[House Hearing, 113 Congress]
[From the U.S. Government Publishing Office]
21ST CENTURY CURES: EXAMINING WAYS TO COMBAT ANTIBIOTIC RESISTANCE AND
FOSTER NEW DRUG DEVELOPMENT
=======================================================================
HEARING
BEFORE THE
SUBCOMMITTEE ON HEALTH
OF THE
COMMITTEE ON ENERGY AND COMMERCE
HOUSE OF REPRESENTATIVES
ONE HUNDRED THIRTEENTH CONGRESS
SECOND SESSION
__________
SEPTEMBER 19, 2014
__________
Serial No. 113-178
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Printed for the use of the Committee on Energy and Commerce
energycommerce.house.gov
______
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COMMITTEE ON ENERGY AND COMMERCE
FRED UPTON, Michigan
Chairman
RALPH M. HALL, Texas HENRY A. WAXMAN, California
JOE BARTON, Texas Ranking Member
Chairman Emeritus JOHN D. DINGELL, Michigan
ED WHITFIELD, Kentucky Chairman Emeritus
JOHN SHIMKUS, Illinois FRANK PALLONE, Jr., New Jersey
JOSEPH R. PITTS, Pennsylvania BOBBY L. RUSH, Illinois
GREG WALDEN, Oregon ANNA G. ESHOO, California
LEE TERRY, Nebraska ELIOT L. ENGEL, New York
MIKE ROGERS, Michigan GENE GREEN, Texas
TIM MURPHY, Pennsylvania DIANA DeGETTE, Colorado
MICHAEL C. BURGESS, Texas LOIS CAPPS, California
MARSHA BLACKBURN, Tennessee MICHAEL F. DOYLE, Pennsylvania
Vice Chairman JANICE D. SCHAKOWSKY, Illinois
PHIL GINGREY, Georgia JIM MATHESON, Utah
STEVE SCALISE, Louisiana G.K. BUTTERFIELD, North Carolina
ROBERT E. LATTA, Ohio JOHN BARROW, Georgia
CATHY McMORRIS RODGERS, Washington DORIS O. MATSUI, California
GREGG HARPER, Mississippi DONNA M. CHRISTENSEN, Virgin
LEONARD LANCE, New Jersey Islands
BILL CASSIDY, Louisiana KATHY CASTOR, Florida
BRETT GUTHRIE, Kentucky JOHN P. SARBANES, Maryland
PETE OLSON, Texas JERRY McNERNEY, California
DAVID B. McKINLEY, West Virginia BRUCE L. BRALEY, Iowa
CORY GARDNER, Colorado PETER WELCH, Vermont
MIKE POMPEO, Kansas BEN RAY LUJAN, New Mexico
ADAM KINZINGER, Illinois PAUL TONKO, New York
H. MORGAN GRIFFITH, Virginia JOHN A. YARMUTH, Kentucky7
GUS M. BILIRAKIS, Florida
BILL JOHNSON, Missouri
BILLY LONG, Missouri
RENEE L. ELLMERS, North Carolina
Subcommittee on Health
JOSEPH R. PITTS, Pennsylvania
Chairman
MICHAEL C. BURGESS, Texas FRANK PALLONE, Jr., New Jersey
Vice Chairman Ranking Member
ED WHITFIELD, Kentucky JOHN D. DINGELL, Michigan
JOHN SHIMKUS, Illinois ELIOT L. ENGEL, New York
MIKE ROGERS, Michigan LOIS CAPPS, California
TIM MURPHY, Pennsylvania JANICE D. SCHAKOWSKY, Illinois
MARSHA BLACKBURN, Tennessee JIM MATHESON, Utah
PHIL GINGREY, Georgia GENE GREEN, Texas
CATHY McMORRIS RODGERS, Washington G.K. BUTTERFIELD, North Carolina
LEONARD LANCE, New Jersey JOHN BARROW, Georgia
BILL CASSIDY, Louisiana DONNA M. CHRISTENSEN, Virgin
BRETT GUTHRIE, Kentucky Islands
H. MORGAN GRIFFITH, Virginia KATHY CASTOR, Florida
GUS M. BILIRAKIS, Florida JOHN P. SARBANES, Maryland
RENEE L. ELLMERS, North Carolina HENRY A. WAXMAN, California (ex
JOE BARTON, Texas officio)
FRED UPTON, Michigan (ex officio)
C O N T E N T S
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Page
Hon. Joseph R. Pitts, a Representative in Congress from the
Commonwealth of Pennsylvania, opening statement................ 1
Prepared statement........................................... 2
Hon. Frank Pallone, Jr., a Representative in Congress from the
State of New Jersey, opening statement......................... 3
Hon. Phil Gingrey, a Representative in Congress from the State of
Georgia, opening statement..................................... 5
Hon. Henry A. Waxman, a Representative in Congress from the State
of California, opening statement............................... 7
Hon. Louise M. Slaughter, a Representative in Congress from the
State of New York, prepared statement.......................... 9
Hon. Fred Upton, a Representative in Congress from the State of
Michigan, prepared statement................................... 146
Witnesses
Janet Woodcock, Director, Center for Drug Evaluation and
Research, U.S. Food and Drug Administration.................... 10
Prepared statement........................................... 12
Answers to submitted questions............................... 162
Kenneth J. Hillan, Chief Executive Officer, Achaogen, Inc........ 43
Prepared statement........................................... 47
Answers to submitted questions............................... 179
Barbara Murray, President, Infectious Disease Society of America. 55
Prepared statement........................................... 57
Answers to submitted questions............................... 184
Adrian Thomas, Vice President, Global Market Access and Global
Public Health, Janssen Global Services, LLC.................... 76
Prepared statement........................................... 79
Answers to submitted questions............................... 193
Kevin Outterson, Professor of Law, Boston University School of
Law............................................................ 92
Prepared statement........................................... 94
Answers to submitted questions............................... 202
Allan Coukell, Senior Director, Drugs and Medical Devices, The
Pew Charitable Trusts.......................................... 112
Prepared statement........................................... 114
Answers to submitted questions............................... 209
Dr. John H. Powers, Assistant Clinical Professor of Medicine,
George Washington University School of Medicine................ 125
Prepared statement........................................... 127
Answers to submitted questions \1\........................... 213
Submitted Material
Article entitled, ``Andrew J. Moyer and Penicillin: Saving Lives
on a Grand Scale,'' in Moment of Indiana History, August 23,
2010, submitted by Mr. Burgess................................. 147
Statement of the Flag & General Officers' Network, Inc.,
submitted by Stephen Parente................................... 149
Statement of Cubist Pharmaceuticals, submitted by Mr. Pitts...... 151
Statement of California Healthcare Institute, submitted by Mr.
Pitts.......................................................... 159
----------
\1\ Dr. Powers did not respond to questions for the record.
21ST CENTURY CURES: EXAMINING WAYS TO COMBAT ANTIBIOTIC RESISTANCE AND
FOSTER NEW DRUG DEVELOPMENT
----------
FRIDAY, SEPTEMBER 19, 2014
House of Representatives,
Subcommittee on Health,
Committee on Energy and Commerce,
Washington, DC.
The subcommittee met, pursuant to call, at 9:00 a.m., in
room 2123, Rayburn House Office Building, Hon. Joseph R. Pitts
(chairman of the subcommittee) presiding.
Present: Representatives Pitts, Burgess, Shimkus, Gingrey,
Lance, Bilirakis, Ellmers, Pallone, Green, and Waxman (ex
officio).
Also Present: Representative DeGette.
Staff Present: Clay Alspach, Counsel, Health; Gary Andres,
Staff Director; Sean Bonyun, Communications Director; Leighton
Brown, Press Assistant; Noelle Clemente, Press Secretary; Paul
Edattel, Professional Staff Member, Health; Sydne Harwick,
Legislative Clerk; Robert Horne, Professional Staff Member,
Health; Carly McWilliams, Professional Staff Member, Health;
Tim Pataki, Professional Staff Member; Chris Sarley, Policy
Coordinator, Environment and Economy; Heidi Stirrup, Health
Policy Coordinator; Ziky Ababiya, Minority Staff Assistant;
Eric Flamm, Minority FDA Detailee; Karen Nelson, Minority
Deputy Committee Staff Director For Health; Rachel Sher,
Minority Senior Counsel.
OPENING STATEMENT OF HON. JOSEPH R. PITTS, A REPRESENTATIVE IN
CONGRESS FROM THE COMMONWEALTH OF PENNSYLVANIA
Mr. Pitts. The subcommittee will come to order. The chair
will recognize himself for an opening statement.
According to the World Health Organization's Antimicrobial
Resistance, Global Report on Surveillance 2014, antimicrobial
resistance, AMR, is an increasingly serious threat to global
public health. British Prime Minister David Cameron warned in
July that if we do not confront the threat of antibiotic
resistance, we could be ``cast back into the dark ages of
medicine where treatable infections and injuries will kill once
again.''
And just yesterday, the President announced an executive
order focused on efforts his administration plans to take with
regards to the antibiotic resistance issue. In 2012, this
committee sought to help combat this global threat by passing
the GAIN Act as part of the Food and Drug Administration Safety
and Innovation Act of 2012. The GAIN Act was an important first
step in the fight against antibiotic resistance and a great
example of how bipartisan collaboration on this committee can
save lives. And I want to commend the bipartisan authors that
made GAIN possible, including Representatives Gingrey, Green,
Shimkus, DeGette, Whitfield, and Eshoo for their leadership.
I also want to commend the FDA for its role in making GAIN
a success since its passage. But what is clear to many in this
room is that GAIN did not fully fix the problem, and much more
is needed if we are to incentivize the type of drug development
needed to combat this global threat.
And to that end, Congressmen Gingrey and Green have
introduced another piece of legislation, the ADAPT Act, which
would seek to address problems related to the FDA approval
process of antibiotic drugs. It is one of a series of proposals
that warrants serious consideration by this committee as part
of our 21st Century Cures, and I want to thank them for their
continued efforts in this space.
I would like to thank all of our witnesses for being here
today and yield the remainder of my time to the vice chair of
the subcommittee, Dr. Burgess.
[The prepared statement of Mr. Pitts follows:]
Prepared statement of Hon. Joseph R. Pitts
The Subcommittee will come to order.
The Chair will recognize himself for an opening statement.
According to the World Health Organization's (WHO)
Antimicrobial Resistance: Global Report on Surveillance 2014,
``Antimicrobial resistance (AMR) is an increasingly serious
threat to global public health.''
British Prime Minister David Cameron warned in July that if
we do not confront the threat of antibiotic resistance, we
could be ``cast back into the dark ages of medicine where
treatable infections and injuries will kill once again.''
And, just yesterday, the President announced an Executive
Order focused on efforts his administration plans to take with
regards to the antibiotic resistance issue.
In 2012, this Committee sought to help combat this global
threat by passing the GAIN Act as part of the Food and Drug
Administration Safety and Innovation Act of 2012.
The GAIN Act was an important first step in the fight
against antibiotic resistance and a great example of how
bipartisan collaboration on this committee can save lives.
I want to commend the bipartisan authors that made GAIN
possible including Reps. Gingrey, Green, Shimkus, DeGette,
Whitfield and Eshoo for their leadership.
I also want to commend the FDA for its role in making GAIN
a success since its passage.
But what is clear to many in this room is that GAIN didn't
fully fix the problem and much more is needed if we are to
incentivize the type of drug development needed to combat this
global threat.
To that end, Congressmen Gingrey and Green have introduced
another piece of legislation, the ADAPT Act, which would seek
to address problems related to the FDA approval process of
antibiotic drugs.
It is one of a series of proposals that warrants serious
consideration by this Committee as part of our 21st Century
Cures and I want to thank them for their continued efforts in
this space.
I would like to thank all of our witnesses for being here
today, and I yield the remainder of my time to Rep. ----------
------------------.
Mr. Burgess. Thank you, Mr. Chairman, and I certainly
appreciate the fact we are having this hearing today. It is
necessary as we proceed with the Cures initiative to talk about
some of the things that are most important, some of the things
that are relied upon and familiar in our front line of our
ability to fight infections and those are antibiotics.
Antibiotic resistance, specifically resistant strains, is a
growing problem. Equally troubling, despite widespread support,
is the lack of a pipeline of new drugs that can improve on
previous generations or fight drug resistance strains. A lot of
facets to this issue, and there is no single silver bullet
solution.
But here is the deal, our drug arsenal is our drug arsenal.
Today the committee continues to probe the various market
reasons why we are not producing new antibiotics, and if the
proper market incentives and regulatory pathways exist to
encourage the development of new drugs. Very important strides
that have been made in the FDA Safety and Innovation Act, most
notably through the GAIN Act, but they were just the first
steps. Part of the deal is once nature adapts, it is hard to
force nature to unadapt. These resistant strains are out there,
and they aren't going away. Once this evolutionary leap has
taken place, we are not going back, and that is why we need a
continuous pipeline of new drugs.
I would also just point out on a historical note, since the
election in Scotland was yesterday, and Scotland is going to
remain part of the British empire, and of course, it was a
famous Scotsman, Sir Alexander Fleming who developed, or is
credited with the discovery of penicillin, but Sir Alexander
Fleming couldn't produce a lot of penicillin, and it was Andrew
Moyer from Indiana, who actually developed the deep
fermentation process that allowed the penicillin to be mass
produced and really made a significant difference in the lives
of our soldiers returning--or the saving of lives of our
soldiers returning from World War II, and parenthetically
dropped the cost of a course of penicillin from $20, at that
time was a significant amount of money, to less than 50 cents.
So we know we can do this and we know we should do this,
that is, we have done it before, so the forefront of
innovation, and that is what the Cures Initiative is all about,
and I think that is an important part of our discussion. I will
submit this article on Andrew Boyer for the record.
[The information appears at the conclusion of the hearing.]
Mr. Pitts. Without objection, it will be entered into the
record. The chair thanks the gentleman and now recognize the
ranking member of the subcommittee, Mr. Pallone, 5 minutes for
an opening statement.
OPENING STATEMENT OF HON. FRANK PALLONE, JR., A REPRESENTATIVE
IN CONGRESS FROM THE STATE OF NEW JERSEY
Mr. Pallone. Thank you, Chairman Pitts. In 2006, in my
State of New Jersey, a 17-year-old honor student named Rebecca
Lohsen went to the hospital and within days died from a
resistant strain of MRSA. Though her doctors were able to
identify the infection and treat it with the available
antibiotics, it failed to respond to treatment, advancing
rapidly and cutting her life short. And stories like Rebecca's
are all too common and all the more frustrating given the
remarkable advances in American medicine.
The threat posed by antibiotic resistant bacteria or
``super bugs'' is growing, yet the supply of new antibiotic
drugs is dwindling due to drug manufacturers' declining
interest and ability to produce new drugs to meet this threat.
In a CDC report released last year, they find that 2 million
Americans are infected with antibiotic resistant bacteria each
year, and unfortunately, 23,000 will eventually die as a
consequence of their infections. Additionally, 5 to 10 percent
of patients in American hospitals will acquire an infection
during the course of their treatment. And, though the majority
of these infections can be treated, this complicates the
recovery process and ultimately imposes greater costs on
patients and the healthcare system.
Due to the current state of the market, manufacturers are
incentivized to focus their efforts elsewhere, at the expense
of the research and development with new antibiotics to combat
these rapidly evolving strains of bacteria. This reason is why
Congress included many of the provisions of the GAIN Act in the
FDASIA legislation, which was signed into law in 2012. The GAIN
Act was an important step toward solving this problem. Through
GAIN, we are supporting manufacturers in the development and
introduction of new drugs largely through the use of marketing
exclusivities. So far we have seen meaningful progress.
Because of GAIN, FDA has approved a number of new drugs
through the Qualified Infectious Disease Product designation.
With priority review, these drugs are able to combat an
imminent infectious disease threat and reach patients at an
accelerated pace.
However, we should also remember why other laws such as the
Hatch-Waxman Act, are so successful. If Congress decides to
intervene in the market, using the carrot of marketing and
regulatory exclusivities, we should be sure that it achieves
the necessary impact on the pipeline of new drugs to safeguard
the public health.
In pursuit of the greater good, government struck a balance
between the interests of private industry in the public, and
society reaped the benefits. And so that is why I have concerns
about ideas such as transferable exclusivity, the practice of
giving a specified period of exclusivity to a company to use on
any product it wishes as a reward for developing a new
antibiotic. This is a recipe for higher cost drugs with no
direct connection to the cost to developing new antibiotics.
Yet, there are some ideas that are worth further
examination, such as the ADAPT Act introduced by Congressmen
Green and Gingrey. That bill would establish a limited
population approval pathway that would permit FDA to approve
drugs based on smaller clinical trials. So Mr. Chairman, there
are a number of angles the government and private industry can
take to meet this problem head on. I think we all agree this is
an issue which warrants further action, and I welcome the
opportunity to hear from our witnesses today. A special welcome
to Adrian Thomas from Johnson & Johnson, which is headquartered
in my district. I am always pleased to see you represented in
front of our committee.
So I would like to yield the remainder of my time to Mr.
Green.
Mr. Green. Thank you, Ranking Member, for yielding. Few
issues in the public health today are as grave and urgent as
combating the growing threat antibiotic resistance. I am
pleased to learn that yesterday the White House announced the
President's Executive order on the national Combating
Antibiotic Resistance Bacteria, CARB strategy. We need to
control bacteria and carbs, I guess.
Recently, both the World Health Organization and the United
Kingdom joined the United States in recognizing antibiotic
resistance as a global threat. Fighting antibiotic resistance
is both a public health and a national security priority. It is
a threat that I take seriously and believe Congress has a
strong role in answering. The FDA has played a central role in
this important effort, and I thank the agency for their work.
We must all work together to ensure that we have effective
antibiotics for the future.
In 1929, Alexander Fleming invented the process for the
first antibiotic wonder drug, penicillin. Such discoveries for
the 21st century can happen as well if we encourage greater
investment in the development of novel antibiotic drugs.
Antibiotics have saved millions of lives by treating infections
caused by bacteria and made through therapies like surgery,
chemotherapy, and care for neonatal infants possible. By
nature, bacteria evolve and become resistant over time. In
addition, misuse and inadequate diagnosis have contributed to
antibiotic resistance, and most antibiotics are now less
effective or ineffective against infections.
The consequences of antibiotic resistance must not be
underestimated. With each day, many more patients will have few
or no therapeutic options because of the resistance to
available therapies. I thank the chair and ranking member for
this hearing today. Antibiotic resistance and development must
be a high priority for this committee and central to the way we
treat and cure disease in the 21st century. I look forward to
the hearing, and again, I want to thank my colleague,
Congressman Gingrey, for partnering both on the GAIN Act last
Congress and also on the ADAPT Act this Congress, and I yield
back my time. Thank you.
Mr. Pitts. The chair thanks the gentleman and now
recognizes the gentleman from Georgia, Dr. Gingrey, 5 minutes
for an opening statement.
OPENING STATEMENT OF HON. PHIL GINGREY, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF GEORGIA
Mr. Gingrey. Mr. Chairman, I want to thank you. I want to
thank you for calling today's hearing within the 21st Century
Cures Initiative entitled, ``Examining Ways to Combat
Antibiotic Resistance and Foster New Drug Development.'' Let me
first commend Chairman Upton and our colleague from Colorado,
Ms. DeGette, for spearheading this bipartisan endeavor that
really looks at ways we can address emerging challenges in the
healthcare industry.
I have participated in a number of the hearings and
roundtable discussions and have found each to be very
beneficial to all the members of this subcommittee. Mr.
Chairman, we all understand that antibiotic resistant pathogens
are a growing concern not only across the country, but across
the globe. According to the CDC in Atlanta, each year more than
2 million Americans get infections that are resistant to
antibiotics, resulting in the deaths of some 23,000 people and
costing our healthcare system nearly $20 billion in direct
cost, probably $35 billion more in indirect cost, lost time
from work, et cetera.
This year alone, both the World Health Organization and the
U.K. have acknowledged this looming threat. Just yesterday, the
Obama administration took action on antibiotic resistance as
well. Through the signed Executive order, the national strategy
on Combating Antibiotic Resistant Bacteria and the President's
Council of Advisors on Science and Technology, referred to as
PCAST, will be issuing a report, this is an issue that is now
receiving global attention. Unfortunately, though, according to
the FDA, new antibiotic approval has decreased by 70 percent
since the mid 1980s.
A combination of barriers, including, of course, the high
cost of drug development and the small profit margins have
helped to drive companies out of the anti-infectious space to
markets where the return on investment is much higher. You
think of your favorite drug, whether it is for arthritis or
whatever, they simply can make a lot more money and there is a
lot bigger market. These few incentives for companies to
produce new antibiotics have yielded a stagnant research and
development pipeline for antibiotics, and it is ill-equipped to
keep up with the evolving bacterium.
Mr. Chairman, I am glad that Congress has been a true
leader in this arena. With the partnership of my colleague from
Texas, Gene Green, as the other lead author/sponsor of the GAIN
Act, we were able to find a path for this legislation to be
signed into law, and it was, in July of 2012. As many of the
witnesses' testimonies state, the GAIN Act has been an
important step to encourage new development of antibiotics by
focusing on economic incentives to keep companies in the game,
in the market. However, despite these advances, there is still
more work that needs to be done. That is precisely why Mr.
Green and I authored H.R. 3742, the ADAPT Act during this
Congress.
This legislation, a logical next step to the GAIN Act,
develops a new pathway at the FDA for antibiotics aimed at
treating merging threats in limited and high-need populations
when they have no available option at their disposal. The ADAPT
Act will also streamline the process by which the FDA updates
break points information so doctors and medical researchers
have the most up-to-date information in which to expedite the
decisions in the drug approval process.
Mr. Chairman, the model of the 21st Century Cures
Initiative work on the GAIN Act and the ADAPT Act has been a
true bipartisan product, and I commend Mr. Green for his
continued efforts with me on both pieces of legislation.
Earlier this morning, both of us spent an hour on Washington
Journal discussing our efforts addressing drug resistant
bacteria with a sense of comity befitting our committee, and I
think Mr. Green and the moderator and hopefully all the viewers
and listeners would agree with that. And with that in mind, I
look forward to hearing from all of our witnesses today, the
first and second panel.
I had the pleasure yesterday of meeting with Dr. Barbara
Murray, who will be on the second panel, the President of the
Infectious Disease Society of America, and after hearing some
of her anecdotal accounts of life-threatening infections with
her own patients, I am even more motivated to continue the
fight against drug resistant bacteria.
I will give a real quick anecdote, Mr. Chairman. I know I
am running out of time, but my brother is 1 year older than me,
and in 1941, he was sick as a gourd, home with pneumonia, and
the family doctor came to the house and told my parents that he
was going to die unless he gave him a shot of this new
antibiotic called penicillin. And my brother James got that
shot of penicillin and fortunately he lived. Now, there have
been some days since then that I wish he hadn't. He beat me up
every day since then and still does, but that is my own little
anecdote, Dr. Murray.
Mr. Chairman, as we continue with the 21st Century Cures
Initiative, we must work in a bipartisan manner to address this
growing problem across our country. Ultimately, I believe that
the ADAPT Act is the next step in the fight. It is my hope that
we will mark up this legislation during the lame duck session
later next month. Until then, I welcome the testimony that we
will be hearing today to further educate members of the
subcommittee on this critically important issue.
Make no mistake, the cost of inaction in the fight against
life threatening infections is grave, and the CDC has already
provided us with the statistics to prove that. Today's hearing
will serve as a great way to raise awareness on this important
issue.
Mr. Chairman, thank you for allowing me the time normally
reserved for Chairman Upton, and I look forward to continuing
to work with all of my colleagues as this process moves
forward. Thank you for the extra time and being a little soft
on the gavel, Mr. Chairman, as I yield back.
Mr. Pitts. The chair thanks the gentleman and thanks him
for his leadership on this issue.
Now recognizes the ranking member of the full committee,
Mr. Waxman, for 5 minutes for opening statement.
OPENING STATEMENT OF HON. HENRY A. WAXMAN, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF CALIFORNIA
Mr. Waxman. Thank you very much, Mr. Chairman. We held
hearings in this committee in 2010 on the problem of antibiotic
resistance and the fact that it is a growing and dangerous
threat to public health. It is certainly an issue that deserves
the full and complete attention of this committee, so I am
pleased you are holding this hearing. Our overarching goal
should be to ensure that people continue to benefit from these
life-saving treatments, both here and in the United States and
around the globe.
This is an inherently difficult goal to achieve. After all,
when we use these antibiotics, it leads to the development of
pathogens that can no longer be treated by those antibiotics.
Rather than use it or lose it with antibiotics, it is use it
and lose it.
So we are at great risk of losing much of the progress that
has been made in fighting infection and subsequent disease.
Many Americans die or are infected each year from antibiotic
resistant microbes. We pay a high price in other ways as well,
additional hospital stays, hospital readmissions, increased
doctor visits, all add unnecessarily to the Nation's annual
healthcare bill. It will take a multi-pronged approach to
overcome this very serious problem. There is no question that
our arsenal of effective antibiotics is dangerously low today
as a result of antibiotic resistance, so we need to replace
ineffective antibiotics with new ones.
In the 2012 FDA user fee legislation, we enacted a law
designed to create incentives for companies to replace those
antibiotics and develop new ones. That legislation included
provisions from the what was called the Generating Antibiotic
Incentives Now Act called the GAIN Act, and that granted a 5-
year period of exclusive marketing for new antibiotics for
serious and life-threatening diseases.
I look forward to hearing today from our witnesses about
what impact that legislation is having on investments in these
drugs. Exclusivity rewards drug companies by allowing them to
charge higher prices. As a result, it also imposes a
significant burden on patients and on the healthcare system
overall, so we need to approach this particular form of
incentive with great caution.
One bad idea, in my opinion, is the concept of transferable
market exclusivity which is sometimes called the wildcard
exclusivity. This form of exclusivity would give a company that
developed a new antibiotic the ability to transfer a term of
exclusivity to another drug, any other drug that they have, and
this is a hugely costly idea that leads to unfair cross
subsidies. If AstraZeneca were to develop a specified
antibiotic, it could earn a term of exclusivity that it could
transfer to Nexium, a treatment for heartburn which is the
second highest grossing drug last year and earns over $6
billion. Even if the term of exclusivity were just 6 months,
that would result in a reward of almost $3 billion. That means
Nexium patients pay higher prices for longer even though they
may never actually take the antibiotic itself.
As we tackle the problem of antibiotic resistance, we need
to ensure that whatever form the incentive takes, it bears some
reasonable relationship to the amount of the investment the
company is making. I hope we will discuss today another
approach to getting new antibiotics on the market. That is what
has been referred to as the ADAPT Act, or the Antibiotic
Development to Advance Patient Treatment. That bill would
establish a limited population approval pathway that would
permit FDA to approve drugs based on smaller clinical trials.
This is an idea worth examining.
If we do create such a pathway, any drugs approved as a
result would need to be clearly marked with a prominent symbol
to alert providers and patients that the safety and
effectiveness of these drugs has only been assessed on a
limited population. Requiring a designation is integral to the
idea of a limited population approval pathway because providers
have to know that these drugs are to be used only when
absolutely necessary. Otherwise, they will not only put
patients at risk but will contribute to the more rapid
development of antimicrobial resistance to the drugs.
In addition to incentives for developing new antibiotics,
we ought to find ways to cut back on the overuse and misuse of
these drugs. Patients cannot expect to get them every time they
come down with a cold, and physicians should only prescribe
them when they are truly necessary. Perhaps most important, the
indiscriminate administration of these drugs in animal
agricultural operations needs to stop. We should mandate an end
to this practice, but if we cannot take that step, we should at
least have better data about how and where antibiotics that are
important for humans are being used in food animals. We know
practically nothing about this situation.
As a recent Reuters article points out, the data exists in
the hands of major corporations producing these animals. I
would like, Mr. Chairman, another 30 seconds.
Mr. Pitts. Go ahead.
Mr. Waxman. Like Perdue and Tysons, and I have a bill that
would finally give the public access to this information, H.R.
820, the DATA Act. I hope this commonsense bill can be included
in the 21st Century Cures legislation.
I thank the witnesses for being here today and for their
testimony. And Mr. Chairman, I would like to ask unanimous
consent that a statement prepared by Congresswoman Louise
Slaughter be included in the record. She is talking in her
statement about ways to combat antibiotic resistance and foster
new drug development.
Mr. Pitts. Without objection, so ordered.
Mr. Waxman. Thank you, Mr. Chairman.
[The prepared statement of Ms. Slaughter follows:]
Prepared statement of Hon. Louise M. Slaughter
Mr. Chairman, thank you for the opportunity to submit
remarks for the record this morning. I appreciate the attention
being paid to the crisis of antibiotic resistance and the
immediate need to address it. While I appreciate that the focus
of today's hearing is on the development of new antibiotics, I
cannot let the opportunity pass to discuss the overuse of
antibiotics in agriculture and the connection to the
development of superbugs resistant even to some of our last
line of defense antibiotics.
Almost 70 years ago, Alexander Fleming first warned about
the possibility of a post-antibiotic era, warning that--quote--
``the ignorant man may easily underdose himself and by exposing
his microbes to non-lethal quantities of the drug make them
resistant.''
I'm not sure Dr. Fleming could have envisioned that the
biggest threat to antibiotics in the future would come from
factory farms--where 80 percent of the antibiotics in this
country are used in animals that eventually end up on our
dinner plate. His warning rings true today: the daily
distribution of antibiotics in feed and water at sub-
therapeutic levels is creating resistant superbugs, and
destroying the effectiveness of these miracle drugs.
According to a recent report from the World Health
Organization, ``Antibiotic resistance is now a bigger crisis
than the AIDS epidemic,'' and if we do not curb our antibiotic
overuse, ``a post-antibiotic era-in which common infections and
minor injuries can kill-far from being an apocalyptic fantasy,
is instead a very real possibility for the twenty-first
century.'' This would redefine modern medicine. Routine
infections like strep throat could be fatal. A skinned knee
that became infected could become fatal. Life-saving surgeries
like open-heart surgery or organ transplants that require
antibiotics to stave off infection would become too dangerous
for doctors to consider. All of these medical advances would be
thrown away because we are wasting these critical antibiotics
on the farm.
There are those who say there is not a connection between
overuse of antibiotics on the farm and resistant diseases in
humans. I struggle to understand their decision-making process
when the National Antimicrobial Resistance Monitoring System
(NARMS) reports that antibiotic resistant bacteria exist in 81%
of ground turkey, 69% of pork chops, 55% of ground beef, and
39% of chicken breasts, wings and thighs found in grocery
stores. More than 27% of bacterial isolates found on retail
chicken are resistant to more than five classes of antibiotics.
Just this week, the top scientific minds in this country
who make up the President's Council of Advisors on Science and
Technology released their report on antimicrobial resistance
and confirmed what I and over 450 of the leading medial,
scientific and consumer groups in the country who support my
legislation have been shouting from the rooftops for years.
Allow me to quote that report:
``Substantial evidence demonstrates that use of antibiotics
in animal agriculture promotes the development of antibiotic-
resistant microbes in animals and that retail meat can be a
source of microbes, including antibiotic-resistant microbes.
Moreover, antibiotic resistance can spread between microbes
(through the transfer of DNA elements, such as plasmids,
between species) and antibiotic-resistant microbes can spread
from animals to people who come into contact or close proximity
with them. For example, poultry workers in Maryland and
Virginia have been reported to be much more likely to be
colonized by gentamicin-resistant E. coli and are at a higher
risk of infection by multi-drug resistant E. coli than
residents of the community surrounding the poultry operation. A
survey of over 900 adults in Wisconsin and Minnesota found that
drug-resistant E. coli bacteria isolates present in humans were
similar to those in poultry meat, whereas drug-susceptible E.
coli bacteria isolates were not. A study of veterans in rural
Iowa reported that the frequency of resistant Staphylococcus
aureus was 88% higher among veterans living within one mile of
a high-density swine-feeding operation.''
Despite the substantial evidence and despite the nightmare
scenario of a post-antibiotic era, both our federal regulatory
agencies and the Congress are still refusing to acknowledge the
devastating role that antibiotic use in agriculture is having
on the future of medicine in the United States. I am imploring
you today, as you consider the future of antibiotic development
in this country, that you also consider that the routine
overuse of future antibiotics would result in the same
conditions we face today. We must preserve those antibiotics
critical to human health for use in treating disease--not for
growth promotion or disease prevention. Antibiotics are for
treatment of illness--period.
My legislation--the Preservation of Antibiotics for Medical
Treatment Act -would save eight critical classes of antibiotics
for human use while still allowing the treatment of sick
animals. I've carried this bill for seven years now, and I'm
not going to rest until it becomes law. There are too many
lives at stake to give up. We can and must preserve
antibiotics--the future of modern medicine depends upon it.
Thank you.
Mr. Pitts. And I have a unanimous consent request. I would
like to submit the following for today's hearing record. First,
a letter from the Flag and General Officers' Network, an
official 501(c)(19) War Veterans Organization representing
three-quarters of all living U.S. Armed Forces Flag and General
Officers. Secondly, a statement from Cubist Pharmaceuticals, a
global pharmaceutical company headquartered in Lexington,
Massachusetts. And thirdly, a statement from the California
Healthcare Institute, CHI, their statewide public policy
organization representing California's leading biomedical
innovators, over 275 research universities in private, non-
profit institutes, venture capital firms, and medical device
diagnostic biotechnology and pharmaceutical companies. Without
objection, so ordered.
[The information appears at the conclusion of the hearing.]
Mr. Pitts. All members' written opening statements will be
made a part of the record. At this point, we have two panels to
present testimony. On the first panel today, we have again Dr.
Janet Woodcock, the director of the Center for Drug Evaluation
and Research, U.S. Food and Drug Administration. Thank you very
much, Dr. Woodcock, for coming. Your written testimony will be
made a part of the record, and you will be given 5 minutes to
summarize your testimony before questions. So at this point you
are recognized for 5 minutes for your opening statement.
STATEMENT OF JANET WOODCOCK, DIRECTOR, CENTER FOR DRUG
EVALUATION AND RESEARCH, U.S. FOOD AND DRUG ADMINISTRATION
Dr. Woodcock. Thank you, Mr. Chairman, and members of the
committee for holding this hearing on this really important
issue. There is broad agreement that antimicrobial resistance
is a worldwide crisis that is going to require major efforts to
combat. In 2012, the Congress took a significant step in
passing GAIN Act which we have been implementing. In Europe,
the Innovative Medicines Initiative, which is a public/private
partnership launched a major research effort on antimicrobial
resistance. Yesterday, the Administration released a national
strategy for combating antimicrobial resistance. A high level
task force was established by Executive order to carry out and
develop an action plan to carry out the goals.
The strategy is a multi-sector effort to attack this
problem in all its diverse forms by bolstering basic research,
enhancing product development, improving the surveillance,
which has already been alluded to, of resistance and use of
antimicrobials, modifying the use of antibiotics in food
animals, and strengthening international collaboration.
PCAST, which is the President's Council of Advisors on
Science and Technology also released a scientific report and
scientific recommendations yesterday.
Over the past year, the Center for Drugs at FDA has been
very busy on this issue. We have issued many new or revised
guidances on antimicrobial drug development. We approved three
drugs designated under the GAIN Act. We recently cosponsored a
workshop on this topic with the National Institutes of Health.
Of course, our fellow center, the Center for Biologics has been
working on vaccines, another way of addressing this problem,
and the Device Center working on testing methods.
Despite all this progress, we must recognize that a robust
pipeline of new investigational antimicrobials does not
currently exist, nor is there a large number of drug discovery
laboratories out there working to bring forth the next
generation of candidate drugs. So, we don't have a robust
pipeline. The reason for this, apparently, is primarily the
absence of commercial incentives to antimicrobial development.
This problem must be solved one way or another if we are going
to prevail in our fight against the ever-changing microbes.
We don't just need new treatments for resistant organisms,
although we need those urgently, we need to keep introducing
additional treatments against common conditions as well, since
our existing armamentarium is inevitably going to weaken over
time. We don't just need to respond to the current crisis, we
need a robust pipeline going forward.
Because this is such a multidimensional problem, we all
must work together to prevent the loss of these critical
weapons against disease, so I am very happy to answer any
questions.
Mr. Pitts. The chair thanks the gentlelady.
[The prepared statement of Dr. Woodcock follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Mr. Pitts. I will begin the questioning and recognize
myself 5 minutes for that purpose.
Dr. Woodcock, yesterday FDA Commissioner Hamburg posted a
blog post titled, ``FDA's Take on the Executive Order and
National Strategy to Combat Antibiotic Resistance Bacteria''
where she wrote ``Few issues in public health today are as
critical and time urgent as combating the growing threat of
antibiotic resistance. It is a high priority for FDA to work
with our partners to find solutions for this serious public
health problem.''
Would you explain the urgency of this situation for public
health and national security?
Dr. Woodcock. Well, as many of the members have already
stated----
Mr. Pitts. Press your----
Dr. Woodcock. Sorry. As many of the members have already
stated, for public health, we are already seeing excess deaths,
and we are seeing people who in fact cannot be treated with any
existing therapy that we have, and I think the threat here to
public health is that we can have emerging epidemics of these
organisms that they will spread. Right now they are fairly
limited and sporadic, but will spread, and we will be in a
situation where we literally can't treat an infection that is
unfolding in a wider sense.
In addition, each year we are seeing greater and greater
resistance problems for ordinary microorganisms, and so doctors
are having to turn to what we would call second or third line
antimicrobial agents, agents we use to reserve for very
selected situations. And as that occurs, more resistance to
those will evolve, and so eventually we are going to be empty
handed.
Mr. Pitts. OK. In the case of antibiotics, even slight
variations in the bacteria's genetic makeup can be the
difference between a drug working or not working. Understanding
that bacterial resistance compounds this problem many times
over, why is it important for our antibiotic drug pipeline that
we have multiple drug options for the same class or family of
drugs?
Dr. Woodcock. Yes. Well, what we know is when we develop an
antimicrobial it evolves over time after that antimicrobial is
used, and after time, it may be that it can be effective
against certain forms of an organism and not against other more
resistant forms, and the mechanism of resistance is different.
There are many different mechanisms of drug resistance. That is
why having a large number of drugs in a class or even
improvements in a class can be extremely helpful in this
situation because you can match the antimicrobial to the
organism you are trying to treat.
Mr. Pitts. Do we have the type of drug redundancy
highlighted above that we need to effectively combat this
problem right now?
Dr. Woodcock. We do not because that is sort of the cutoff
line. The antimicrobials that are no longer useful against many
infections is getting higher and higher every year, especially
for certain types of bugs.
Mr. Pitts. Do you believe that we need to further
incentivize new drug and diagnostic development if we are to
appropriately address the issue of antibiotic resistance, and
if so, what would you recommend?
Dr. Woodcock. I do believe we must incentivize it because
the current situation shows that the incentives have not been
enough to stimulate development in this area. So for drug
development, apparently, developing antimicrobials is still not
attractive enough. It still doesn't appear that it might not be
a loss to business, that there isn't an attractive enough
business model to build those robust programs that are needed
to both discover and then develop new classes of
antimicrobials.
For diagnostics, I will tell you that Louis Pasteur and
Alexander Fleming would recognize the methods we use today
because they invented them, and so there is a lot of room at
the top for improvement. We are using genetic sequencing of
human genome, which is huge compared to the microbial genome,
but using clinical practice of advanced methods is not the
norm, and that, improving diagnostics would tremendously
simplify clinical trials and also treatment.
Mr. Pitts. Now, we are talking about incentives here. Do
you believe that such incentives could be used in other unmet
need areas beyond just antibiotics?
Dr. Woodcock. Well, of course, I believe that that is
possible. However, as I think Mr. Waxman said, there are
tradeoffs you have to balance. There are always tradeoffs in
putting these incentives in place, and I, being a physician and
a scientist, am not the most qualified person to make those
tradeoffs. I think Congress really has to weigh those.
I can tell you that the public health urgency for this
problem is severe and will continue, and I think you'll hear
that from other experts as well. We are not over the hump here.
We have not succeeded in developing a system that will continue
to generate effective new antimicrobials. We don't have that.
We have sort of heroic efforts here and there.
Mr. Pitts. Thank you, Dr. Woodcock. My time is expired. The
chair recognizes the ranking member, Mr. Pallone, 5 minutes for
questions.
Mr. Pallone. Thank you, Mr. Chairman. Both the Executive
order issued yesterday and the report of the President's
Council of Advisors on Science and Technology emphasize the
danger of antibiotic use in the agriculture industry.
While it is clear we should do more to encourage greater
research in development of new drugs, it also makes sense that
we should be investing in efforts to limit the further spread
of drug resistant bacteria strains and make the best use of
existing drugs so they can remain effective for longer periods.
So Dr. Woodcock, in your testimony, you point to FDA's
cooperative effort with CDC to promote greater stewardship,
including the ``Get Smart'' campaign. I would like you to
elaborate on this partnership, and on FDA's role in the
initiatives laid out in yesterday's Executive order.
Dr. Woodcock. Well, obviously there needs to be better
stewardship both in human and agricultural uses of
antimicrobials, as has already been said. About half, CDC
estimates, of antimicrobial outpatient prescriptions are not
necessary, given the condition the patient has, and that leads,
especially if people only take the drugs for a little bit, can
lead to big problems, and also in the animal world. Now, in the
human area, FDA is collaborating with CDC on these efforts, but
CDC is primarily the lead on improving better use in health
care, and that is a multi-faceted effort.
In the animal health space, FDA had put out a guidance to
the Center for Veterinary Medicine calling on manufacturers to
cease use of important human antimicrobials for growth
promotion in food animals, and they have secured the
cooperation of all the manufacturers who are engaged in that
space, to my understanding, and then there will be a process
whereby those indications are withdrawn. And then use in food
animals would be required under the supervision of a
veterinarian for a health condition in the animal, so that
would be a great improvement.
Also, as was discussed in the report yesterday, though, we
need better surveillance and data to understand the link
between antimicrobial use in animals, or humans, in the
development of resistance. That is still rather poorly
understood.
Mr. Pallone. All right. Thanks. I wanted to get FDA's views
on certain aspects of the ADAPT Act. As I understand the
purpose of the bill, its goal is to facilitate FDA's ability to
approve new antibiotics that have been tested only in a limited
population, and for which the need for the drug is critical. I
know you already do approve drugs tested in limited
populations, for example, drugs for rare diseases, so I would
like you to explain if and why the existing accelerated
approval mechanisms aren't meeting the current need. I would
also like you to address whether you believe the ADAPT Act as
currently drafted provides the FDA with sufficient authority to
ensure that ADAPT antimicrobials would be labeled in a way that
clearly distinguishes them as different from other
antimicrobials.
It seems that if we are considering allowing drugs on the
market tested only in very limited clinical trials, we need to
be confident that providers and patients understand the care
with which these drugs must be used.
Dr. Woodcock. Yes. Well, we think the ADAPT Act has
elements that we have been discussing for a long time. Let me
explain some of the situation. We approve drugs for limited
population all the time, orphan drugs, rare subsets, but
generally speaking, the clinical community is not tempted to
use those for somebody with a cold, right. It is for some rare
enzyme deficiency or some cancer, rare cancer or whatever. With
antimicrobials, the big problem is really the use outside of
where it would really clinically be indicated, and one of the
barriers for these highly resistant organisms is that their
occurrence is sporadic.
We are very lucky that there are not widespread outbreaks,
right, but because there are not widespread outbreaks, it means
the testing of the drugs in broad populations is difficult.
Actually, that is good news because otherwise we would really
be in trouble, all right, if there were large numbers of people
suffering like this.
So that means, by definition, if you are going to get these
drugs on the market for these small populations of resistant
organisms, you are going to have to have small trials, and you
will have more uncertainty about the effects. So more
uncertainty about the effects, and worries that the drug will
be used in conditions where it is not warranted, those are the
two issues we are trying to address.
In orphan conditions, yes, there is uncertainty about the
effects, but the orphan community that uses these drugs,
usually those are sub-specialists who are treating a very rare
disease, and they have a very good understanding of what
studies were done on the drug and so forth. It often may be the
only drug ever studied for that condition.
So our thoughts, and the Administration has not taken a
position on this, but we have thought about this, that to offer
very small development programs is a big incentive, but the
quid pro quo really is to send a signal to the clinical
community, some kind of signal, some kind of message that this
is special. That there is more uncertainty and also use good
stewardship with this particular product because using it in a
lot of conditions where it is not warranted would also more
rapidly increase the development of resistance.
Mr. Pallone. Thank you.
Mr. Pitts. The chair now recognizes the gentleman from
Georgia, Dr. Gingrey, 5 minutes for questions.
Mr. Gingrey. Mr. Chairman, thank you for recognizing me. I
know that the vice chairman of the subcommittee, my colleague,
Dr. Burgess, was scheduled to go next, and Mike, thank you for
letting me ask my questions now.
Dr. Woodcock, thank you, too. As a witness, we have had you
before our committee many times since I have been on the
committee, and you are just always so straightforward and you
explain things in a very clear way, and I mean that sincerely.
You do a great job, and we appreciate that very much.
I want to continue in the line of questioning that Mr.
Pallone started, and again, I have limited time, so let me get
right into that. Congressman Green and I had been working on
this ADAPT Act, as you know, and it is legislation that
supports the FDA's flexibility to consider all forms of
evidence in addition to data from clinical trials when
considering novel antibiotics.
How important do you believe adaptive and unique trial
designs can play in encouraging new antibiotic drug
development? And before you answer that part, and I am sure
everybody in the hearing probably knows this, but in your
typical phase 3 trials before a drug can get to market, you are
going to have to have a population of 1,000 or more people that
you are treating, and there are also other requirements that
they can't have had an antibiotic within 24 hours of the start
of the trial, or at one point it was 3 days, I think, and then
we got it down to 24 hours.
But you are going to have a limited population of people
that have these diseases, and when they get to the hospital
sick as heck, the first thing the doctor is going to do, the
emergency room physician is going to hang some antibiotic, even
if it is wrong, they are going to start treating them, and
then, all of a sudden they are not eligible, and you have a
limited number of people. If you wait till you get 1,000, it is
too late. So if you will kind of take that a step further and
discuss that for us.
Dr. Woodcock. Thank you. And thank you, and Mr. Green, for
your leadership on this. I think it is very important.
Yes, there is a range, and I think that is what people have
to recognize. There is a range of development programs that are
needed. For common conditions, outpatient pneumonia, we have a
lot of drugs out there that still work. If we introduce new
drugs, we want them to be just as good as the other drugs, and
they are going to need larger development programs, and that is
true for many. But for these very rare, fortunately, resistant
organisms that are multi-drug resistant, there is almost
nothing to treat them. These cases are occurring sporadically
here and there or in outbreaks in ICUs or something like that,
and we have to think of different ways of evaluating new
treatments. We can't just set up a trial and wait for all this
to happen and expect we will be able to enroll thousands of
people. And it is true, in fact, if we enrolled thousands of
people, it will have been too late, this would be a terrible
thing.
So it is true that all antimicrobial drug development is
very difficult. In addition to the economic problems, there is
this huge difficulty in doing trials, especially in people who
are really sick. You can't use a placebo, obviously. You don't
know, because of the problem with diagnostics, you may not know
for a few days what organism they are infected with. So there
are all these technical problems that make it very difficult to
do antimicrobial drug development.
So because we have a tremendous unmet medical need for
people--where there is no treatment available, typically what
we do in that case is we accept more uncertainty, and that
means novel trials that we might do.
Mr. Gingrey. Dr. Woodcock, speaking of that uncertainty, I
think that is probably why, and I commend the President for
this in his executive order of just yesterday, the $20 million
award for the development of these point-of-care diagnostics so
someone could take a pill or a piece of tape or something and
put it inside their mouth. If it turns a certain color, you
know what you are dealing with right there, and you don't have
to just shotgun approach.
Dr. Woodcock. That is right.
Mr. Gingrey. You can immediately go right to what you need,
so I think it is a great thing.
Dr. Woodcock. I agree. I mean, if we could bring diagnosis
of infectious disease into the 21st century, we would have made
a huge advance and really accelerated the development of
therapy, so that is a good thing.
Mr. Gingrey. Thank you very much, Mr. Chairman. I yield
back, and thank you for your courtesy.
Mr. Pitts. The chair thanks the gentleman. Now recognize
the ranking member of the full committee, Mr. Waxman, 5 minutes
for questions.
Mr. Waxman. Thank you, Mr. Chairman. I also want to say to
you, Dr. Woodcock, this may be the last hearing where you and I
will have the opportunity to publicly talk like this, but you
have done a wonderful job at the FDA, and your responses to
questions from both sides of the aisle have been very, very
thoughtful, and I want to commend you for the work you have
been doing and thank you for it.
I want to echo the comments by Mr. Pallone about the
importance of strong labeling statement or logo in the context
of the ADAPT Act. I think it is essential that the drug bear a
prominent statement describing the abbreviated pathway by which
it came to market. Without this requirement, I am not sure that
the whole thing would work. It would be much less likely to
achieve its purpose of fostering and facilitating the
development of critical new antibiotics for life-threatening
resistant pathogens. And additionally, inappropriate or
injudicious use of a drug developed through this pathway could
result both in patient harm and in more rapid loss of the drug
to antibiotic resistance, so I just wanted to underscore that
point.
I want to ask you about a concept that you mention in your
testimony designed to spur development of new antibiotics. That
is delinkage. As I understand it, under this model, the sale of
antibiotics would be delinked from the returns on investment.
After all, we don't want to say that we want more antibiotics
sold. We want to make sure that the antibiotics that are sold
and used are antibiotics that are going to stay effective for
as long as possible.
So some other funding mechanism would be created besides
the traditional way of selling more drugs to ensure that a
company was able to make a profit from developing an
antibiotic. As others have noted, the usual pharmaceutical
business model doesn't fit very well in the case of
antibiotics.
We need to, however, recognize companies need to be able to
recoup their investment and make a reasonable profit. Others
have raised the notion of a wild card exclusivity. I mention in
my opening statement I think it is a very dangerous idea. We
don't want to force patients taking one type of drug to fund
development of another, so ensuring that antibiotic developers
still can make a profit without linking that profit to how much
antibiotic is actually sold seems like a brilliant way to
approach this problem. Could you elaborate on this, tell us
more about what ideas you have along these lines?
Dr. Woodcock. Well, yes, because right now we have
incentives that actually weigh against our objectives. Our
objectives are that we have the most judicious use of new
antimicrobials possible, and yet the incentive, if you have
spent $500 million developing the drug, you need to recoup that
amount of money and a fair profit to stay in business and
develop the next generation. And so these incentives are
sideways to each other and countervailing, and so that is one
idea that has been raised that we mentioned to delink the need
to have a large volume of the antibiotic used which would then
lead to faster development of resistance. So if that were
delinked from the----
Mr. Waxman. Do you have ideas on how to do that?
Dr. Woodcock. I, as I said, I am really not good at
financial matters, and so I am sorry.
Mr. Waxman. We could count on you for everything, economic
advice as well as pharmaceutical and food and other things that
FDA does.
Well, let me talk to you about another issue and that is in
stewardship, using antibiotics judiciously. It seems to me this
is a critical component of any effort to address the antibiotic
resistance problem. The just released report on Combating
antibiotic resistance from the President's Council of Advisors
in Science and Technology, or the PCAST, stresses the
importance of increasing the longevity of current antibiotics
by improving the appropriate use of existing antibiotics and it
discusses the need to look at both human use and animal use of
existing antibiotics.
We know there is a lot of inappropriate use of antibiotics,
both on the human side and I believe on the animal side. The
PCAST report describes the important role that diagnostics can
play in reducing this type of inappropriate use. Do you agree
that diagnostics are important for stewardship efforts? And you
alluded to this earlier, but can you describe how the
widespread adoption of diagnostic tests would help preserve
existing antibiotics, and is FDA taking any actions to foster
the development in the use of these tests?
Dr. Woodcock. Well, I believe diagnosis should be the
foundation of therapy, and unfortunately, in the infectious
disease space, often you are treating well before you know or
before you ever know what the person has, and this is a
fundamental problem. Like I believe the advent of rapid strep
testing has really reduced the use of drugs for presumptive
strep that often is colds or something, upper respiratory
infections of one sort of another.
So if we could get more certainty into the diagnosis early,
be able to reassure the doctor and the patient or family that,
no, this is not a dreaded bacterial infection that needs an
antimicrobial, we could go a long way, I think, to lowering
this inappropriate use. So diagnostics are the key. It is just
we are far away from that right now and need to stimulate that.
Mr. Waxman. Give more incentives for that?
Dr. Woodcock. I believe so, uh-huh.
Mr. Waxman. Thank you. Thank you, Mr. Chairman.
Mr. Pitts. The chair thanks the gentleman. Now recognizes
the vice chair of the subcommittee, Dr. Burgess 5 minutes for
questions.
Mr. Burgess. Thank you, Mr. Chairman. And Dr. Woodcock,
again, welcome to our humble little subcommittee. Your last
statement, diagnostics are the key, now, this is not part of
this discussion today, but we have had discussions on
diagnostics, and I realize it is not your part of FDA that is
talking about increasing the regulation of testing,
particularly laboratory diagnostic tests, or laboratory
developed tests, rather, but that that factors into the
equation. I mean, yes, we are talking about the length of
drugs, of time it takes drugs to get through the pipeline, but
if it also takes the testing longer to get through the
pipeline, we are actually making things harder on ourselves,
are we not?
Dr. Woodcock. Yes. Well, recently, for example, we have had
a workshop with Brookings on this issue of the co-development
and the technical issues. On the final guidance that we put out
recently on co-development and companion diagnostics said for
life-threatening disease, we are going to go ahead and approve
the drug even if the test isn't fully baked yet.
There are technical problems in getting these tests
developed right now, and I think all of us believe that for
many of the genomic tests, that next generation sequencing is
really going to be a key and really rapidly improve this
situation. So I have great hope that that will be coming soon
because we are facing it now. Every disease--say cystic
fibrosis, for example, there are 150 different mutations in
that gene, each of which may translate to a slightly different
phenotype in prognosis, and that goes with cancer and many
other diseases. We really need to rapidly get to a point where
we have a true standard that we can all agree upon so that we
know what we are dealing with, and that, yes, that will rapidly
improve development of drugs for these serious conditions.
Mr. Burgess. Well, I share your enthusiasm for genomic
testing. I am somewhat more pessimistic because it seems like I
can remember Dr. Elias Zerhouni in my first term on this
committee, which was many, many years ago talking about some of
these same things and where it is sort of the Jetson's flying
car. We are still waiting for that to happen.
On the issue, and at HHS, you did your study on antibiotic
initiatives, the incentives for development of new drugs,
vaccines, and rapid diagnostics for bacterial disease, and then
talked about moving the needle in monetary terms for companies
by a reduction of the time for clinical trials, correct?
Dr. Woodcock. Yes.
Mr. Burgess. Is it really possible to move the needle on
that?
Dr. Woodcock. Well, I believe for the limited population
antibiotic development use that is possible. That is only one
factor, but if you have a very high bar to getting on the
market, then you are going to need much stronger incentives. I
believe for those very rare, right now, resistant organisms, we
could have very small development programs and that there be a
societal agreement that having a treatment available for those
is better than having nothing. And so we could have very small
development programs.
We simply would like to have a signal then to say to the
clinical community, ``No, that this is different, OK. No, this
didn't have a huge development program. We are offering you a
tool, but you ought to be aware and provide good stewardship of
this tool.'' So we do believe in most cases it is possible, and
even for common diseases, we have worked with new guidances to
try to lower the cost of a development program so that the
pipeline can be, you know, more robust.
Mr. Burgess. On the issue of judicious use and stewardship,
and I hear the birds that are set on that, but when you talk
about using things outside their area of indication, we tend to
think of the world in which we live, but I am from Texas, and
just a little bit south of Texas there is a different world
where there is not a prescription required and people can
simply go to the farmacia and say I need this----
Dr. Woodcock. Right.
Mr. Burgess [continuing]. And the pharmacist may direct
them to a particular drug or they may just simply come in with
a recommendation from a family member and make that purchase.
So it is obviously harder to control that within the
jurisdiction of the United States when it is happening right
outside; is that not correct?
Dr. Woodcock. I totally agree. Everywhere is right outside
with modern air travel, and so we are getting soldiers back
from combat who have acquired very dire resistant infections.
We have travelers who are coming back in the United States who
have been in--there are many countries where antimicrobials are
used very freely and may be available to consumers without
intermediaries.
Mr. Burgess. And it concerns me that we want to put the
onus on the doctor treating the patient in an emergency room
with a sick kid and a concerned family, and we are putting all
the onus on our physician here when the greater wide world none
of those constraints exist. I agree with labeling. I agree with
making the indications well known, but I don't think we should
ever try to put the Federal Government in the position of
second guessing the judgment of a physician.
Dr. Woodcock. Well, we agree with that. Because treatment
is empirical, we can't indicat. It has to be suspected. You
can't say you can't treat a patient because this wasn't studied
in clinical trials if there is nothing else available, or if
clinicians, as you said, must use their best judgment when a
patient presents before them. We agree with that. We want to
give the best directions and information to the clinician so
they are aware of not only what clinical situation they are
dealing with but how much information pertains to the drug and
what kind of drug it is.
Mr. Burgess. Thank you, Mr. Chairman. I will yield back.
Mr. Pitts. The Chair thanks the gentleman.
Now, recognize the gentleman from Texas, Mr. Green, 5
minutes for questions.
Mr. Green. Thank you, Dr. Woodcock, for being here this
morning. It is always a pleasure to have you before our
subcommittee.
I want to commend you and the FDA on the efforts on the
GAIN Act. I know at least two drugs have been released, and I
also want to thank you for your efforts on the ADAPT Act
legislation I cosponsored with my colleague and good friend,
Dr. Gingrey.
When Dr. Hamburg participated in last week's Cures round
table, she spoke about the troubles with large clinical trial
designs in the antibiotic space.
Can you tell me your thoughts on how the unique nature and
incentives, or even disincentives, inherent to the antibiotic
space can sometimes make large clinical trials prohibitive?
Dr. Woodcock. Certainly. Well, not only is it actually kind
of hard to discover new antibiotics, it is expensive to develop
them, and the reason is you have a--it is really what Dr.
Burgess was talking about. You have a patient before you with
pneumonia. They could have all sorts of different organisms
causing the pneumonia, and without rapid diagnostics, you don't
know what is causing the pneumonia.
And so when a physician is trying to use an investigational
drug, you have a sick person in front of you, you have a
prolonged consent process where you have to have informed
consent; people are not going to wait, often, to go through
that process to start a sick person on antibiotics.
And so then we have the issue that the patients are
pretreated with different therapies until they get into the
clinical trial, and then you have all the heterogeneity, and
then you have existing therapies. It is not ethical to have the
comparison group have no treatment usually. And so you have to
compare it. You have to do a comparative trial against existing
therapy. Those are typically called non-inferiority trials
because you may not expect to be better than existing therapy;
you simply want to show you're statistically as good as.
So those challenges tend to increase the number of people
needed to be enrolled in a clinical trial to a very large
number, and they are hard to get. They are hard to enroll
because clinicians often don't want to take sick people and go
through all the paperwork to get them in a clinical trial.
Mr. Green. OK.
The ADAPT Act envisions a scenario where more adaptive
clinical trials may be used to help drug developers seeking to
create the next antibiotic effective against drug-resistant
bacteria.
Can you tell me your thoughts on how the pathway laid out
in the ADAPT Act may benefit drug companies in pursuit of these
new and novel antibiotics?
Dr. Woodcock. Yes. Well, we envision that you can make
trade offs based upon the medical need, and we do this in many
cases. So if you have a tremendous medical need, people are
going to die quickly, and you have nothing to treat them with,
then you will accept a lot of uncertainty about the estimates
around safety and effectiveness in exchange for something that
may work for that patient. Right? And so that means you can
have shorter, very small development programs, if the need is
huge.
On the other hand, if we are talking, for example, about
another drug to treat pneumonia, which is a more common
infection for which therapies are available, that situation
would not be covered by the ADAPT Act. With ADAPT we are
talking about rare resistant organisms where there are really
very few treatment options available. And we actually think
there are multiple development programs that could be done,
depending on this level of need.
In some cases, you may only have ten infections in the
United States a year of this certain organism. In other cases,
you may have hundreds. You could get a more robust program
there, right? But then you are going to be exposing more people
when you approve the drug because there are hundreds of people,
maybe thousands of people, out there that have the condition.
So you would basically match the development program and
the medical need together and put that together, but then we
would like to have a very strong signal or symbol or whatever,
not of a fearful signal or whatever, but an informative signal
to the clinician that the drug had gone through this kind of
development pathway so they would understand that.
Mr. Green. Thank you.
And I hope with this hearing today and we will be able to
move the ADAPT Act across the line in the future.
In the coming weeks and months I expect to continue our
dialog with interested parties and stakeholders, including our
second panel today, on ways to strengthen this proposal and
complete the next step in fighting our public health crisis.
I want to thank you and your staff for your hours you have
spent working with our offices during the August recess, and I
know we can continue that effort because this is important. And
again, thank you for being here.
And I yield back my time, Mr. Chairman.
Dr. Woodcock. And I thank you for your leadership.
Mr. Pitts. The chair thanks the gentleman.
And now recognizes the gentleman from New Jersey, Mr.
Lance, 5 minutes for questions.
Mr. Lance. Thank you very much, Mr. Chairman.
Good morning to you, Dr. Woodcock.
Dr. Woodcock. Good morning.
Mr. Lance. As members of the committee, we have heard
firsthand the urgent need for greater incentives to encourage
new drug and diagnostic development in the antibiotic space.
Some of the witnesses on the second panel have recommended
a wide range of incentives that would encourage greater
development.
Do you believe that incentives we identify in the
antibiotic space might also benefit other areas of unmet need
such as rare diseases?
Dr. Woodcock. Well, as I said earlier, I believe that there
is a tradeoff between the incentives you offer. There is always
some tradeoff there, and there are various orphan diseases for
which there are many, for which no development is occurring. So
I think you have to determine whether, those tradeoffs, those
economic tradeoffs and I am not qualified to say what is the
right course. I think that Congress makes those decisions.
However, I can tell you that antimicrobial development is
urgent and it is a public health issue. The orphan drugs, those
people are suffering from those, have a tremendous need for
therapies to be developed, and few are being developed.
We are doing some things such as working with the National
Organization for Rare Diseases to get better natural history
studies that will incentivize development and make it easier to
understand what is the course of this orphan disease so we
understand what is needed to study it. However, there are still
major financial obstacles.
Mr. Lance. Thank you.
As you know, I chair the rare disease caucus on the
Republican side, and I have in my office virtually every week
parents of children who suffer from rare diseases where there
are no medicines at all, and as a society, we have to do a
better job, and I have read the testimony of those on the
second panel, and I hope we can move forward.
And you say you may not be qualified, but I think you are
one of the great experts in the country on all of these issues,
and we look forward to working with you in that area.
Yesterday the President announced an executive order on a
five-year plan to combat antibiotic resistance. What role, Dr.
Woodcock, will the FDA play in helping to facilitate the
President's order?
Dr. Woodcock. Yes. Well, we have been working with the
planning group on this, and the FDA has a wide range of
responsibilities, everything from animal health and those
issues, the surveillance activities which are done of
antimicrobial resistance, for which CDC is the primary lead,
but FDA, for example, works with CDC and USDA on the National
Antimicrobial Resistance Monitoring System, NARMS, which is
mentioned in those reports which monitors antimicrobial
resistant organisms in foods and so forth, and these things are
intended to be strengthened.
In addition, we will work on redoubling our efforts to
streamline antimicrobial development from a regulatory
perspective, and obviously there is interest in better
diagnostics which is put forth in that report. So we have
multiple roles to play.
Mr. Lance. Thank you.
And finally, Dr. Woodcock, may Bucknell win all of its
games in football this autumn except, of course, against
Lehigh.
I yield back the balance of my time.
Dr. Woodcock. Thank you.
Mr. Pitts. The chair thanks the gentleman.
Now recognize the gentleman from Illinois, Mr. Shimkus, 5
minutes for questions.
Mr. Shimkus. Thank you, Mr. Chairman.
And, Dr. Woodcock, it is good to see you back here again,
but I think you are being too coy. The business model to
whether it is going to be in diagnostics or testing is the same
business decisions that we make in our home. It is simply about
risk and reward, and so what is the reward that will encourage
them to stay and what is the amount of risk, and I think you
all are going to play a big role in that, and we would hope you
will work with us to do that.
I have been very excited about this debate of the
diagnostic space, and in your opening statement, and I had to
go onto the World Wide Web. All new technology allows us to do
that without telling staff to go find it and then get it back
to us.
Fleming was born in 1881. Pasteur was born 1822.
Dr. Woodcock. Right.
Mr. Shimkus. Surely if they could recognize our testing
procedures now, we have got work to do to ramp it up, I think,
and that is the whole biosimilar debate and the genetic
markings and all this other genome stuff that is going on. So I
am very, very excited.
Also I have been involved and helped along with following
Dr. Gingrey's lead. Appreciate the work he has done. And Gene
Green, I look forward to working with Gene as we move forward
in the next Congress, and we are having discussions to do that.
So you hear the same questions right from us? And so I
think what we really want to do, and we will hear it from the
next panel, is let's get a handle on this risk and reward, and
I am not so adverse to incentivizing the private sector in
something that they are moving on that is going process and
helping them do that if then they are going to take and then go
in places that no one else is going to go.
So one of the first questions was, as you have seen of
companies leave the field of antibiotics, are they small,
medium, or large? How would you classify them?
Dr. Woodcock. Well, I would say that the larger companies,
most of them have left the area for better pastures, so to
speak, where they see a business model that provides a return
on investment, and similar with many of the medium companies.
There are many small startups that are trying to get into
the antimicrobial space and that is good news, but I must
recognize they aren't always as successful and they may only
have one product that they are trying to develop.
Mr. Shimkus. So, and we have talked a lot about the ADAPT
Act today, and there has been some success in that process.
Do you think there are some additional things we can do to
incentivize? What other things can we build on to encourage
additional incentives for the ADAPT Act or other processes that
we are talking about?
Dr. Woodcock. Well, I think you have to think about what
are the alternatives. All right? I know there is some
government development--there are government awards. Those are
usually under contract. They are for certain entities--
molecular entities.
So there are a few of those, but what are the other ideas
to develop a robust--you need drug discovery effort, and that
means scientists working full time in laboratories trying to
figure out the new molecules. This is way before a drug gets
tested in people, and it doesn't really involve the FDA, and
what I understand from the community, the discovery community,
is actually antimicrobial discoveries are quite hard.
And I didn't know that until I talked to them, that they
have screened large numbers of molecules and pathways and so
forth, and it is harder, it is hard to find the next generation
of products. And so that means a very robust scientific effort
has to go on in the basic science of microbes and also in
discovery of these new molecules, and to do that, somebody has
to have the faith that they are going to make money from that
10, 15 years hence. OK? And they don't have that faith right
now, I can tell you.
So I don't think whatever has been done is enough. And
because you have to consider, if it is not going to be
commercial development, how is it going to happen? Where is it
going to happen?
Mr. Shimkus. And would help us as we go through this
process, help this committee to identify ways that we can help
incentivize?
Dr. Woodcock. Absolutely.
Mr. Shimkus. I mean, because you are talking with these
folks. And we will too, but we will need a lot of ears on it.
And I am going to end just with this, this labeling debate,
the way I understand it. We went through this debate with the
paper labelings and the information on pill bottles that no one
reads. Everybody knows that. So labeling through the Web and
labeling through--there has got to be a better way than just to
keep putting stickers on pill bottles or things, because they
are just overwhelmed, and I would like some simplicity in that.
That is just a statement.
Dr. Woodcock. Could I respond to that?
Mr. Shimkus. Please do.
Dr. Woodcock I think the FDA--CDER is working on developing
a patient information leaflet. All right? A one-pager that you
get either electronically or at the pharmacy that tells you--
every other country has this kind of thing. OK? So it tells you
how to take the drug, what it is for, and so forth.
But then we have proposed and we are interested in going to
an electronic physician label which is that thing that is
folded up inside the pill box. We would like to move that to
electronic with some paper options for those who are still
electronically impaired, shall we say.
But most of the world can easily get that information at
Drugs@ FDA, and many other sites.
Mr. Shimkus. Thank you.
Mr. Pitts. Chair thanks the gentleman.
And now recognize the gentleman from Florida, Mr.
Bilirakis, 5 minutes for questions.
Mr. Bilirakis. Thank you, Mr. Chairman. I appreciate it.
And thank you for your testimony, Dr. Woodcock. We
submitted some questions for the record in November, and to my
knowledge, the committee hasn't received many responses. So I
want to ask you one question again.
Can you tell me how many treatments were approved with
novel biomarkers used for the first time within the last 5
years? Have any accelerated approvals occurred with a novel
marker and a never before treated disease within the last 5
years? How many new biomarkers did the FDA accept for first
time use in the last 5 years? If you can provide that answer.
Dr. Woodcock. Yes. We are working very hard on this. That
was a very provocative question and, actually, we had a very
long debate last week among our senior people on the definition
of a biomarker, and which of these end points, such as FEV1,
which is how fast you can breathe into one of those machines,
is that a clinical end point or is that a biomarker? Clearly,
in my opinion, it is a biomarker, but not everyone agreed with
that. So we are working very diligently on that.
The answer is yes. We approve a large number of drugs on
biomarkers end points all the time. A very significant
proportion of the drugs we approve are based on that, and we
have approved novel ones in the last 5 years, but to get you
the count has taken a little bit more effort because we had to
resolve these definitional issues, disputes with that.
Mr. Bilirakis. When do you think we might get some answers
with regard to the count?
Dr. Woodcock. I am not in control of that time frame, but I
can tell you we are working very diligently, and I believe you
will get this response.
Mr. Bilirakis. OK. Well, continue to follow up.
Dr. Woodcock. It was a good question. It really provoked
some thought internally.
Mr. Bilirakis. Thank you.
There was approximately $450 million in direct funding in
Fiscal Year 2014 to address the antibiotic crises. These funds
were allocated across HHS, the VA, of course, DOD, and USDA.
About 75 percent was used for basic and applied research with
the rest directed toward stewardship and surveillance.
Currently how do these various agencies coordinate their
efforts?
Dr. Woodcock. Well, there has been a longstanding
antimicrobial task force at the agency level across the
government that was headed at HHS, and FDA has been a part of
that.
The Executive order conceives and directs formation of a
higher level task force in the government that will direct the
implementation of the strategy that was announced.
But there has long been coordination across the government
agencies, and I believe the PCAST report discusses that.
Mr. Bilirakis. OK. On this how is the U.S. coordinating
with the World Health Organization and other organizations as
well as other countries working to combat antibiotic
resistance?
Dr. Woodcock. Yes. We do have, we, the FDA, CDC, and many
others have relationships withthe World Health organization,
and I think the Executive order yesterday and the strategy
conceives of much tighter collaboration with WHO in a very
concerted way.
Mr. Bilirakis. OK. Thank you very much.
And I yield back, Mr. Chairman. Appreciate it.
Dr. Woodcock. Thank you.
Mr. Pitts. Chair thanks the gentleman, and now recognize
the gentlelady from Colorado, Ms. DeGette, 5 minutes for
question.
Ms. DeGette. Thank you very much, Mr. Chairman.
I think this has been an excellent discussion, and I just
wanted to ask you to clarify one thing, Dr. Woodcock.
Mr. Outterson on our next panel is going to talk about the
report on initiatives by the Eastern Research Group, and what
that report concludes is that shortening clinical trial time
frames is an unlikely contributor to innovation.
We have been hearing counter arguments to this that without
something like the approach taken in the ADAPT Act that I am a
cosponsor of, it just isn't feasible to do clinical trials on
drugs intended to treat the most serious and resistant
pathogens.
So from that perspective, ADAPT might be considered a
necessity but not a sufficient condition for developing the
most needed antibiotics, but also it would need to be paired
with other incentives to spur investment in that area.
So I am wondering if you can just spend a minute giving us
your views on this issue because, really, it seems to go to the
heart of whether we should even go forward with the ADAPT Act?
Dr. Woodcock. Well, clearly there are multiple barriers to
antimicrobial drug development for antimicrobial resistance. I
do agree that the streamlining of clinical trials for testing
drugs that treat resistant organisms will stimulate development
in that area. Why? Partly because developers have told me that.
But two, because we know from experience that if we have a
clear path to market and people understand it, they are willing
to put their money down, betting that they will have a molecule
that can get approved.
But this is clearly not sufficient. Number one, we are only
talking about the most resistant organisms here and a small
cadre of drugs to treat them.
We also need a robust pipeline of discovery that will lead
to new drug candidates for all different kinds of infections.
So the limited population antibacterial drug idea and the
streamlining of clinical trials, which wouldn't just decrease
the time frame, it would also decrease the cost and the number
of people needed. So it would do a number of things.
That is one thing that we can do at FDA that we think would
be beneficial and would be beneficial for patients, but it is
not going to fix this problem we have of investment.
Ms. DeGette. Thank you.
Mr. Chairman. I yield back.
Mr. Pitts. I think that concludes this round of
questioning. We will have follow-up questions, I am sure, from
members. We will send them to you and ask that you please
respond.
But, again, Dr. Woodcock, you are a terrific witness. Thank
you for your being so forthright and clear in your answers.
And we will now take a 3-minute recess as we set up for the
second panel.
Dr. Woodcock. Thank you.
[Recess.]
Mr. Pitts. The subcommittee will reconvene on our second
panel.
Today we have and I will introduce them in the order that
they will make their presentations.
First, Dr. Kenneth Hillan, Chief Executive Officer of
Achaogen; Dr. Barbara Murray, President, Infectious Disease
Society of America; third, Dr. Adrian Thomas, Vice President of
the Global Market Access and Global Public Health, Janssen
Global Services; and then Mr. Kevin Outterson, Professor of
Law, Boston University School of Law; Mr. Allan Coukell, Senior
Director, Drugs and Medical Devices of the Pew Charitable
Trust; and Dr. John Powers, Assistant Clinical Professor of
Medicine, George Washington University School of Medicine.
Thank you all for coming. Your written statements will be
made a part of the record. You will each have 5 minutes to
summarize your testimony.
And we will begin with Dr. Hillan. You are recognized 5
minutes to make your opening statement.
STATEMENTS OF DR. KENNETH J. HILLAN, CHIEF EXECUTIVE OFFICER,
ACHAOGEN, INC.; DR. BARBARA MURRAY, PRESIDENT, INFECTIOUS
DISEASE SOCIETY OF AMERICA; DR. ADRIAN THOMAS, VICE PRESIDENT,
GLOBAL MARKET ACCESS AND GLOBAL PUBLIC HEALTH, JANSSEN GLOBAL
SERVICES, LLC; KEVIN OUTTERSON, PROFESSOR OF LAW, BOSTON
UNIVERSITY SCHOOL OF LAW; ALLAN COUKELL, SENIOR DIRECTOR, DRUGS
AND MEDICAL DEVICES, THE PEW CHARITABLE TRUSTS; AND DR. JOHN H.
POWERS, ASSISTANT CLINICAL PROFESSOR OF MEDICINE, GEORGE
WASHINGTON UNIVERSITY SCHOOL OF MEDICINE
STATEMENT OF DR. KENNETH J. HILLAN
Dr. Hillan. Thank you.
Good morning and thank you, Mr. Chairman and members of the
committee for inviting me to testify today.
It was also heartening to hear the recognition of the work
of Alexander Fleming, my fellow countryman. Of course not only
did he discover penicillin, but actually when he received his
Nobel Prize, he also spoke of the danger of the ignorant man
who may easily underdose himself by exposing the microbes to
non-lethal doses, make them resistant. That was back in 1945.
I am the chief executive officer of Achaogen, a company
focussed on discovery, development, and commercialization of
novel antibiotics for multi-drug resistant gram-negative
infections.
It is a small company with fewer than 50 full-time
employees and is based in the San Francisco Bay area. We are a
member of the Antimicrobial Innovation Alliance, a coalition
created to address the unique challenges that we have heard
about today.
As you have already heard, antibacterial resistance is one
of the most significant medical challenges our country faces
today, and at Achaogen, we are committed to trying to find
solutions.
Our lead product candidate, plazomicin, which has been
engineered specifically for multi-drug resistance is currently
being evaluated in phase 3 clinical trial in patients with
bacterial infections caused by carbapenem resistant
Enterobacteriaceae, and the carbapenems are considered to be
our last line of antibiotic defense in settings where
antibiotics are no longer active.
The phase 3 trial utilizes a superiority designed to
demonstrate a reduced number of deaths in patients treated with
plazomicin based therapy versus the best available standard of
care, which, unfortunately, is not very good today.
We have also developed the diagnostic assay that has being
used in the phase 3 trial to measure plazomicin blood levels to
try to help to individualize dosing for patients which we
believe will improve outcomes.
The innovative design and incorporation of the diagnostic
assay required close consultation and coordination with both
the drug and diagnostic branches of the FDA, and we find our
interactions with the agency to be extremely collaborative and
believe this approach serves as a model for how the FDA can
help to facilitate companies with development of antibiotics in
settings of urgent unmet medical need.
The plazomicin program is also benefited by receiving the
first contract awarded through the Broad Spectrums
Antibacterial program from the Biomedical Advanced Research and
Development Authority, also known as BARDA, and this contract
is designed to advance plazomicin through approval by the FDA
and could provide over $100 million in total funding.
However, even with plazomicin in a groundbreaking phase 3
study, a great team back at Achaogen, and exciting early stage
pipeline, a successful IPO, and significant government
investors aboard, it has not been easy, and there remains
significant barriers for companies developing antibiotics, and
we can and must work together to address these obstacles so
that effective antibiotics will always be available for
patients.
We would like to propose significant changes in four key
areas.
First, we believe new economic incentives are key. There is
a need for reimbursement reform for antibiotics and for
additional incentives, both push and pull mechanisms. The
economics of developing new antibiotics is not currently
attractive to the pharmaceutical industry, and many leading
companies have exited from the antibiotic space. This has lead
to a decline in the number of new antibiotic approvals, and has
heralded the increase in antibiotic resistance.
Commercial returns for an antibiotic are limited by the
fact that generic antibiotics are cheap. New antibiotics are
used sparingly to preserve their use. Reimbursement at
hospitals is limited to a fixed payment system that is intended
to cover the total cost of patient care, and because longer-
term returns are eroded by the unavoidable development or
resistance.
Furthermore, other therapeutic areas such as oncology or
diabetes provide pharmaceutical companies with much more
attractive opportunities for a return on their investment.
We believe the DISARM Act sponsored by Congressman Pete
Roskam and Danny Davis has been proposed for reimbursement for
qualifying antimicrobial products in a hospital setting. We
belive this would provide a powerful incentive as currently the
payment to the hospital is the same regardless of the price of
the antibiotic. So hospitals are incentivized to use the
cheapest but not always the best and most effective antibiotic.
By providing separate reimbursement for qualifying antibiotics,
the DISARM Act would eliminate an important barrier to the use
of more expensive antibiotics.
Achaogen supports passage of the DISARM Act, and we would
like to see reimbursement for qualifying antibiotics extended
beyond Medicaid and Medicare patients to patients covered by
private insurance.
Second, the FDA needs authorization for greater flexibility
for approval of antibiotics based on limited clinical data
sets, and we have heard the rationale for that today.
Plazomicin is following a streamlined development program
with a single phase 3 trial. However, due to the need to power
the study to demonstrate statistical significance for a
mortality end point and the relative rarity of these infection
times, the enrollment period for this study is expected to take
3 years.
In contrast in Europe, recent EMA guidance extends more
flexibility in the scenario of unmet clinical need and does not
require inferential statistical testing for antibiotic
approvals.
In order for new drugs to be available ahead of the
emergence of unacceptably large numbers of drug resistant
infections, Congress must enact legislation that authorizes the
FDA to approve new antibiotics for limited patient populations
based on smaller clinical trial data sets, but where the
totality of the available evidence supports a favorable benefit
risk profile for the antibiotic while acknowledging and
reflecting the greater uncertainty associated with limited
testing in the product label.
Achaogen supports passage of the ADAPT Act to provide the
FDA with the increased flexibility that we believe it needs.
Third, there is a need for more rapid point of care
diagnostic tests and a more streamlined approval path for
diagnostics. For serious infections, a delay in the
administration of the right antibiotic by just one hour
significantly increases patient mortality. Traditional
diagnostic tests, as we have heard, from the days of Louis
Pasteur may take 72 hours to complete, and we believe the
Federal Government could make a significant impact by providing
support and incentives for the development of rapid and cost
effective point of care diagnostics that advance antibiotics
stewardship and clinical care.
There is also an opportunity to streamline the regulatory
process for development and approval of companion diagnostics
tests. There is a need for an expedited and iterative approach
to diagnostic development and approval through regulations that
are anchored in consideration of the urgency of the unmet
medical need and the overall benefit/risk for patients.
The regulation should provide the FDA with flexibility to
streamline the required analytical studies as well as a testing
related to quality manufacturing software and documentation for
the diagnostic device.
And, fourth and finally, we need sustained funding for
antibiotic research and development. We must be prepared to
take a long-term perspective in order to fully realize the
public health benefits that will be derived from increasing
funding for antibiotic research and development.
The funding that Achaogen has received from BARDA, NIAID,
and the Department of Defense have been essential, and we
believe it illustrates how public/private partnerships can
successfully advance antibacterial research and development.
We support increased funding on an ongoing and predictable
basis for BARDA's broad spectrum antibacterial program and the
expansion of BARDA's mission to allow investment and programs
designed to address the public health threat posed by
antibacterial resistance.
We also support continued funding through NIH devoted to
antibacterial discovery and development.
We appreciate the opportunity to contribute to the
discussion today, and strongly encourage Congress to take
additional measures to mitigate the very significant public
health threat posed by multi-drug resistant gram-negative
bacteria.
Mr. Pitts. Chair thanks the gentleman.
[The prepared statement of Dr. Hillan follows:]
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Mr. Pitts. And now recognizes Dr. Murray 5 minutes for an
opening statement.
STATEMENT OF DR. BARBARA MURRAY
Dr. Murray. Thank you very much, Mr. Chairman.
Thank you for inviting me to testify on behalf the
Infectious Diseases Society of America, IDSA, on the public
health crisis of antibiotic resistance and the urgent need for
new antibiotics in diagnostics.
IDSA is grateful for this subcommittee's continued
leadership on these critical issues.
Physicians are seeing more and more patients with very
serious infections that are resistant to all or almost all
antibiotics. For example, I recently saw a young woman with
severe lupus, an autoimmune disease, who developed a very
painful bile duct infection that persisted despite multiple
antibiotics, endoscopies and surgical interventions. The
infecting bacterium invaded her blood stream and it developed
resistance to every antibiotic available, including colistin, a
toxic antibiotic usually of last resort. Finally, all we could
do was send her to hospice for palliative comfort care while
she waited for the infection to claim her life after a very
prolonged and expensive stay in the hospital.
A colleague of mine recently took care of a very active
patient in his sixties following a prosthetic knee replacement,
he developed a serious pseudomonas infection that, despite
removal of the implanted joint and multiple antibiotics, could
not be controlled and he had to have an above-the-knee
amputation.
This summer I cared for two diabetic women with urinary
tract infections, or UTI, who had to be admitted to the
hospital, not because they were so seriously ill, but for IV
therapy because their infecting organism was resistant to all
oral antibiotics.
For anyone who has had a UTI, which is going to be most of
the women in this room and some of the men, having to be
hospitalized for such a common infection is inconvenient,
decreases productivity, and markedly increases our health care
costs.
Antibiotic R&D, as you have heard, faces significant
barriers. Discovery is hard. Scientific challenges lead to very
high development costs. Economically, antibiotics have a very
poor return on investment because they are typically priced
low, used for a short duration, and held in reserve by us to
try to control antibiotic resistance.
IDSA thanks the subcommittee, and especially
Representatives Gingrey and Green, for its leadership in
enacting the GAIN Act in 2012, which is beginning to address
some of the economic barriers. We hope you can now build on
these efforts and address current regulatory barriers.
Specifically, extensively resistant bacteria currently
infect relatively small numbers of patients, making it
virtually impossible, as you have heard, to populate
traditional, i.e., large clinical trials, but we need to
develop new drugs before there is an epidemic. Think of how our
fear for Ebola would be much less if there were already
effective therapies.
Representatives Gingrey and Green introduced the ADAPT Act,
which would address this regulatory conundrum by allowing FDA
to approve certain antibiotics with smaller trials. This
approach would only be for antibiotics to treat serious
infections where there is an unmet medical need. ADAPT would
make trials of highly resistant bacteria feasible, possibly
less costly, and it would allow FDA to assess the risk of a new
antibiotic relative to its potential benefit to this limited
population.
IDSA is deeply concerned that without ADAPT many of the
most urgently needed antibiotics would not be brought to the
market. The strategy of a limited population approval pathway
was also suggested in the PCAST report that you heard
yesterday.
ADAPT includes safeguards to help ensure that these drugs
are used appropriately. It also contains multiple important
provisions to ensure that susceptibility tests, interpretive
criteria, or break points, which predict whether a patient will
have a good response to an antibiotic, are quickly updated and
made publicly available.
Up-to-date information is crucial for clinical care and to
ensure that antibiotics are not misused or overused.
IDSA urges the subcommittee to mark up the ADAPT Act
swiftly.
As also mentioned in the PCAST and earlier today,
additional economic incentives are required, such as public/
private partnerships; support for Federal agencies that invest
in antibiotic researched; improved reimbursements and/or tax
credits.
Ernst & Young estimated that an IDSA tax proposal targeting
R&D for these needed antibiotics would result in an additional
five to seven new antibiotics in the pipeline every year.
While new antibiotics are critical, IDSA is also committed
to a multi-prong response to antibiotic resistance, including a
well-coordinated Federal leadership, as mentioned in the PCAST
report; sustained involvement of nongovernment stakeholders;
antibiotic stewardship programs in every health care facility;
enhanced surveillance of antibiotic use and resistance
patterns; and research on novel strategies to prevent and
control antibiotic-resistance organisms. These steps are
critical to protect patients, the public health, and the
Federal investment in new antibiotics.
Lastly, again, as you have heard, it is extremely important
to promote the development and clinical integration of new
diagnostics. Rapid point-of-care diagnostics can reduce
inappropriate antibiotic use which drives resistance by
lessening the need for empiric or shotgun therapy.
IDSA recommends increased investments in diagnostics
research, regulatory approval pathways, strengthening in
reimbursement, and supporting outcomes research to demonstrate
the impact of diagnostics on patient care.
Thank you again for allowing me to testify here and for
your continuing efforts in this very important area.
Mr. Pitts. Chair thanks the gentlelady.
[The prepared statement of Dr. Murray follows:]
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Mr. Pitts. Now recognizes Dr. Thomas. Five minutes for
questions.
STATEMENT OF DR. ADRIAN THOMAS
Dr. Thomas. Thank you, Chairman Pitts and members of this
committee for this opportunity to come before you today.
I am Dr. Adrian Thomas, vice president at Global Market
Access and head of the Global Health function at Janssen which
is the pharmaceutical business of Johnson & Johnson.
On behalf of Johnson & Johnson, I applaud you for
organizing this hearing and commend all the leaders in this
room for giving voice to the dire situation of antibiotic
resistance.
We also recognize this committee's and Congress'
leadership, as well as the leadership of President Obama on
this important issue, and we offer our support for the national
strategy announced yesterday.
Today I bring the lens of a private sector physician
through more than 30 years' experience in public health from my
early career in the Australia's Flying Doctor Service to my
current role overseeing Janssen's portfolio of production and
services for diseases of high public health impact, which
include HIV, tuberculosis, and also more recently, Ebola.
I am a clinical pharmacologist and physician by training,
with additional expertise in a variety of areas in the health
care industry. The majority of my 17 years in the private
sector has been with Johnson & Johnson.
As many of you know, Johnson & Johnson is the world's
largest and most broadly based health care company, with a
portfolio that also includes diagnostics and devices as well as
the consumer products.
We are an innovation-based business, and it is critical, as
you think about this issue, that we address incentives that
apply and are relevant to many different stakeholders in the
area of innovation, not just large companies, but discovery,
academic research, biotechs and start-up in the public sector.
Our place in and reach across the health care innovation
ecosystem allows us unique visibility into both the number and
the status of projects underway across areas of unmet need,
including antibiotics. It also leads me to comment that as we
consider incentives for antimicrobial resistance, we should
also consider incentives in vaccines and other preventive
mechanisms and diagnostics if we are truly going to make
progress against this terrible issue.
Our work also brings us into proximity with patients facing
life-threatening illnesses, including patients with these
infectious diseases. Their stories affirm what we have heard
day; that we must do more to meet their needs.
First and foremost, we must work together and think
differently to bring forward new therapies. We have heard in
some detail today that despite the need in recent efforts to
improve it, including legislative efforts, the innovation
climate for antibiotics and other antimicrobial R&D remain
suboptimal. That is, in large part, because the basic science
with this field continues to be very difficult with high rates
of failure. If failure is no longer an option given this
critical and growing global health security, I would term it,
crisis, then we need to take different measures.
We can learn lessons and warnings from the Ebola crisis,
which was also neglected, and which now we have companies
scrambling, including our own, to try and provide new vaccines
within unfeasibly short time frames and unfunded mechanisms.
While strategies for better stewardship of antibiotics on
the market are vital in the fight against resistance, current
conditions demand that we need a new framework for innovation
in antibiotics R&D. We have to track the world's best and
brightest to this challenge, including the private sector.
As is done in other areas, the U.S. can and should lead the
world in creating enabling conditions. We cannot wait for the
European's Medicines Initiative to solve the problems for us.
It is our hope that this committee and the Congress will
give serious consideration to new legislative proposals. Beyond
this, we believe there remains the need to put forward a
comprehensive set of both push and pull incentive options
specific to antibiotics that address the need for R&D across a
wide range of stakeholders.
We must create a broad set of highly attractive although
financially manageable incentives to engage the many different
biomedical innovator companies large and small in this work,
including academic networks.
The policies can and should be able to take into
consideration a holistic view of the costs and risks of this,
and also the costs and risks of developing, introducing, and
supporting these products worldwide. And how those risks are
different for different stakeholders and the incentives must
address, therefore, those different stakeholder perspectives.
I would like to talk a little bit about transferable market
exclusivity. We have heard different perspectives on this
topic. As our company has undertaken its own in-depth analysis
of different incentive proposals for antibiotic R&D, it is
apparent that many existing proposals only offer marginal
valuations.
In addition to being a physician, I serve on the investment
committee of our pharmaceutical business. I balance the
difficult choices we have to make about, is Ebola, is multi-
drug resistant tuberculosis, is diabetes, is cancer a more
important public health question, and is it also financially
feasible for us to balance our research efforts in this area.
Spending almost $5 billion annually in research in
pharmaceuticals, these decisions are not easy, and often have
timeframes of 10 to 15 years.
Thinking about transferable market exclusivity, the notion
of an exclusivity that can be applied towards another product
not only gives certainty the investments be made in very high-
risk areas, but also disincentivize activities that might
otherwise undermine both the public health stewardship and the
protection of these products and assets need to offer against
emerging and developing antibiotic resistance to encouraging
appropriate use.
The bottom line to our proposal is we believe we have to
have more shots on goal, more basic research, more discovery,
more biotech start-ups, more academic partnerships, more
companies investing, and the in-house facilities to recognize
and take up new assets, and to conduct the expensive research
necessary to deliver and develop these products to the
marketplace.
In conclusion, we welcome the changes in public policy to
stimulate new antibiotic R&D, and thank you very much for your
time today.
Mr. Pitts. Chair thanks the gentleman.
[The prepared statement of Dr. Thomas follows:]
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Mr. Pitts. And now recognizes Mr. Outterson. Five minutes
for an opening statement.
STATEMENT OF KEVIN OUTTERSON
Mr. Outterson. Good morning, Mr. Chairman, and thank you,
for inviting me to testify today.
I am a professor at Boston University. I also serve on the
Centers for Disease Control and Prevention Antimicrobial
Resistance Working Group, and at the Royal Institute for
International Affairs in London as a visiting fellow at Chatham
House.
My remarks today are my own, but at Chatham House, the work
that we have been doing for the past year is focussed onto
linkage.
I think today we need to focus and act decisively because
the business model for antibiotics is broken. Not only for
antibiotics but for other things that treat and prevent
infectious diseases such as diagnostics, vaccines, infection
controls, and related devices.
And so I have a couple of slides here to look at the
business model, and the slides are based on the study that was
done by the Eastern Research Group of which I was a part, I am
a co-author of that study, for the department of Health and
Human Services.
This first slide no one in the committee needs to see this,
honestly. We know that this a huge problem. The actual number
of deaths in the CDC threat assessment was 37,000 per year
because they included Clostridium difficile. It is a huge
problem.
So let's look at the business model, and we are looking at
the net present value from a private perspective. This is a
company looking to make a decision about whether to invest in a
molecule at an early stage. And this is a typical decision tree
which tries to analyze for the company what is the chance of
failure at each stage and how much it will cost to advance the
molecule through.
Every company uses a model like this. Everyone might use
slightly different assumptions or numbers in it, but this is a
typical thing done in the industry. In fact, there is in
England right now at the Office of Health Economics using
AstraZeneca data there is another study almost completed which
comes out with I must, sad to say, much gloomier numbers than
what we present here today.
So the business model is broken. The first thing we looked
at, the FDA and Health and Human Services asked us to look at
six bacterial indications, and it is hard to read, and I am
sorry for that, but what you need to see is that the companies
were hoping for $100 million net present value. That was the
money that they would get in return.
And you see here on the arrow bars and on the colored
things that for several of these indications they have a
negative net present value. They are actually going to lose
money after they build a factory to make this drug. And for
others there was a positive one but nowhere here the $100
million threshold that was necessary for companies to move
forward.
The red arrow bars, the little light thing, is the 90
percent confidence interval. For every single indication, the
confidence interval included a negative number. So it is really
difficult for companies to commit to research programs in that
sort of space.
The second thing we were asked to look the is the social
net present value. How valuable are these drugs to society.
Now, we didn't have speculative numbers here. We didn't look at
the effect on reducing resistance. We didn't model how it would
keep us all working. You know, the kind of ancillary effects.
We just looked at the direct cost for society. And yet the
numbers we came up with were huge. These numbers are in the
billions, and the arrow bar ranges are huge. So the social net
present value for many of these drugs was two orders of
magnitude higher. Several billion dollars for several of these
drugs.
In other words, society would be getting a tremendous
bargain if it was able to procure one of these drugs for even a
fraction of that amount.
As a comparison, I compared for each of the six indications
the social and the private, and if you look real carefully, you
can't even see the private on the same scale because it is in
blue. It is so small it is almost impossible to see. There is a
huge gap here.
So I did just one and tried to stretch it out across the
slide, and you can barely see the blue for HABP/VABP. OK? And
so what I did here is I truncated everything at 100 million.
Those red bars really would go up another 15 feet on the wall
if I allowed them, and that is the gap between the social and
private value. It is another way of saying we are tremendously
under reimbursing for antibiotics.
We also looked a incentives, and given that I have 30
seconds, I will get down to the key chart in which we modeled
which incentives could we change in order to solve this $100
million benchmark. We looked at every incentive ever published,
I promise you, and then put them in the different categories
and fed them into some model.
The short answer is that if you do something that affects
the cost of capital, it has to be fairly significant in order
for it to work. So if we had tax credits or BARDA funding, it
better be significant in order to kick in; something on the
range of a billion dollars per molecule we would want coming
out the other side. So we are not talking small change. It is
large.
Yesterday's proposal from the president $800 million under
BARDA, they are hoping for one drug per year out of that. I
think it is a reasonable number.
Things that don't seem to work based on the model. We even
had unlimited perpetual forever patents. It still didn't get
the companies anywhere near the $100 million threshold.
Similarly, to reduce clinical trial times, you would have
to reduce it by 75 percent. So ADAPT could be very useful to
bring a new drug to market for the people who need it today,
but it should not be viewed as a powerful economic incentive
for a company early in the stages to decide now is the moment
to green light this drug. It doesn't have that sort of effect.
What the companies need is money, not the promises of earlier
approval.
Thank you.
Mr. Pitts. The chair thanks the gentleman.
[The prepared statement of Mr. Outterson follows:]
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Mr. Pitts. Now recognizes Mr. Coukell 5 minutes for open
statement.
STATEMENT OF ALLAN COUKELL
Mr. Coukell. Mr. Chairman, I would like to thank you and
the ranking member and the members of the committee for the
opportunity to be here today.
My name is Allan Coukell. I direct drug, medical device,
and food programs at the Pew Charitable Trusts. We are
independent research and policy organization with a
longstanding focus on the urgent need for new antibiotics.
As you have already heard, the dwindling pipeline of
antibiotics is a potential public health crisis. Every one of
us will need one of these drugs in our lifetime, and most of us
already probably know somebody who has had a resistant
infection.
Children and seniors are particularly vulnerable, as are
members of the military. One-third of those injured in Iraq and
Afghanistan came back with an infection, some of them resistant
to almost all existing drugs, and among the broader population,
23,000 Americans die every year from resistant infection.
So a comprehensive response requires infection prevention
and surveillance in reducing unnecessary use and better
diagnostics. But my focus today is steps to reinvigorate the
drug pipeline.
And the state of the pipeline is not good. A Pew analysis
included in my written statement finds 38 drugs, antibiotics,
now in clinical testing. Five of them in advanced development
have some potential to treat Gram-negatives, which are probably
the most serious immediate threats. That may sound encouraging,
but let's recognize just based on general trends that 80
percent of those won't reach market. They will fail because of
reasons of toxicity or lack of effectiveness.
What is more, very few of the drugs now in development
actually have novel mechanisms of action that would
significantly delay the onset of resistance.
So what can be done? By passing the GAIN Act two years ago,
this committee has already taken a leadership role. GAIN,
introduced by Dr. Gingrey, Mrs. DeGette, and Mr. Green extends
market exclusivity for certain antibiotics. This gives
companies a better chance of a positive return in investment.
GAIN also ensures swift FDA review of these drugs.
That was an important first step, and more is needed,
especially for the infections that are hardest to treat, and as
has been mentioned, trials of antibiotics are hard because only
a small proportion of the population with, say, pneumonia has a
resistant bug at any given time.
So to help address these challenges, Dr. Gingrey and Mr.
Green and a long list of bipartisan cosponsors have introduced
the ADAPT Act. ADAPT would create a new FDA approval pathway
for antibiotics to treat patients with few or no other
treatment options. This approach, which is also called LPAD,
for Limited Population Antibacterial Drug, meets both a public
health goal and helps streamline development.
So let me make it concrete with two different scenarios.
Imagine drug A which is approved for a range of bacterial
pneumonias, some easily treated, some resistant. When FDA
approves drug A, it has to consider the universe of people who
might get it. Some of them have lots of treatment options and
won't be willing to accept greater uncertainty.
Now take a second drug, drug B, which is an LPAD drug only
for life-threatening pneumonias caused by a resistant organism.
The patient with this infection may well die if he doesn't take
drug B. So the potential benefit may be greater against the
uncertainty.
And the FDA, in making a benefit/risk calculation only for
patients like our patient, can accept less data in approving
the drug. That reduces development costs.
To be clear, this does not change the standard of approval.
It merely targets a specific population that is different from
the general population.
For LPAD to work as intended, health care providers have to
know and understand that the drug is approved for the limited
population based on limited data. The drug's special status has
to be clearly communicated through drug labeling and any
marketing materials.
To vet this concept, Pew has worked with the Infectious
Disease Society, antibiotic stewardship personnel, drug
companies, health insurers, the FDA, and others, and this
legislation has the support of numerous and diverse
stakeholders, and yesterday PCAST, the President's Council of
Advisors on Science and Technology, also called for such
legislation.
This committee has long understood the threat of antibiotic
resistance and has done much to bring it to the national stage,
and we appreciate your leadership and continued commitment.
Let me conclude with the observation that we face many
intractable problems in many diseases that seem intractable.
This is not one of them. Bacterial infection is a solvable
problem. Penicillin and the heyday of the drugs that followed
effectively conquered bacterial illness for a time, and we can
get back there if we commit and ensure that we do it again.
I thank you and I welcome your questions.
Mr. Pitts. The Chair thanks the gentleman.
[The prepared statement of Mr. Coukell follows:]
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Mr. Pitts. Now recognizes Dr. Powers 5 minutes for an
opening statement.
STATEMENT OF DR. JOHN H. POWERS
Dr. Powers. Thank you very much, Mr. Chairman. Thank you
for inviting me to testify.
I am a practicing infectious diseases and internal medicine
physician, and a medical researcher who actively cares for
patients. I was a scientist at FDA for almost a decade and the
co-chair of the Inter-agency Task Force on Antimicrobial
Resistance, and I am a member of the WHO Advisory Group on
Antimicrobial Resistance.
I am speaking today on behalf of the National Physicians
Alliance. NPA is a professional home to physicians in more than
40 medical specialties. We share a commitment to patient-
centered health care, evidence-based health policy, and
professional integrity. NPA does not accept pharmaceutical
company funding. We believe in the advancement of knowledge
through research that is free of financial conflicts of
interest, transparent, and peer reviewed. NPA's FDA Task Force
was established to support our work in defense of a strong
scientifically rigorous FDA.
As members of this committee have pointed out, studies of
infectious diseases in the early 1900s, at a time when there
were no effective therapies, were the first to use the modern
methods of adequate and well-controlled trials that are a part
of law today. Investigators and then members of Congress
realized that appropriate study methods are critical in order
to separate the harmful from the helpful for patients.
The problems of antibiotic resistance and the scientific
and regulatory responses to it are also not new. Dr. Scott
Podolsky in his recent book, The Antibiotic Era, recounts that
during the rise of resistance the common staphylococcal
infections in the 1950s, drug companies marketed numerous
ineffective antibiotics based on supposed superiority in the
test tube.
Dr. Maxwell Finland, the first president of the Infectious
Diseases Society of America, with 19 other prominent infectious
disease clinicians, pointed out the need for adequate and well-
controlled studies in patients. He said, ``Properly conducted
clinical studies may support the claims and justify the
enthusiasm for these antimicrobial agents, but it is incumbent
upon those of us who are intimately concerned with the welfare
of our patients to wait until such data are presented before we
accept and acclaim any new agents or recommend them for general
use.''
In 1962, Dr. Finland made these same points at the Senate
hearings that resulted in adding the requirement for
effectiveness for new drugs based on substantial evidence from
adequate and well-controlled studies showing that, like with
other drugs, antibiotic effectiveness cannot be assumed based
on test tube tests, animal studies, or mathematical modeling,
but can only be verified by studies that ask the right
questions with the right outcomes in the patient who might
benefit from experimental drugs.
The problem of antibiotic resistance today is the same as
it was in years past. The unmet medical need exists in those
patients who have no effective therapies. The need for
treatments with improved effectiveness compared to older
treatments on the outcomes of decreasing death or irreversible
disability, not alternative outcomes. The program described by
Dr. Hillan exactly focuses on this population and these
outcomes.
Drugs marketed as life saving should actually be shown to
save lives in adequate and well-controlled studies using
appropriate diagnostics such as those we have discussed this
morning and advocated in yesterday's PCAST report to select the
patients who would receive added benefit from those drugs. And
susceptibility criteria should be based on patient outcomes,
not mathematical modeling from sources without conflicts of
interest.
Drugs that are highly effective need few patients to show
those effects in adequate and well-controlled studies.
Therefore, the sample size of a study is related to how
effective the drug actually is.
It is ethically questionable to expose our patients who
have any current effective and safe options to less effective
treatments in order to have a robust pipeline or as an economic
stimulus to companies. It is scientifically invalid to test
drugs in patients with disease due to susceptible organisms and
then assume effectiveness in older sicker patients with disease
due to resistant pathogens based on assumptions from modeling
and individual and anecdotes.
Recent clinical trials of new antibiotics carry warnings on
FDA Web site of increased death compared to older effective
drugs despite promising test tube tests, animal models, and
mathematical modeling. A recent study by AHRQ showed a lack of
evidence that this kind of mathematical modeling has been shown
to result in better patient outcomes. This shows that now, as
in past years, preliminary information is not a substitute for
clinical studies in patients.
Patients who wish to take an informed risk should have
access to these drugs through requirements for expanded access
under existing FDA programs for patients who do not qualify for
ongoing clinical research studies, as was done in the early
years of the HIV epidemic to allow access to new therapies
while the drugs are continued to be evaluated in adequate and
well-controlled studies prior to widespread marketing.
FDA labeling should accurately reflect the benefits, the
types of patients who benefit, how clinicians should select
those patients, and the information used as the basis for
approval. Telling clinicians a drug has not been studied
properly does not help clinicians prescribe new drugs
appropriately.
Our written testimony provides NPA's plan for a
comprehensive approach to development, disease prevention,
stewardship, diagnosis and reimbursement strategies for
improved therapies of infectious diseases in line with the
recommendations from the president's PCAST report released
yesterday.
Dr. Finland sums up the issues we discuss today and that we
as physicians still agree with today when he said, ``Clinical
investigators and authors of medical and scientific
publications have the duty to protect the medical profession
and the public against the abuse of preliminary scientific
information and against the improper and premature exploitation
of conclusions based on inadequate data.''
Thank you very much for the opportunity to testify.
[The prepared statement of Dr. Powers follows:]
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Mr. Pitts. The chair thanks the gentleman, thanks to all of
the presenters for their testimony. We will begin questioning,
and I will recognize myself 5 minutes for that purpose.
Dr. Thomas, you mentioned in your testimony that a multi-
pronged strategy is needed that includes both stewardship and
antibiotic innovation incentives. If you think about the path
to cures as being three phases, discovery, development, and
delivery, do you believe that we need incentives in all three
phases to have an effective incentive strategy?
Dr. Thomas. Thank you for the question, Mr. Chairman. Yes,
I do, because I think often the players or the stakeholders who
are conducting that research at those different stages are
different. And what incentivizes academic or biotech startup
might be different from what incentivizes a multi-national
corporation like Johnson & Johnson, might be different from
organizations that are involved in healthcare delivery.
So one incentive is not going to--as we have seen, frankly,
since we have had incentives introduced, we still have an empty
pipeline of incentive is not going to solve this problem. It
may well be that large grants or so-called prizes would attract
academic researchers and startups. A very different incentive
needs to encourage venture capitalism to go and back startup
companies with a much higher level of risk. And for a company
like Johnson & Johnson, we look at a portfolio of investment
opportunities, need to understand which of those is both most
important medically and to human impact but also which is most
viably able to be conducted, and finally, which enables us to
balance our risk and our return.
Mr. Pitts. All right. Let's look at each phase. First of
all, what types of discovery or R&D incentives do you believe
would encourage companies to develop new and novel antibiotics?
Dr. Thomas. I think we need to look at the discovery
incentives not just for antibiotics, but also for antibiotics
in adjacent technologies. Here it is absolutely critical that
we focus on point of care diagnostics, biomarkers, new
capabilities of being able to diagnose, and also to advance
clinical research in this field. For this sort of endeavor,
this is where large grants, funding, prizes would make the most
sense, tax credits, because they will encourage broad-based
academic research as well as broad-based technology company
research that is often shorter in duration and is able to be
managed in a different way.
As we think about the incentives for development,
development in the pharmaceutical process is the most expensive
piece. We recently brought a new product called SIRTURO, which
is indicated for multi-drug resistant tuberculosis. With 13
years of R&D and early development, we had proof of concept
that was compelling, and through the leadership of agencies
like the FDA and the European Medicines Agency and the World
Health Organization had a conditional approval on early phase 2
results.
We still have more than 15 years of clinical trials
evidence generation showing safety and effectiveness in
children, showing safety and effectiveness versus other drugs
in real-world use in the field and proving out the hope that we
saw in the phase 2 studies. Having spent well over $200 million
to date with no commercial return foreseeable for this product,
and nor necessarily should there be, we are now looking at a
further 15 years of investment and many hundreds of millions
more.
Tax credits are not enough to spur that sort of effort on a
broad base across the industry. And I think for drug
developers, we need to make sure that there is a very definite
incentive for 2 things: One is, how can they justify
maintaining the infrastructure in-house, the competency to
understand what is a good asset and how to develop it, whether
or not they have one of those assets themselves, and that is
critical because lightning doesn't always strike in New
Brunswick where our headquarters is. Lightening for innovation
strikes all over the world, and we have to be able to
understand when it hits, what that technology is worth.
The second thing is we have to be able to encourage
companies to actually invest in the long-range risks associated
with the large dollars for drug development, and the way to do
this is not to hope that they have a certain expertise in one
drug. The way to do this is to say we want as many shots on
goal as possible by as many large players as possible so that
we can see a sustainable and continual pipeline to evolve, and
for this activity, this is where the concept of tradeable
vouchers or exclusivity additions comes in because what you are
not doing is incentivizing people to go down a loss-making
path. You are saying we understand that you have to go down a
profit-making path in some of your business and we will trade
off against these activities.
Finally in the area of the delivery side, this is really
problematic. By the nature of the sort of research we conduct
to get products approved for antimicrobial resistance, we are
looking at non-inferiority studies. From a payment perspective,
that usually means in most countries in the world that you get
price parity. Despite the fact that your price parity with what
is on the market was for costs that were achieved many, many
years ago and may not no longer be relevant, and that is why
the ENPVs you heard about before are usually negative, so the
notion of a price premium or reimbursement incentives are
certainly attractive in that area.
I would posit, however, and use as an example our own
experience in multi-drug resistant tuberculosis, when you are
talking about highly resistant bugs, highly transmissible bugs,
you want the drugs used only in the people who need them, only
for the bugs that need them, and by people who understand how
to treat and use those products in an appropriate way. That is
not really a very strong economic model for understanding how
your product, even with a reimbursement incentive, is actually
going to be successful. In fact, it is probably a negative
commercial model in most areas.
Mr. Pitts. The chair thanks the gentleman. Now recognize
the ranking member of the full committee, Mr. Waxman 5 minutes
for questions.
Mr. Waxman. Thank you, Mr. Chairman. Last Congress we
passed the GAIN Act to provide new incentives for the
development of important antibiotics, and under that Act,
antimicrobials and antifungals intended to treat serious or
life-threatening infections can be designated as qualified
infectious disease products, or QIDPs. We receive a priority
review, that is helpful. If they are approved, they get an
additional 5 years of protection from generic competition. That
is a strong incentive. FDA has already granted QIDP
designations to almost three dozen different antibiotics, so
companies clearly are interested in this program.
A major impetus for the GAIN Act and for today's hearing is
a need for new antibiotics to treat the growing number of life-
threatening pathogens that are resistant to all or virtually
all antibiotics. However, in your testimony, Mr. Outterson, you
note that there is nothing in the law that requires QIDP
designations be only given to antibiotics intended to treat
resistant pathogens. As a result, you assert that essentially
every antibiotic ever approved by the FDA would qualify as a
QIDP.
Some of us, during the FDA Safety and Innovation Act
negotiations tried to limit it, that designation to those
antibiotics that would fulfill an unmet medical need. However,
we were unsuccessful.
Can you tell us how many, or what percentage of the QIDPs
are for antimicrobials intended to treat highly resistant
pathogens, and are their public health impacts we should be
concerned about as a result of the lost failure to prioritize
drugs for resistant pathogens, and how could we better
incentivize the development of the drugs we most need?
Mr. Outterson. Thank you for your question. The definition
of Qualified Infectious Disease Product is built on a previous
definition of a qualified pathogen. And that list does not
require any of the pathogens to be resistant. It includes most
species known to cause any disease in humans. So, because it is
difficult sometimes in these trials to run them where it
historically hasn't been done, to run them on people only with
resistant pathogens. So you are correct in saying that the
qualified infectious disease product will apply probably to
every antibiotic that will be approved in this next decade or
two, which is a question about whether the incentives are
properly targeted.
On the incentives themselves, when I talk to companies
privately, large companies as well as small, they all say that
the incentives in GAIN were in the correct direction, but there
is a quiet walk when what we should be doing is running, that
the economic value to them, of these incentives is really very
small. They will take them and register, but it is 1 percent of
the way to where we need to go to change the economic model. It
is a small change, and we should be doing something else.
Mr. Waxman. So tell us how to change this economic model.
You talked about that in your presentation. How much do we have
to keep giving in order to give the right incentives? And we
ought to know how much this is going to cost the American
people and whether it going to be successful.
Mr. Outterson. To use the three stages that the chairman
mentioned. On the discover side, our NIH budgets need to be
dramatically increased. We need basic science.
Mr. Waxman. Yes.
Mr. Outterson. It was the PCAST report yesterday.
Mr. Waxman. And we have been cutting back on that.
Mr. Outterson. It has been flatlined or slightly negative
for the past half decade to the best of my knowledge on
antibacterial research in the NIH. The second piece on
developing, I think tax credits are a piece of that. I think
BARDA is a huge piece of that. Some of the best gram negative
molecules in development now have a lot of money in them from
BARDA.
Mr. Waxman. We have given tax credits. We want to shorten
the time at FDA to get this review done as quickly as possible
to get the drug out there. We want to help companies decide its
in their economic interest to do this. What do we need to do?
Mr. Outterson. The last piece is when it is delivered to
the public, and I would agree with Dr. Thomas that there is a
reimbursement problem, but I don't particularly like the
solution. At the Chatham House work, we are looking at the
linkage, which is just saying the companies will be generously
rewarded but on something that has nothing to do with volume.
I think everyone here would agree we don't want to put
$100,000 price on a drug and give a company a reason to over-
promote it. And so there needs to be significant price-type or
BARDA grant-type rewards for companies, possibly based on an
insurance model, which is what GlaxoSmithKline has suggested,
to give significant rewards to the companies after they have
delivered a drug to the market.
Mr. Waxman. Well, I would suggest that we may be better off
putting much more money into biomedical research at NIH and
throughout universities around the country because they don't
have the profit motive and what they do helps the companies
because that science is then used for these products.
But if the companies are having too difficult a time
without enough incentives to make a lot of money, well, let's
make sure that we get the work being done at the public expense
because otherwise, we are going to pay a lot of money and we
may not see the results that we need. You agree?
Mr. Outterson. I completely agree. If we do not have enough
basic science, the pipeline that flows to venture capital and
then to the larger companies runs dry.
Mr. Waxman. Thank you. Thank you, Mr. Chairman.
Mr. Pitts. The chair thanks the gentleman. Now recognizes
the gentleman from Georgia, Dr. Gingrey, 5 minutes for
questions.
Mr. Gingrey. That was a very interesting line of
questioning from the distinguished ranking member of the
committee, and Mr. Outterson, your response was not unexpected.
But there is something to say for the profit motive as well.
You give more and more and more money, taxpayer money to NIH or
wherever basic research is being done, and you don't have this
profit motive that you are talking about and the wrong
incentive, misguided incentive, but if you don't have somebody
with the profit motive, a company, a pharmaceutical company,
big or small, you can sit there doing basic research for 100
years, and maybe some brilliant scientist, many of them could
be very comfortable in their labs and enjoy that to a fare thee
well. I think I would. But you never really get to where you
need to be in regard to drugs that treat patients that cure
these terrible bugs that are killing them.
So I am going to shift my question to Dr. Murray as
President of the American Society of Infectious Diseases to
basically ask you the same question, Dr. Murray. The business
model for antibiotics, diagnostics, and vaccines is broken. I
think we will all sort of agree with that. That is what we have
learned this morning in this rather long two-panel hearing, but
it has been good, but it a broken model. What specific steps,
Dr. Murray, do you think Congress should take to address this
crisis? Do you agree with Mr. Outterson? Do you agree with Mr.
Waxman? What do you think?
Dr. Murray. Well, I could take Dr. Woodcock's approach and
say I am not an economist, but I will try to address it. I
think basic research input is an important component. I am
biased. I do basic research in my laboratory, but I agree also
there has to be a reward at the end, and the suggestions I have
heard from others, and they are not my own, include taking
certain drugs out of the DRG so that they are not part of the
total hospital budget, which means everybody is trying to
attack on antibiotics as one place to decrease cost.
That or the other model is buying up a number of doses at
the end of a product, so they are bought up. I think perhaps
that is what you meant by the insurance model. So you hope you
never have to use them. They would be there but it guarantees
the industry some return on their dollar. So those are the
two--in addition to, of course, in the development phase, the
tax credits, but the end product, I have heard it for many
years, there has to be--they answer to taxpayers. I mean, I am
sorry, they answer to stockholders. They don't answer to
taxpayers, and so the companies cannot just be motivated by the
greater good.
Mr. Gingrey. It is kind of like when we talk on this
committee about energy and the energy policy that we should
have, and all of the above policy is the one that I like the
best, and I think really in regard to this, too, because I
mean, as Mr. Waxman said, you are talking about tax credits,
you are talking about what you just said, Dr. Murray, of buying
back a certain volume that is not used because you don't want
to just incentivize based on sales, and more grants to the NIH.
All of the above, really. I think that is the way we ought to
look at it.
I have got a little less than a minute left, and I want to
shift to Dr. Hillan. You mention in your testimony that half of
the investment cost necessary to support your drug, SIRTURO; is
that correct?
Dr. Hillan. Plazomicin.
Mr. Gingrey. Yes.
Dr. Hillan. Plazomicin.
Mr. Gingrey. Will be required. Half of the investment cost
necessary to support it, that drug, will be required after the
point of the United States regulatory approval. What drives the
cost of these investments post-FDA approval? What is the big
cost driver?
Dr. Hillan. Sure. So I'm not sure if it was me, but I am
certainly happy to answer that. There is an ongoing process
after a drug is approved so that you actually understand the
safety and effectiveness of the use of the product in the real
world. There are additional pediatric studies which are very
important. How do you--we believe our drug will be dosed in
small----
Mr. Gingrey. Well, let me shift. Just I have got no time
left, but Mr. Chairman, if you will bear with me because I
really--and thank you, Dr. Hillan, and I really want to address
this question to Dr. Thomas, so if you could quickly respond.
Mr. Chairman, if you will bear with me.
Dr. Thomas. Sure. And thank you for the question. Getting
regulatory approval is really the start of a long process of
paying for regulatory approval all over the world in a
sequential basis for maybe over 100 countries. There is
completion of commitments and unknown questions about safety.
There is, as I said, 15 years of pediatric research, so with
antibiotics that sometimes have toxicity starting at a 15-year-
old and proving that, then a 10, a 12 and a 2 and so on. There
is drug safety reporting requirements that when you have a
commercial product, these are all costs of doing business, but
when you have a product where the aim is not to use it unless
you absolutely have to, it is just a tremendous overhead that
you can't really discount any other way. It is the right thing
to do and it is the way that we do it today, but it has caused
a significant overhead.
Mr. Gingrey. And I thank both of you for your response to
that question. Thank you very much. Mr. Chairman, I yield back.
Mr. Pitts. The chair thanks the gentleman. Now recognize
the ranking member, Mr. Pallone, 5 minutes for questions.
Mr. Waxman. Mr. Pallone, would you yield to me 1 minute?
Mr. Pallone. Yes, surely.
Mr. Waxman. I thank you for yielding. I don't think Mr.
Outterson or I thought or would want anybody to believe that we
thought you don't need a profit and you don't need the private
enterprise, and I argue we need to put much more in the
research side of it, but we do need a business model that says
to a company if you do this work, you are going to make a
profit. You have got to make a profit; otherwise, they are not
going to do it, and to make a profit, we don't want to just
sell more antibiotics. We want to make sure they get a profit
so that we want to guarantee we could take their investment,
guarantee a certain percentage, and say that is how much the
government will pay you. That is one idea.
I don't know if it is the only idea, but it is obviously a
different kind of incentive that we have in other areas. So I
thought Dr. Gingrey was right when he said all of the above. We
got to do whatever we can, and I believe a lot more in public
investment because the pharmaceutical engineers are not going
to make a lot of investment in this area when their research
investments can result in a blockbuster drug, but this is a
social need, and they have got to do what we need them to do,
but they are not going to do it without making a profit. So
thank you for giving me that chance----
Mr. Pallone. Sure.
Mr. Waxman [continuing]. To add that additional thought.
Mr. Pallone. Thank you. Thank you, Mr. Waxman. I wanted to
ask Dr. Murray and Mr. Coukell. I know that IDSA and Pew have
worked very closely with the sponsors of the ADAPT Act, and
they are strong supporters of it, I would like to get your
views on a few aspects of this legislation. First, I am
concerned that as currently drafted, FDA may not have adequate
authority to require that an ADAPT antibiotic be labeled in a
way that calls attention to the fact that it is intended only
for special populations. I don't think putting such a statement
in the prescribing information is adequate, and I am concerned
that if such drugs are used more widely than appropriate, that
we could end up both harming patients and losing the
effectiveness of the drug to antibiotic resistance.
So what are your views about the adequacy of the current
labeling language in the bill? Do you agree that it is critical
that there be a strong and prominent labeling statement to
signal to providers that they should use the drug only in
circumscribed situations? And I guess we could start with Dr.
Murray and then go to Mr. Coukell.
Dr. Murray. Well, I think it is important to have some
label there. In a practical sense, what we do in the hospital
to prevent overuse of certain drugs, is we already have
stewardship in place in our county hospital, certain
antibiotics, be they for cost, toxicity, or whatever reason,
have to go through an infectious disease approval. That is
already in place.
Another thing we sometimes do is we don't report on the
chart of the report that goes to the patient's chart, the
susceptibility to certain antibiotics. If you are in infectious
diseases or smart enough to know what is going on, you know to
call the laboratory and ask for that susceptibility so the
doctors that are actually caring for these multi-drug resistant
infections know to do that. Usually it is done because there
are certain combinations that even though the antibiotic is
susceptible, you wouldn't use it alone.
The third way with the electronic records that might be
possible that I was thinking about last night is that when this
drug is written for, there is an automatic pop-up. We have all
sorts of automatic pop-ups now, and an automatic pop-up could
say this has been approved in a limited population. I think in
many ways--there may not be as much of a problem as people are
imagining. These infections occur in certain settings, usually
in intensive care units, they are complicated. Infectious
disease physicians are usually involved in these patients.
For someone to try to use this drug or a special drug that
has been approved in this fashion for an ordinaryE. coli
infection, there is not a need to do that. The companies are
not going to be able to be out there marketing for that
purpose. FDA will be overseeing what goes into the promotional
materials, so I am not sure the ordinary physician--certainly
the one out in the community is never going to even think about
using it. These are IV drugs by and large. So I think there is
some inherent safeguard.
Mr. Pallone. OK. Mr. Coukell, do you want to respond?
Mr. Coukell. Thank you for that question, and let me build
on what Dr. Murray has said that we have worked very closely on
this bill, and we think this is the one place that we really
would like the see some improvements. And as I said in my
testimony, it is so important that we convey to the provider
community the special status and nature of these drugs, and
let's recognize that the labeling is not just effective when
somebody goes and looks at the fine print, but the labeling is
the start of the process of how information about the drug is
promulgated into the community through the medical record,
through the marketing materials, and so on.
We have called for a logo to distinguish these drugs. There
may be other ways, as long as it is communicated very clearly
that these drugs are different, and that is part of what
Congress is doing, too, by creating this designation.
Mr. Pallone. All right. Thanks a lot.
Mr. Coukell. One more point.
Mr. Pallone. Sure.
Mr. Coukell. The other thing that is in the bill that we
think is important is the need to monitor how the drugs are
used when they are out there so that we have some feedback and
we know that the indication is working as intended.
Mr. Pallone. All right. Thanks.
Mr. Pitts. The chair thanks the gentleman. Now recognize
the gentleman from Illinois, Mr. Shimkus, 5 minutes for
questions.
Mr. Shimkus. Thank you, Mr. Chairman. This has been a
tremendous hearing, and I am glad I stayed. I think you see the
importance that this subcommittee puts on these issues. You-all
on the panel, turn around and just turn around and see Dr.
Woodcock is right there. Wave to her. And I want to make sure
everyone knows she stayed, and I applaud her for doing that. So
this is kind of a silly question but it is really, would you
consider you-all Facebook friends with the FDA or in a
relationship? Anyone want to answer? Are you friends or you not
even--had a friend notification out there and they didn't even
accept.
Dr. Hillan. Maybe I could speak to that because obviously
it is important that the pharmaceutical industry is regulated
by the FDA both in terms of drugs and also in diagnostics, so I
don't know we would call ourselves friends, but we are
certainly, I would say, professional colleagues that work
together.
Mr. Shimkus. Yes.
Dr. Hillan. We have had----
Mr. Shimkus. Well, the point is this only gets solved with
the people in this room. It gets solved with you at the panel,
it gets solved with the FDA, and it gets solved with the public
policy folks here, and so we have to have that communication.
We have to be in a relationship, and that is what I am taking
from this because a lot of ideas. And I couldn't believe it. I
was also looking at stuff. The Pentagon was--the groundbreaking
was September 11, 1941. The dedication was January 15, 1943. So
in this issue, these are timelines. Thirteen years to get to
one point; 15 years still down the road. We have got to switch
those timelines, and there are people who are willing to accept
some risk. And besides, we have heard numerous testimonies on
this 21st Century Cures debate and how do we do that
effectively.
The question I have by listening to the testimony is
government is historically bureaucratic and not flexible and we
are very rigid, but in this process, you are the experts, you
are the doctors, you are the scientists and stuff, how do we
write into legislation the flexibility to incentivize while
protecting public health? And can we do that? And then that is
what we are going to move on legislatively, but am I right in
that analysis and do you think we can get there? And I only
have 2 minutes left, so why don't we just go down and let
everybody weigh into that if you would like.
Dr. Hillan. So, it obviously has to be done appropriately,
but much of this is about building trust. We are working
towards the same goal of bringing forward new antibiotics to
patients. We have interacted with the FDA, and I can tell you
the FDA has really facilitated the development of plazomicin.
They came up with really good ideas, totally appropriate ideas
actually the company hadn't thought about. BARDA has been
incredibly supportive and brings technical expertise to the
table as well, so we can work effectively together and we are
all working towards the same goal. So I would hope that we can
continue to do that in the future, and it does need to be
flexible. We need to trust people to use good judgment so that
we can all look after patients.
Dr. Murray. I think one of the benefits of the PCAST report
and the new structure that there will be, will include external
stakeholders, be included, and I certainly agree with that, and
external to the government, and I think their input is needed,
and that may help keep driving the process.
Dr. Thomas. I think it is absolutely possible to write
legislation that is flexible and also impactful. I also like to
say that we want to be part of that discussion. We believe it
does take a different way of thinking, and we have to be
willing to test things that may not necessarily seem so
palatable. I just want to finish with saying it is no accident
that breast cancer is almost a curable disease today. It is no
accident that many bone marrow tumors are curable of chronic
diseases today. It is no accident that people can live with
diabetes. It is because the incentives for everyone are to
innovate in those areas. So if you don't want this to be an
accident, we need to design the right incentives.
Mr. Outterson. We need billion-dollar incentives hanging
out there for companies, big incentives, not little. It is hard
to write what you will need in 10 years, though, into
legislation when we don't know what the diseases will exactly
look like.
BARDA is a wonderful model. One of the most encouraging
things I took from yesterday from PCAST was significant
additional funding being proposed for BARDA because they can
contract, given flexibility, based on what is happening now.
The only other person who is not in this room are the pairs, so
I would like to see Blue Cross and Blue Shield, insurance
companies, Medicare, this is a pay-for-performance, pay-for-
value issue. Let's pay more to keep it valuable.
Mr. Coukell. There is no single solution here. There are
things that Congress can do now and do quickly and should do.
There are places where there needs to be continued
collaboration. I think we have seen that with FDA and companies
and stakeholders, and PCAST called for more of it. There are
more important basic science questions that are not industry
questions, are academic questions, but questions that will be
solved when we have them effectively working together not just
with more money but with smarter science, so there is no one-
size solution here, but there are things we can do now quickly
to move this along.
Dr. Powers. I think we talked a lot today about the history
of resistance and how we got to this point, and actually there
is already tremendous flexibility built into FDA's regulations
already. When FDA came out with the regulations in 1970 on what
an adequate study was, the pharmaceutical companies immediately
sued. And when it went to the courts, the courts actually found
that the regulations allowed tremendous flexibility for FDA and
how the studies can be designed.
I think what we were trying to say this morning, and Dr.
Outterson brought this point up several times, is that these
studies should actually show added value for patients, that
really what we are trying to say is if we are going to give
perks for companies, it ought to be perks for performance, not
perks for potential, that the studies should actually show, as
Dr. Hillan pointed out and how his study is designed, that the
drugs actually save lives in the people that we need to use
them in.
Mr. Shimkus. Thank you, Mr.--and thank you--a minute ago--I
want to end on this or not----
Dr. Murray. Could I add one additional comment? Would that
be----
Mr. Pitts. Yes, you may.
Dr. Murray. Thank you very much. I want to get back to the
point of BARDA being a good model, and that is a wonderful
model. NIAID could serve the parallel role of helping to
develop drugs for--thanks. That BARDA is not directly
applicable to, and they already do have an antibiotic
resistance leadership group whose path is to help design trials
for antibiotic resistance organisms, but I think the BARDA
model is a good one. It does not necessarily have to be BARDA
that would carry it out.
Mr. Shimkus. And I appreciate that. The last comment. I
just will say that these companies, I really--and Mr. Waxman
just raises my ire every now and then, too. Because it is not
perks. These guys raise capital, assume risk to try to save
lives, employ thousands of people, and pay taxes, so they are
the ones who are raising the capital and assuming a risk. So,
if we go down the route of trying to beat up corporate America
in this process, we are not going to be friends. We will be
defriended and we can't. We got to be all in this together, and
with that, I yield back my time.
Mr. Pitts. The chair thanks the gentleman. The gentleman
from Georgia wanted to make a point of clarification.
Mr. Gingrey. Mr. Chairman, thank you, and I don't disagree.
In fact, I do agree with the comments from my colleague, the
gentleman from Illinois, Mr. Shimkus, in what he just said. But
I also want to, Dr. Powers, let you know that the concerns that
you express in your testimony are not lost on me at all, and I
don't think other members of the committee, and also, the
ranking member of this health subcommittee, Mr. Pallone, and
his concerns about labeling, and that is not lost on me either.
And staff is working almost as we speak on that issue, Frank,
to try to get that right and to lay those concerns.
Mr. Chairman, this has been fabulous. You-all are great,
both panels. Dr. Woodcock, we are so grateful to you, and I,
like the other members that stayed over, and didn't get an
early flight back to Atlanta, I am grateful that I stayed
because this has been most, most informative, and we are deeply
appreciative. Thank you very much, and I yield back.
Mr. Pitts. The chair thanks the gentleman, and I would like
to say it is good to hear of the collaboration that is
occurring between the public and private sectors, and that is
so important. And I might mention, Dr. Woodcock has been before
this committee many times, and she is one administrator that
always stays through the whole hearing, and you should be
commended for that, and we thank you for your responsiveness.
Now, other members will have questions, and we will have
follow-up questions. We will send those to you. We ask that you
please respond promptly. I remind members that they have 10
business days to submit questions for the record. That means
they should submit their questions by the close of business on
Friday, October 3rd. Very good hearing, exciting, very
informative. Thank you very much for your participation.
Without objection, this subcommittee is adjourned.
[Whereupon, at 11:35 a.m., the subcommittee was adjourned.]
[Material submitted for inclusion in the record follows:]
Prepared statement of Hon. Fred Upton
Today's hearing is an important opportunity to review the
growing threat of antibiotic resistant infection--a global
health crisis. To quote the CDC: ``The loss of effective
antibiotic treatments will not only cripple the ability to
fight routine infectious diseases but will also undermine
treatment of infectious complications in patients with other
diseases.'' This public health crisis is an important topic for
us to explore as we continue our work on the bipartisan 21st
Century Cures initiative and work to bring more effective
treatments to patients more quickly.
Make no mistake: we are losing effective antibiotic
treatments because the pace of new and novel drug development
has not kept up with these organisms' ability to build
resistance to the treatments available today.
Passage of the GAIN Act in the 112th Congress as part of
our efforts to reauthorize the FDA User Fee legislation was an
important step in incentivizing antibiotic drug development,
but much work remains to be done.
Committee members Congressmen Gingrey and Green have put
forward one such idea--the Adapt Act--and I want to commend
them for their continued leadership in addressing these
important issues.
The President's own Council on Science and Technology (or
PCAST) just yesterday released a call to action on the issue of
antibiotic resistance. This plan included a number of
initiatives it intends to undertake over the next 5 years,
including incentives for the development new drugs and
diagnostic tests. We will continue to engage on this issue as
part of our bipartisan 21st Century Cures agenda.
Today's witnesses will provide important perspectives on
the types of incentives to help drive the types of new drug
development necessary to meet this growing threat and whether
such incentives might also address other areas of unmet need.
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