugs for patients most in need of new
treatments. This has been particularly true in oncology, where
treatments receiving accelerated approval were made available a
median of 3.4 years earlier than would have been possible under
the traditional FDA approval pathway. Many patients suffering
from neurological disorders, like Alzheimer's and Parkinson's
disease that lack adequate treatments, are wondering if this
level of success can be replicated for their own condition or
their loved ones' condition.
My question is, how can the accelerated approval pathway be
optimized to help bring promising treatments to patients
suffering from neurological disorders and rare diseases, while
ensuring their--they are safe and effective, and what would be
the consequences of limiting the accelerated approval?
Dr. Allen. Thank you very much for the question. You know,
I think that, hopefully, the experience in oncology that has
been shown about the success of the accelerated approval can be
an example of how to extrapolate it to other therapeutic areas.
I briefly mentioned this, but one of the reasons that this
has been so successful in oncology is not necessarily an FDA
issue alone. It was one that the cancer research community
really came together to pioneer and standardize some of these
endpoints, so that they could be well understood, easily
applied, and then sufficiently followed up on over time. And I
think that is a key reason why we have seen so much success in
oncology.
So in thinking about what it would take in order for
accelerated approval to be more readily applied to other
therapeutic areas like those that you have mentioned, I think
it will be a large research infrastructure collaborative
endeavor in order to identify and validate those endpoints, in
order to make the accelerations that we have seen in oncology
available in other therapeutic areas.
Ms. Barragan. What do you think the consequences are for
limiting the use of accelerated approval?
Dr. Allen. I am sorry, can you repeat that?
Ms. Barragan. The consequences of limiting the use of
accelerated approvals.
Dr. Allen. If accelerated approvals are inappropriately
limited, I think you will see delays in access, certainly.
But I think we also have to be conscious that the hallmark
of the accelerated approval process is balancing uncertainties.
And so what is made possible by the validation of surrogate
endpoints is a shift in those uncertainties.
I do think the legislations that are being proposed today
and being discussed into the future about strengthening that
post-market surveillance side of the equation will help reduce
those uncertainties over time, and ultimately help expand the
development of surrogate endpoints, knowing that there will be
a safety net of evidence in place for other therapies, too.
Ms. Barragan. Thank you.
Dr. Esham, while we have seen significant advances in brain
science, therapies for neurological disorders cost more to
develop and fail at a greater rate. For example, the Government
Accountability Office reported that, in recent years, FDA
reviewers denied more requests for and granted fewer
breakthrough therapy designations among neuroscience new drug
applications, or NDAs, than they did for any other disease
area. Could you discuss how a neuroscience center of excellence
at the FDA would increase patient access to safe and effective
treatments for neurological disorders and conditions?
Dr. Esham. I think we are still reviewing that legislation,
and are happy to have followup detailed conversations. But we
will--we concur with your picture about the problems that we
are not being as successful as we want to be in providing clear
pathways forward for the development of innovative treatments
for neurological diseases. So I am happy to followup with you.
Ms. Barragan. OK, thank you.
Madam Chairwoman, I yield back.
Ms. Eshoo. The gentlewoman yields back. The Chair is
pleased to recognize the gentleman from Texas, Mr. Crenshaw,
for your 5 minutes of questions.
Mr. Crenshaw. Thank you. Thank you, Madam Chair, thank you
to the ranking member for having this hearing. Thanks to all
the witnesses for being here, as well. And again, thank you,
Madam Chair, for--especially for your interest in stem cell
therapy, which I think is a very promising part of regenerative
medicine.
Ms. Eshoo. I am glad to work with you on it.
Mr. Crenshaw. Thank you. And as you know, I introduced a
bill recently with Dr. Burgess that would require some updates
to a 20-year-old regulation at FDA, specifically looking at the
definition of ``minimally manipulated,'' as--especially as it
relates to adipose stem cells. And I know we are not able to
consider it at this legislative hearing, but I absolutely
appreciate The Chair's willingness to work with me and my
office on including it in the final bill.
The FDA has been able to do a lot for innovative medicine,
but hasn't been able to move forward with novel approaches to
regenerative medicine--not just curing diseases, but renewing
and replacing parts of the body that are diseased or no longer
working.
Many of our regenerative medicine projects are working on
ways to renew and replace cardiac, liver, lung, muscle, and
even ocular tissue. To oversee these treatments, the FDA has
relied upon a regulation that was written in 1997 and finalized
in 2001, which is, of course, what we are looking at asking the
FDA to possibly reform.
Dr. Mesa, this is for you, because it is my understanding
that one of the treatments for leukemia, which you specialize
in, can be autologous or allogeneic stem cell transplants
derived from bone marrow. And so I am wondering if you have
input and--you know, onto these potential reforms to this 20-
year regulation, and maybe what safeguards we should be mindful
of as the FDA looks at that.
Dr. Mesa. You know, without question, the ability to use
cellular therapy has had an enormous impact on cancer. You
know, continuing to modernize the regulation to expand that is
well worthwhile.
You know, autologous and allogeneic transplant have had a
huge impact on bone marrow disorders. And we continue to evolve
now to cellular-based therapies, you know, that are leveraging
the immune system in a range of ways. So I am certainly
strongly supportive of that evolution to allow these
technologies to continue to evolve, to really expand how
therapies can impact cancer and other diseases.
Mr. Crenshaw. OK, thank you. And what was the FDA worried
about in stem cell therapies in 2001 that maybe they don't need
to be worried about today?
How has the science changed to allow more access to
regenerative medicine?
Dr. Mesa. I think the ability to really, you know, utilize,
you know, more differentiated cells, or take more
differentiated cells, indeed, differentiate them to utilize
them, you know, there--certainly, there was always the concern
in terms of, you know, in--derived cells, in terms of the
initial piece. But now, with the ability to really leverage
cells further on, it really is pushing regenerative medicine
in, you know, many exciting directions.
Mr. Crenshaw. Thank you.
For Dr. Vereshchagina, the same office working on
regenerative medicine is also responsible for gene therapy and
CRISPR technology. What should the FDA be doing to expedite the
chemistry, the manufacturing, and control of the CMC review
process, so that advances in regenerative medicine and gene
therapy vector manufacturing can move forward more quickly?
Dr. Vereshchagina. Thank you for the question.
Manufacturing issues, especially for cell and gene therapies,
are very top of mind and ripe for discussions. And this is why
industry discussed these issues with FDA. And we inserted
specific provisions in PDUFA 7 agreements that would make sure
that FDA pays attention to those issues, that there are
stakeholder discussions, that innovative manufacturing
technologies are considered for these, specifically for these
therapies, to make sure that manufacturing does not become a
roadblock, essentially, for the development and timely approval
of cell and gene therapies.
Mr. Crenshaw. Thank you, and I yield back.
Ms. Eshoo. The gentleman yields back. It is a pleasure to
recognize the gentlewoman from Delaware, Ms. Blunt Rochester,
for your 5 minutes.
Ms. Blunt Rochester. Thank you so much, Madam Chairwoman,
for the recognition, and thank you to the witnesses for being
here for this important and timely hearing on the future of
medicine.
I am pleased we are considering legislation that will
accelerate the discovery, development, delivery, and
accessibility of medical treatments and cures. I also
appreciate the opportunity to highlight issues that are
important to Delawareans and many others across the country.
Increasing diversity in clinical trials is a shared goal
among the members of this subcommittee. In late 2020 the FDA
released recommendations on approaches that sponsors of
clinical trials could take to increase enrollment in under-
represented populations in their clinical trials. The guidance
includes recommendations like broadening eligibility criteria
in later stages of development, reducing the frequency of study
visits, using mobile medical professionals, and making
participants aware of financial reimbursements for expenses
associated with participation.
Trial sponsors of almost every disease struggle with
enrolling inclusive populations, and Alzheimer's disease is no
exception. My bipartisan Equity in Neuroscience and Alzheimer's
Clinical Trials, otherwise known as the ENACT Act, builds on
these FDA recommendations, and strengthens the capacity of the
NIH to increase the participation of under-represented
populations in Alzheimer's clinical trials.
Specifically, the bill expands education and outreach to
these populations, fosters the diversity of clinical trial
staff, encourages the use of innovative trial designs, and
reduces participation burden.
Dr. Vereshchagina, do you believe that the recommendations
in the 2020 FDA guidance on enhancing the diversity of clinical
trial populations are achievable?
And what barriers are there for trial sponsors interested
in fully adopting?
Dr. Vereshchagina. Thank you for the question. So while we
don't have a position on this specific bill, we agree that new
treatments are desperately needed for Alzheimer's. And
biopharmaceutical companies are committed to research and
development in this area.
Ms. Blunt Rochester. Do you believe there are any--are
there any barriers for trial sponsors that you know of?
Dr. Vereshchagina. So, you know, in general, there are
known barriers for clinical trials. Many of them were mentioned
today, such as awareness of clinical trials; access for
patients to clinical trials who may not be able to travel to
big, established centers; lack of community-based clinical
trial sites; lack of diverse healthcare providers that can
serve as Ambassadors to make sure that there is a diverse
population participation in clinical trials.
Ms. Blunt Rochester. Great. Thank you.
And Dr. Mesa, you wrote at length about the importance of
empowering community providers to communicate openly with
trial-skeptical patients. You note that evidence suggests that
trial-skeptical patients in under-represented groups are
willing to consider participating in clinical trials if they
can discuss all of their concerns with a provider they trust.
And for that reason, my bill, the ENACT Act, would facilitate
the connection between researchers and clinicians with deep
ties to the community with cutting-edge Alzheimer's disease
research centers.
How will building bridges between study investigators and
community providers potentially increase the participation of
under-represented populations in clinical trials?
Dr. Mesa. Well, clearly, it takes teamwork to take great
care of patients, whether it be Alzheimer's or cancer. You
know, community providers, as well as other community partners,
whether it be churches, you know, other organizations and
groups, you know, and the treating physicians and the clinical
trial physicians is really critical, you know, to demystify the
process, to build trust.
To be able to understand all of the treatment options--
clinical trials are just one option, so patients really have to
understand the full scope. In south Texas we found that having
the family health expert present at the discussion of all
options, including trials, has been very impactful to try to
increase satisfaction with the process, as well as enrollment.
Ms. Blunt Rochester. Great. Thank you so much.
Last, I want to thank all of the stakeholders and the
families--many of us have been personally touched by
Alzheimer's--as well as Representatives Herrera Beutler, Smith,
Waters, and my Energy and Commerce colleague, Representative
Curtis, for working so diligently on this bill.
And I am also looking forward to passing the FDA user feed
bills on time, so that the FDA can fulfill its mission of
protecting the public health.
Thank you, Madam Chair, and I yield back.
Ms. Eshoo. I thank the gentlewoman. It is a pleasure to
recognize another one of the outstanding doctors on our
subcommittee, the gentleman from Indiana, Dr. Bucshon.
Mr. Bucshon. Well, thank you, Madam Chairwoman, and thanks
for this hearing. Thank you to all the witnesses. This will be
some ground we have already covered, as it relates to diversity
in clinical trials. But this tells you how important this is to
this subcommittee.
Many, many people on both sides of the aisle support
advancing clinical trial diversity legislation out of this
subcommittee. As a doctor, I know the importance of needing
diverse participation in trials to better understand how the
drug treatment and/or vaccine will respond to different
patients I would see in my practice, just as I know from my
medical training that certain diseases may affect certain
patients differently based on a multitude of factors, including
genetics and ethnicity.
As the future of medicine continues to move toward
personalized medicine, this will only continue to become more
and more important. That is why I partnered with my good
friend, Dr. Ruiz, to introduce H.R. 5030. This bill would help
promote clinical trials having proportionate representation of
all communities, as well as support education, outreach, and
recruitment for future clinical trials.
Currently, as we have discussed, there is a number of
external factors that make representative enrollment
challenging: for example, patient and provider awareness,
access to trial sites, and sometimes patient out-of-pocket
costs. One way to help address those barriers, which is
included in H.R. 5030, is to allow for more flexibility for
sponsors to provide additional support to individuals from
historically under-represented groups without running afoul of
the anti-kickback statute or civil monetary penalties.
Dr. Esham--is that how you pronounce your name, Esham?
Could you discuss how these interventions could or would
make trials more representative of the population?
Dr. Esham. Thank you for the question, and I will--I think
we are continuing to work with your office on this bill, and--
--
Mr. Bucshon. Yes.
Dr. Esham [continuing]. Look forward to having those
continued discussions.
We certainly, as in my written testimony stated, we
certainly see the value and the potential of decentralized
approaches, the utilization of digital health tools to help us
sort of break down some of the existing barriers that may have
led to less diverse trials in the past.
In terms of some of the other provisions, I think we just
want to work with you to make sure that--and again, I have
already said on the record----
Mr. Bucshon. Yes.
Dr. Esham [continuing]. Trial safe harbors have been very
effective. But we do want to work to make sure that any other
kinds of discussions relating to those types of things do come
with adequate protections for patients. So we just want to
continue to work with your office.
Mr. Bucshon. Understood.
Dr. Esham. I would also like to just note for the record--a
little bit of sell here, on my end--we do have some proposals
that we have developed, as well, that we think would add
additional activities, and lead to specific guidance on issues,
on additional issues that we think need to be resolved to
continue to advance a more inclusive paradigm.
Mr. Bucshon. Great. And Dr. Mesa, you touched on it in your
testimony, but could you further expand and elaborate on why
decentralized trials are so important to the promotion--and
more diverse participation in clinical trials?
And I know we have covered some of this ground, but this is
how important this is. We really need to continue this
discussion.
Dr. Mesa. So it really is critical. I think, first, you
know, aspects--as well of the bill that you have introduced--
that really helped to facilitate the community partners that
can really play a piece in that, it really is, I think, a
network, where you have really community providers potentially
playing a piece, you know, and what that looks like, the--
obviously, all the telehealth solutions, and some of that
really can even begin with, really, the initial screening for a
trial. You know, is it an option? You know, is it worthwhile
for the patient to travel to whatever center for their
enrollment?
You know, and then finally, you know, as it relates to the
critical planning piece, you know, as the trial is developed,
you know, how are these kind of telehealth solutions built in
to make the trial the most feasible for participation?
Mr. Bucshon. Yes. So you think some of the policies in 5030
could encourage a more diverse participation in clinical
trials?
Dr. Mesa. I think it could be very impactful. I think there
are several key aspects from telemedicine, the transportation,
and other that I think really could be genuinely impactful, as
I think about both the south Texas issues of diversity, but
also, really, the rural and distant barriers.
Mr. Bucshon. Yes, I just want to say in finishing that, you
know, we have seen this play out over the last couple of years
with vaccine reluctance in certain groups of our fellow
citizens, because I think a big piece--and I think a big piece
of that was the lack of diversity in the clinical trials
related to the vaccines. And, you know, people understand this,
and that is why we need to do better. This played out in real
time with vaccine reluctance in certain populations, whether it
is in rural America that I represent, or other areas of the
country.
So thank you all for being here, and I yield back, Madam
Chairwoman.
Ms. Eshoo. The gentleman yields back. It is a pleasure to
recognize the gentlewoman from New Hampshire, Ms. Kuster, for
your 5 minutes of questions.
Ms. Kuster. Thank you so much, Madam Chair, and thank you
for hosting this--chairing this important hearing.
I hear consistently from Granite Staters about how their
prescriptions are simply too expensive. I myself picked up a
prescription last month, and they charged $182. And this is a
monthly asthma medication. So I was looking at how my
constituents are having to make impossible decisions about
paying for other necessities like rent or mortgage, or food for
their children, while still taking their medications.
I think we can all agree medication is only as good as it
is affordable and accessible, and that is why I recently
introduced the Increasing Transparency in Generic Drug
Applications Act that would ensure that the Food and Drug
Administration can adequately provide feedback on proposed drug
formulations to generic drug applicants to speed up the
process, make it more streamlined, and make more generics
available to consumers. This would address a major barrier to
generic drug approval, and expedite patient access to
affordable medication.
Mr. Gaugh, could you explain why this bill is important to
patients, and how this information will expedite development
and access to complex generic drugs?
Mr. Gaugh. Thank you for the question. Yes, you are
referring to what we refer to as Q1, Q2, which is qualitative
and quantitative review.
And what we have found, since 2017--pre-2017, when we would
submit a drug, we know what the active ingredient is, we do not
know what the inactive ingredient is, or the concentration of
an active ingredient. So when we would submit a drug prior to
2017, as we went back and forth to the FDA, the FDA would
reveal what that product is, and not necessarily what the
concentration is, but would give us a range to go up and down.
Since 2017, the FDA has changed that premise. And now, when
we submit an application and we are going through that review
of trying to determine what the inactive ingredient and the
concentration is, we have to go through a controlled
correspondence process. And the FDA has limited that process to
three products in the correspondence. There are probably more
like 12 to 15 products that could be considered. We do three.
We either get accepted or rejected--many times rejected. Then
you do another one with three more. So it takes a significant
amount of time to move that forward.
Ms. Kuster. It sounds like----
Mr. Gaugh. In gaining approval.
Ms. Kuster [continuing]. A painful guessing game. In fact,
this issue was identified by the FDA in 2021 in a report
entitled, ``HHS Comprehensive Plan for Addressing High Drug
Prices as an Obstacle to Patient Access to Lower Cost Drugs.''
My bill would clarify that the FDA can provide generic drug
applicants with improved directional guidance on their proposed
formulation for complex generic drugs. This information is
critical for the development and timely approval of affordable
medicine for patients.
How important is this information for generic drug
developers, and do you think this legislation will result in
expanded patient access to affordable medication?
Mr. Gaugh. So this is critically important to our industry,
and we support your legislation that you put forward because,
as you said earlier, and I said in my previous statement, the
time that it takes to go in this back-and-forth game can be a
significant period of time, and delays access to the American
public by many, many months, if not more into years.
Ms. Kuster. Thank you.
Well, with that, Madam Chair, I hope you are pleased. I
yield back with a minute left to go.
Ms. Eshoo. Wow, you win the lottery. You win the lottery.
Very generous. We thank the gentlewoman for all of her good
work at our subcommittee.
Now it is a pleasure to recognize another member that is
respected here, another one of our doctors, Dr. Joyce from
Pennsylvania.
You have 5 minutes for your questions, sir.
Mr. Joyce. Thank you for yielding, Madam Chair Eshoo, and
thank you, Ranking Member Guthrie, for holding this hearing
today. And thank you to our distinguished panel for being
present on this rainy St Patrick's Day.
As I have said before, the safe, consistent, and prompt
approval of new pharmaceuticals, biologics, generics, and
biosimilars are critical to the health of our constituents. As
we look toward the next iteration of user fee agreements at the
FDA, it is also very important that we work to ensure continued
access of medication for all patients.
I would like to thank my colleagues, Representative Matsui,
Representative Griffith, and Representative Barragan for
working with me on legislation to fix the REMS programs that
would give the FDA authority to provide more transparency and
accountability in the REMS programs, and to end the current
disruptions that we have seen to both isotretinoin and
clozapine REMS. This will ensure better continuum of care, and
access to medications, and ensure patients and health providers
the feedback that is heard on changes to this program before
they go into effect.
I would also like to thank Congressman Levin for working
with me to introduce bipartisan Drug Manufacturing Innovation
Act, which we are considering here today. This important
legislation will codify the FDA's emerging technology program,
which will encourage better communication between the FDA and
industry to identify and resolve technical and regulatory
issues with novel technologies prior to the submission of an
application with the FDA. This approach of working with
industry will foster more innovation, and get new cures and
breakthrough therapies to the patients faster.
My first question is for you, Dr. Esham. Can you please
discuss why there is sometimes slow adoption of novel
technologies to manufacture drugs?
And the second part, do you believe regulatory uncertainty
by the FDA plays a role?
Dr. Esham. So I--hopefully, I am answering your question,
but I just wanted to point out that we are supportive of your
bill. We strongly support the emerging technology programs
mission, and want to continue to--I believe it will have great,
great benefit, including with the guidance and the funding.
And I may need you to repeat the question one more time.
Mr. Joyce. Do you think that, by having regulatory
uncertainty in the FDA, that that plays a significant role in
allowing manufacturers to get these great new novel medicines
that patients need?
Dr. Esham. I think we are always working with the FDA to
try to get regulatory clarity across the board. And again, the
more novel a medicine is, where the less precedent is, the more
you have to really engage with the FDA on a very active basis.
And we at BIO really try to work with our members to do that on
a very timely basis to avoid undue delays.
Mr. Joyce. And do you think that access to innovation
really should be one of the components of American access to
medicine, American ingenuity, and American healthcare?
Dr. Esham. Yes. I mean, I--you know, I think we should
all--you know, when we reflect upon what we have done in terms
of transforming medicines to date, it is really just--we should
always be thinking about that as the first step, and really try
to keep working toward the next vision of really transforming
how we can provide better care for patients.
Mr. Joyce. I think you nailed it with that comment, that
that is an obligation both here, as Members of Congress, and as
industry to provide better medication for our patients.
Finally, I want--do want to flag some concerns that I have
with proposed changes to the accelerated approval pathway. Dr.
Vereshchagina, would it be accurate to say that since only
medicines for serious conditions that address an unmet medical
need are eligible for this pathway, that the accelerated
approval offers significant benefits to patients by making
important medicines available much earlier than would have
otherwise been the case?
Dr. Vereshchagina. Absolutely, and thank you for this
question. I think it is always important to remember the
original intent of this bill, that--exactly what you said, it
is to provide access to medicines for patients with serious and
life-threatening conditions who otherwise don't have options.
And it is critical that the--what the accelerated approval
pathway does, in its current form, to providing that ability
for industry to continue to invest in research and development
for those unmet medical needs, and have that regulatory
predictability to deliver safe and effective medicines for
patients who otherwise would not have those medicines.
Mr. Joyce. Thank you. I see my time has expired.
Thank you, Madam Chair, again for convening this important
hearing today. I yield.
Ms. Eshoo. Thank you. The gentleman yields back.
The Chair now recognizes the gentlewoman from Washington
State, another outstanding doctor on our subcommittee, Dr.
Schrier.
You have 5 minutes for your questions.
Ms. Schrier. Well, thank you, Madam Chair, and thank you to
the witnesses for coming today and sharing your knowledge. And
thank you to all of my colleagues for putting forward these
important pieces of legislation.
I am particularly happy to see Representatives DeGette and
Upton's bill, Cures 2.0, on the docket for today. Dr. Bucshon
and I have a provision in this bill, the Meaningful Access to
Federal Health Plan Claims Data Act--there is a mouthful--which
allows clinical researchers to have access to Medicare claim
data.
So this means that physician researchers can see trends in
patient diagnoses and treatments, giving them data that can
help both with research and with providing better care for
their patients. And it is well known, for example, that some
medications work better for some patients. And often we figure
this out by trial and error, but later find out that there is
actually certain sub-categories of patients that make them more
or less likely to respond to a given medication. And without
big data from CMS, from Medicare, it can take a long time to
figure that out. So access to those vast quantities of data can
help define which patients will do best with which medications,
for example. And that is good for patients, for timing and for
pocketbooks.
Now, there is another example, which I thought was
interesting. Like, some cardiothoracic surgery patients do
worse after a blood transfusion. And with only a handful of
cases, a surgeon might just assume that these were random, bad
luck. But having access to massive troves of Medicare data
allowed clinical researchers in Virginia to find patterns, and
discern which specific characteristics and medical histories of
those patients made them more likely to worsen. And that means
doctors can give better care and be highly vigilant for adverse
outcomes if those patients need blood transfusions.
Dr. Ramachandran, in your testimony you point out the
important transparency in post-market approvals, clinical
trials, and more. And as a practicing physician, can you just
briefly talk about how having access to Medicare claims data
and more data just helps you do research to treat your patients
at Yale?
Dr. Ramachandran. Yes, definitely. Thank you, Congressman,
for the question.
The--you know, that provision is so important, especially
as a physician researcher, but someone who takes care of
patients. You know, we have talked today about the limitations
of clinical trials in terms of sometimes not enrolling patients
from certain populations who have certain disease conditions,
and so that makes it so critically important to have robust
post-marketing surveillance and, really, access to data such as
claims data, so that we actually know whether or not the drug
actually works in the patient that we are seeing in the
hospital or the exam room.
And so for me, as a practicing physician, I really want to
know whatever drug or device I am going to be prescribing or
recommending to a patient actually works with them, works for
them. And that sort of claims data is just so critical, not
just to inform my own practice, but also the guidelines of
rapidly, you know, changing medical practice, so that we can be
able to do better medicine for our patients.
Ms. Schrier. Thank you. It is almost like a macro level of
precision medicine.
I wanted to turn my attention--because transparency is a
theme today, I want to pivot to drug--to medications. Mr.
Gaugh, I was flabbergasted when I read your testimony detailing
the process that generic drug manufacturers have to go through
to get to the market.
I think we all know that they have to match up exactly in
quantity and quality with the active ingredient. But you talked
about having to exactly match the inactive ingredients, the
fillers, the things that really don't impact efficacy, and that
they can't just get that information from the brand name
manufacturer, they have to go in and guess, and sort of trial-
and-error this, which can really delay the arrival of these
generics to market. That is incredibly frustrating, as a
patient, but also as a legislator and a doctor, to know that
this kind of guessing game is keeping less expensive
medications from our patients.
Can you point out some of the commitments in GDUFA 3 and
the BsUFA 3 that will help increase transparency and,
ultimately, facilitate this speeding of generics to market--and
biosimilars?
Mr. Gaugh. Thank you for the question. We did have these
discussions during GDUFA 3. But unfortunately, no resolution
came out of that. So I am very happy to see this bill come
forward around Q1, Q2, and being able to get the information.
In an earlier statement I noted that the FDA, prior to
2017, did provide that information without what we call a back-
and-forth guessing game of what that product is. So we would
submit a--now, today--we submit a controlled correspondence
with just three products in it, three inactive ingredients. The
FDA would then come back and say either, yes, that is
acceptable, or no, it is not. If it is not, then we go back
with three more ingredients, and three more, until we do get an
acceptable.
So this changed in 2017, as I said a few minutes ago, and
so we are looking forward to a bill like this that would move
that back to giving that information. Because, prior to 2017,
they would tell us what that inactive ingredient was.
Concentration, we still had to kind of go with thumbs up,
thumbs down, whether we were headed in the right direction. But
it was a much, much quicker and much less guessing game. Thank
you.
Ms. Schrier. Thank you. My team will stay in touch with you
about that provision, and I yield back.
Mr. Gaugh. Wonderful.
Ms. Eshoo. The gentlewoman yields back. Let's see, the
gentlewoman from--you are good on your side? OK. Hold on,
witnesses. This is going to end.
Mr. Guthrie. No, we don't have anybody.
Ms. Eshoo. This is going to end pretty soon. For your
patience, we all thank you.
The gentlewoman from Massachusetts, Mrs. Trahan, you have--
recognized for 5 minutes.
Mrs. Trahan. Well, thank you, Chairwoman Eshoo. Thank you,
Ranking Member Guthrie, for convening this hearing. Thank you
to the witnesses for your patience and your expertise.
Over the past 2 years we have seen how streamlined
development and approval processes, specifically for COVID-19
vaccines and therapeutics, have been critical to saving lives.
And I am thrilled that this committee is considering the 22
bills before us today to broaden that focus to encompass
additional diseases that currently lack robust biomedical
research and innovative treatments.
Patients from under-representative populations are
disparately impacted throughout our medical system, from cancer
treatments to drug development to sepsis detection algorithms.
And the need for diversity in clinical trials, which we have
been discussing today, mirrors a similar need for diversity in
data sets used to train medical software, an issue my office
has been working on.
So, Dr. Mesa, my first question is for you. When a clinical
trial's results are not statistically significant for a given
sub-population, how are those limitations communicated to
physicians?
Dr. Mesa. So certainly several mechanisms, both in terms
of, you know, as a result, is published in a manuscript.
But really, the greater discussion that occurs, you know,
at national meetings, you know, and subsequent activities--you
know, it is critical--there are times we just don't have the
power to detect a difference, but we suspect that a difference
may be there, and requires additional trials to be performed,
additional sub-analysis to be performed, or for us to be able
to try to tap into, you know, other experiences after a drug is
developed, in terms of real-world evidence.
So it is a challenge. I think that is a challenge we all
feel in terms of--you know, sometimes we just don't have enough
power in a study to be able to answer all the questions that
are relevant.
Mrs. Trahan. Sure. And as a medical practitioner, what do
you think about as you work with patients from groups
traditionally under-represented in clinical trials?
I mean, do you yourself take extra steps when you notice
unusual reactions to drugs or treatments?
Dr. Mesa. Most definitely. You know, it is really a
critical piece.
Colleagues in Ecuador identified an unusual reaction to a
medicine we frequently use here, in the United States,
rituximab. That was related to, you know, indigenous cuisine
of--the medicine is developed out of Chinese hamster ovary
cells. And these individuals that have had guinea pigs as part
of their diet, you know, had unusual reactions.
So again, just a bit of an extreme example, but again,
different cultural pieces, whether it be related to genetics,
culture, or diet, sometimes might have some really unexpected
consequences. And then we try to communicate these to really be
sensitive to those differences.
Mrs. Trahan. Got it. Thank you for that.
Dr. Esham, when crafting and designing a trial, do trial
sponsors take steps to determine whether a trial is
significantly diverse? And if so, how do they do that?
Dr. Esham. I mean, they often do do that. I think what we
have heard from our member companies, and where we want to
drive activities that can lead to regulatory alignment about
approaches for all clinical development programs--and that is
we need to address some gaps in our data--in our reliable data
sources.
We need to come up with some methodologies and a line of
methodologies about how we can use the data that is available,
why we are continuing to improve the data that will help us
establish targets that are representative of the patient
population. So we have heard that as a sort of inconsistent
barrier that we want to resolve.
So that is just one example of some of the proposals that
we have brought forward to this committee.
Mrs. Trahan. Thank you for that. Well, I certainly look
forward to passing legislation aimed at ensuring thorough
testing and research, that medical treatments are safe and
effective for all members of our society, and I appreciate the
time.
I appreciate this hearing, again, and these 22 bills being
brought forward, Madam Chair. With that, I will yield back.
Ms. Eshoo. The gentlelady yields back. The gentleman from
California, Mr. Cardenas, good to see you, and you have 5
minutes.
Mr. Cardenas. Thank you so much, Madam Chairwoman, and also
thank you to Ranking Member Guthrie.
This hearing is incredibly enlightening, and I want to
thank all the incredible witnesses for all of your professional
testimony and giving us some information about what is going on
today, and what we need to do better in our country.
I apologize, I had to step away from the committee just for
a little bit, as 988, when it comes to mental health, is going
to be live in July of this year, which is a great thing, and we
need to make sure that we do our part in Congress to support
it.
I want to spend time today talking about the importance of
vetting therapies and clinical trials that mirror demographics
nationwide. There is no question that this is desperately
needed to ensure the safety and efficacy of drugs for everyone,
especially in an increasingly diversifying country with
pronounced health inequities from community to community.
Clinical trial diversity is something we hear is a priority
across the board, thank God, but not just on principle, but as
something that benefits every actor in the process: from
industry, who wants to produce a high quality, effective
product, from the agencies that want to protect patients, and
from consumers who want assurances that their medications will
work for them just as intended. Despite the consensus, we hear
concerns about hesitancy and inability to recruit patients of
color to participate in clinical trials.
Dr. Mesa, you have clearly had some success in recruitment
efforts at the Mays Cancer Center. I am thrilled to hear that
you were able to boost enrollment of Hispanics from 46 percent
to 56 percent after instituting demographic-specific plans. Can
you give us an example of how you were able to do that, and
maybe something that could be enlisted as a best practice in
other trials?
Dr. Mesa. So it is a mandatory part of our protocol review
process now that the investigators and the entire team really
reflect on each trial individually. All of these trials are
quite heterogeneous. And as we reflect on the eligibility
criteria, as we reflect on the conduct of the study, the
ability to have transportation support or others--we have
provided transportation support through philanthropic funding,
you know, as one mechanism to help to support individuals.
What we found is every trial is different, and really
trying to have a plan per trial is really critical.
I think the other piece of this, without question, is
increased feedback that we are having with our colleagues in
the pharmaceutical industry, really, regarding the actual
design of the study, the eligibility criteria, but also the
rigorousness of the number of visits, the utilization of
telehealth all can have a real impact on best practices.
Mr. Cardenas. Well, thank you. And with that, your response
highlights the need for clear and enforceable benchmarks as
such. I am proud to be a co-lead on a bill which has to do with
Clinical Trial Diversity Act of 2021, which would help
institute these types of requirements for NIH-funded trials.
I believe the Clinical Trial Diversity Act is a necessary
step to ensuring that our therapies work for everyone. And I am
grateful for my colleague, Representative Robin Kelly, who has
been a true leader on this legislation and other pieces of
legislation like it.
Finally, just to pivot briefly, I would also like to State
that I am pleased to see that legislation to move away from
animal testing is being considered, especially as more human-
centered alternatives continue to emerge and become more of a
standard. I am supportive of many bills that attempt to make
this transition, and I believe we need to consider a host of
measures to achieve this goal. Focusing on more humane
approaches when possible is beneficial for both animals and
humans.
Dr. Mesa, I would also like to ask you if you have had
success on recruiting not only at the college level, or earlier
in people's decisions to get into healthcare.
Dr. Mesa. I hope that we have made a difference by trying
to really engage people earlier and earlier in their career----
Mr. Cardenas. Have you been able to engage people at
younger ages? Middle school, high school?
Dr. Mesa. So we have gone down to the high school level,
but certainly it is under consideration, you know. How do we
make careers in healthcare and STEM, you know, attractive for,
you know, the people in our community? We live in a minority-
majority community in San Antonio, in south Texas. And it is a
key part. You know, giving opportunities, internships,
opportunities to really grow and succeed along a variety of
paths.
Mr. Cardenas. Thank you. I have been to south Texas, a lot
of hard-working, beautiful families, mostly Latino families.
And I would love to see them use their talents and abilities in
this field.
With that, my time has expired. I yield back. Thank you so
much, Madam Chairwoman.
Ms. Eshoo. The gentleman yields back, and now the ever-
patient, ever-present Congresswoman Diana DeGette, who is the
lead author, together with Mr. Upton, on Cures 2.0.
So thank you, Diana----
Ms. DeGette. Thank you so much.
Ms. Eshoo [continuing]. You are recognized for 5 minutes.
Ms. DeGette. Madam Chair, thank you so much. Thank you for
your leadership. For somebody who is kind of a medical research
wonk, I don't like anything more than sitting here listening to
these 22 bills being discussed. And I want to thank you for
your partnership with me and Chairman--or Congressman Upton on
both ARPA-H and Cures 2.0. These bills will move together, and
they will be revolutionary.
So, you know, when Fred and I teamed up in 2015, we really
did envision a transformative bill that would accelerate the
discovery, development, and delivery of medical treatments and
cures. And when I hear about all these bills today, and I think
about the things we did in that bill that started the movement,
I am so thrilled to see these bills moving it ahead.
For example, my friend, Congressman Cardenas, was talking
about the Clinical Trial Diversity Act, which is such an
important key. And in 21st Century Cures we started that
movement toward diversity in clinical trials, and many, many
other issues.
And so I want to ask you, Dr. Esham, how have the policies
that were included in 21st Century Cures, like NIH's
regenerative medicine innovation project, FDA's real-world
evidence program, and patient-focused drug development impacted
the progression of biomedical innovation?
Dr. Esham. The simple answer is very positively. And it
really has led to--I think it built a lot of foundations for
continued innovation in how we approach drug development, how
we enable the development of novel treatments. So again, it has
been very important and very beneficial.
Ms. DeGette. And do you think there is more that we can do
to improve existing research and regulatory pathways to help
the progress of medical innovation?
Dr. Esham. Well, I have been working with biotechnology
companies for the better part of 12 years, and I think we are
always of the mindset we can always do better, we all--we must
always improve. And there is always a new vision to be met. So
there is always more work to be done.
Ms. DeGette. And have you looked at Cures 2.0?
Dr. Esham. Yes, and I can----
Ms. DeGette. And what is your organization's view of that
bill?
Dr. Esham. Yes, and I can quickly--I will try to be
succinct.
We are very supportive of the provision relating to the
advancement of digital technologies and real-world evidence.
We are supportive of the provisions relating to increasing
clinical trial diversity.
And again, we have some additional ideas we would love to
talk with you about.
And we were very supportive of the provision that
reinforces the importance of PASTEUR. And as I stated earlier
in my testimony, you know, we must recognize that antimicrobial
resistance is a leading cause of death, and it does have unique
challenges to getting incentive and driving development of
those medicines. So we really urge Congress to pass PASTEUR
this year.
Ms. DeGette. Thank you. Dr. Allen, how have previous Cures
policies benefited patients and their loved ones?
Dr. Allen. Well, thank you very much for your leadership on
both initiatives. I think what was very quickly seen from the
Cures 1.0 initiative, what really stands out, were the
provisions to operationalize aspects related to patient
experience and patient-focused drug development.
And I think before Cures 1, there was at least initial
attempts to think about ways to engage patients more
frequently. But through the operational steps around
methodology and processes that were laid out in the first Cures
provisions, it really enabled those to move forward. And we
have seen that, in terms of an understanding and more available
information for patients.
Ms. DeGette. And have you looked at Cures 2.0, Dr. Allen?
Dr. Allen. We have.
Ms. DeGette. And do you think that Cures 2.0 helps further
that even more?
Dr. Allen. Absolutely. I think there is important
provisions in 2.0 that recognized the advancement of technology
specific around things related to cell and gene therapies,
including aspects around looking at additional systematic
enhancements such as the improved communication between CMS and
FDA to ensure that there is a timely handoff between these new
breakthroughs that are being enabled through a strong research
system to make it all the way accessible for patients.
Ms. DeGette. Great. Thank you. And have you looked at Cures
2.0? Does Friends of Cancer Research support that legislation?
Dr. Allen. We absolutely support it, and I look forward to
working with you as you move forward through the process.
Ms. DeGette. Great, thanks.
Thank you so much, Madam Chair. I yield back.
Ms. Eshoo. The gentlewoman yields back. And it is a
pleasure to recognize the gentleman from New York, who is--are
you waiving on? Yes.
Just so that the witnesses know, members of the full
committee who are not members of our subcommittee choose to
waive on, and we always welcome from both sides of the aisle
when they do so.
Congresswoman DeGette has waived on today, and now, Mr.
Tonko, you are waiving on, and you have 5 minutes.
Mr. Tonko. Thank you, Madam Chair, for allowing me to waive
on and, more importantly, for your leadership of the
Subcommittee on Health.
And again, thanks to Chair Eshoo, and Ranking Member
Guthrie, and Chair Pallone, and Ranking Member McMorris Rodgers
for including the Helping Experts Accelerate Rare Treatments
Act of 2022, or the HEART Act, on today's agenda.
I wanted to take a moment and thank Chair Pallone and his
staff for their energy and dedication to working with my office
to develop this HEART Act fully.
Three years ago I had the pleasure of meeting a
constituent, Melissa Goetz, who is the co-president of the
Familial Chylomicronemia Syndrome, or FCS, Foundation. FCS is a
rare genetic condition that causes a buildup of fats in the
blood that can increase the risk of severe abdominal pain and
potentially fatal attacks of pancreatitis. FCS presents a
significant risk of severe and life-threatening attacks of
pancreatitis and early death, even amongst patients who are in
treatment to manage the condition. Melissa's daughter,
Giuliana, was diagnosed with FCS when she was three weeks old.
She was hospitalized with pancreatitis, a liver infection, and
kidney infection at seven weeks old. Well, I am pleased to
share that Giuliana is doing well today.
It came to my attention that potential treatment for this
condition was ultimately rejected, in part because it would
require a weekly blood draw that the Food and Drug
Administration deemed to--as too burdensome to patients. This
prompted me to consider how FDA is currently engaging with
patients, especially those that suffer from rare and ultra-rare
diseases that do not have treatment options today.
I drafted the HEART Act with my friend and colleague,
Congressman McKinley, to ensure that FDA is appropriately
engaging with medical experts and patients during its review
process.
The HEART bill requires an annual report to Congress to
better understand how FDA processes submissions for treatments
for rare diseases, and how it engages with external experts
such as patients and physicians.
It also requires a study to do better--to better understand
how the EU manages its rare disease treatment reviews.
It has the Government Accountability Office assess how the
FDA is engaging patients and experts in the review process, and
provide recommendations to improve these interactions in the
future.
It also requires the FDA to hold a public meeting to
solicit feedback from patients, patient groups, and medical
experts on how it could better incorporate its expertise during
a review of a treatment.
Dr. Allen, the HEART Act is designed to better incorporate
both the patient and rare disease or small population studies
medical experts' perspective during the FDA review process. Do
you agree that, especially as it relates to rare and ultra-rare
conditions, that we can do more to better incorporate the
patient and rare disease medical experts in that FDA process?
Dr. Allen. Definitely. I think we have seen that across
other therapeutic areas, where enhanced communication very
early on with FDA has been beneficial in designing the studies
appropriately to get new medicines forward, but also helping
them in their regulatory review, ultimately.
Mr. Tonko. Thank you.
And Dr. Mesa and Dr. Esham, can we do more to better
incorporate the patient and rare disease expert perspective
into the FDA process?
Dr. Esham. I concur with my colleague, Jeff. I mean, there
is always benefit to ensuring more engagement with more
experts, particularly in diseases that--where little precedent
is set, or just newly diagnosed.
And I would also like to say I am glad to hear, in the
story that you told, that the individual is doing better.
Mr. Tonko. Yes. Thank you, Doctor.
And Dr. Mesa?
Dr. Mesa. Yes, most certainly. I did participate--I focus
on rare chronic leukemias, and was involved with kind of an FDA
listening session--again, really led by patients, where they
brought in patient voices, really, from across the spectrum of
disease to both counsel on clinical trials, that process, as
well as, you know, what were clinically meaningful endpoints.
So I think that is an important piece for rare diseases.
Mr. Tonko. Thank you. And I also would like to note my
strong support for the Prevent Interruptions in Physical
Therapy Act, which is about locum tenens, the ability to bring
in a replacement provider during a provider's temporary
absences for illness, pregnancy, vacation, or continuing
medical education. The 21st Century Cures Act contained a
provision that added physical therapists to the healthcare
professionals that may use locum tenens under Medicare, but was
limited for rural and under-served regions. The Prevent
Interruptions in Physical Therapy Act would expand this for all
geographic regions.
So I look forward to working with the sponsors of Cures 2.0
to get this included as the legislation moves through the
process, as we did back when it was included in Cures 1.0. This
will indeed benefit both physical therapists and their patients
who rely on these vital services.
And with that, Madam Chair, I yield back. And again, thank
you.
Ms. Eshoo. The gentleman yields back.
We don't have any other members that are requesting time,
correct, on both sides?
OK. I have a unanimous consent request to enter 46
documents into the record.
Mr. Guthrie. No objection----
Ms. Eshoo. Thank you very much.
Mr. Guthrie. Unless they want you to read all those----
[Laughter.]
Ms. Eshoo. No, that is all right. As long as you don't, I
won't.
[The information appears at the conclusion of the hearing.]
Ms. Eshoo. On a serious note, in looking at this, this is
really an honor roll of both individuals and organizations in
our country that are weighing in.
I want to thank each one of you, the witnesses. This has
been a very long legislative hearing, but 22 bills, 22 bills.
And I am proud of all of the members, their work from both
sides of the aisle, and each one of you, because you have
added, you know, the texture, the richness, the different
layers of the legislation, most, most helpful.
So you have been here for, let's see, three-and-a-half--I
would say three-and-a-half hours. You have more than earned
your keep with us. So thank you to each one of you, to the
staffs on both sides of the aisle of the committee.
And members do have ten business days to submit additional
questions for the record. So witnesses, we ask that you respond
to promptly to any questions that are submitted to you that you
receive.
So with that, with our lasting gratitude to all of you, the
subcommittee is adjourned.
[Whereupon, at 2:07 p.m., the subcommittee was adjourned.]
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