Joint Meeting of the Nonprescription Drugs
Advisory Committee
and the Endocrinologic & Metabolic Drugs
Advisory Committee
This
is the final report of the Joint Meeting of the Nonprescription Drugs Advisory
Committee and the Endocrinologic & Metabolic Drugs Advisory Committee held
on
All
external requests should be submitted to the Freedom of Information office.
_________________________________________________________________________________________
The Nonprescription Drugs Advisory Committee and the
Endocrinologic & Metabolic Drugs Advisory Committee of the Food and Drug Administration, Center for Drug Evaluation and
Research, met jointly on
Alastair
Wood, M.D. chaired the meeting.
Nonprescription Drugs Advisory Committee (voting):
Alastair Wood, M.D. (Chair), Neal Benowitz, M.D. ,
Terrence F. Blaschke, M.D., Leslie Clapp, M.D.,
Ernest B. Clyburn, M.D., Frank F.
Davidoff, M.D.,
Endocrinologic & Metabolic Drugs Advisory Committee (voting):
Sonia Caprio, Thomas O. Carpenter,
M.D., Dean A. Follmann, Ph.D., Michael R. McClung, M.D., David S. Schade, M.D.,
Morris Schambelan, M.D., Nelson B. Watts, M.D., Margaret E. Wierman, M.D., Paul
D. Woolf, M.D.
Special Government Employee (SGE) Consultants (voting):
Richard A. Neill, M.D., James
Schultz (patient representative)
Government Employee (voting):
Susan Makris, Ph.D.
Industry Representative (non-voting):
Steven W. Ryder, M.D.
FDA Speakers:
Karen Davis-Bruno, Ph.D., Charles Ganley, M.D., Michael Koenig, Ph.D., Mary
Parks, M.D., Laura Shay, RN, M.S., C-ANP, Daiva Shetty, M.D.
FDA Participants:
Jonca Bull, M.D., Charles Ganley, M.D., John Jenkins, M.D., Robert Meyer,
M.D., David Orloff, M.D., Mary Parks, M.D., Curtis Rosebraugh, M.D.
Open Public Hearing Speakers (
James McKenney, PharmD - National
Lipid Association
Stewart S. Levy, R. Ph. - Impact
Health
Robin Edison, M.D., MPH
Dr. Boisey
Barnes - Association of Black Cardiologists, Inc.
Sidney M. Wolfe, M.D. -
Public Citizen's Health Research Group
Alice Rein, M.S. - National
Consumer League
Penny M. Kris-Etherton, Ph.D.,
R.D. -
William L. Greene, Pharm.D., BCPS, FASHP - American Society of Health-System
Pharmacists
Tracy Hankin - WebMD
Bob Dufour - Walmart
Jan Engle, - American Pharmacists
Association
Laurie Tansman - Mt Sinai NYU
Health
Christopher Maus - Lifestreams
Technologies, Inc.
These summary minutes for the
January 13 and 14, 2005 of the Joint Meeting of the Nonprescription Drugs
Advisory Committee and the Endocrinologic & Metabolic Drugs Advisory
Committee of the Food and Drug Administration were approved on
I certify that I attended the
January 13 and 14, 2005, Joint Meeting of the
Nonprescription Drugs Advisory Committee and the Endocrinologic & Metabolic
Drugs Advisory Committee of the Food and Drug Administration meeting and that
these minutes accurately reflect what transpired.
________//S//____________________ ________//S//____________________
Hilda F. Scharen, M.S. Alastair
Wood, M.D.
Executive Secretary Chair
On both days, the committees
considered the safety and efficacy of new drug application (NDA) 21-213,
proposing over-the-counter (OTC) use of Mevacor 20 mg a day, (lovastatin),
Merck & Co., Inc., to help lower LDL “bad” cholesterol, which may prevent a
first heart attack.
Alastair
Wood, M.D. (Committee Chair), called the meeting to order at
Introduction Mary
Parks, M.D., Deputy Director
Regulatory History and Overview Division of Metabolic and
Endocrinologic Drug Products
of Current Proposed OTC Program Office of Drug
Evaluation II
Sponsor
Presentations:
Introduction Edwin
Hemwall, Ph.D., Vice President
Worldwide
Regulatory and Scientific Affairs
Johnson &
Johnson / Merck Consumer Pharmaceuticals
Rationale for OTC Lovastatin Richard
Pasternak, M.D. – VP, Clinical Research
Merck Research
Labs
Mevacor OTC
Self Management System Jerry
Hansen, RPh - Vice President Business Development and Consumer Research,
Johnson & Johnson / Merck Consumer Pharmaceuticals
Actual Use
Study Results Robert
Tipping, M.S.
Director, Biostatistics
Merck Research Labs
Medical
Perspective and Conclusion Jerome
D. Cohen, M.D., FACC, FACP
Professor of Internal
Medicine/Cardiology
Director, Preventive Cardiology
Programs
FDA Presentations:
Reproductive and Fetal Toxicity Karen
Davis-Bruno, Ph.D.
Division
of Metabolic and Endocrinologic Drug Products
Office
of Drug Evaluation II
Label
Comprehension Study Laura
Shay, RN, M.S., C-ANP
Division
of Over-the-Counter (OTC) Drug Products
Office of Drug Evaluation V
CUSTOM – Actual Use Study Daiva
Shetty, M.D.
Division
of Over-the-Counter (OTC) Drug Products
Office of Drug Evaluation V
Nonprescription Simvastatin Michael
Koenig, Ph.D.
in the
Office of Drug Evaluation V
The meeting was
adjourned at approximately
Alastair
Wood, M.D. (Committee Chair), called the meeting to order at
Open Public Hearing
Presentations
Questions to the Committee:
1. Taking
into consideration the efficacy data from the AFCAPS/TexCAPS and EXCEL studies,
plus any additional information provided by the sponsor, please respond to the
following questions:
a.
Does the
proposed target population merit treatment with a statin to lower cholesterol
and thereby reduce heart disease risk?
Yes: 24
No: 0
Abstain: 0
Discussion: The subcommittee agreed the proposed target population
would benefit from treatment with a statin to lower cholesterol and reduce
heart disease, along with improved diet and exercise.
b. Has the sponsor provided
adequate rationale for the use of a fixed dose of lovastatin 20 mg to lower
cholesterol and heart disease risk in this population? Is this an effective
dose to reduce cholesterol in this population?
Yes: 24
No: 0
Abstain: 0
Discussion: The subcommittee discussed that this study assumes
adherence to the label. In addition, the members emphasized that there is not
enough data, especially for Over-The-Counter use, of the efficacy of a 20mg
dose versus usual care.
2. Lovastatin
and other statins cause elevation in hepatic transaminase serum levels of
unknown clinical significance in individuals with normal baseline hepatic
function.
a.
Does the
Committee think that pretreatment baseline liver function tests are required
prior to starting lovastatin therapy?
Yes: 0
No: 24
Abstain: 0
b. Are the liver function tests
necessary during administration?
Yes: 0
No: 24
Abstain: 0
Discussion: Some members underlined that baseline liver function
tests (LFT) should be required before administration of lovastatin 20 mg. Other
committee members also felt that LFT should be required during therapy, for
continued safe use of the drug.
The committee members
generally found that the risk of liver toxicity with statins seems to be
similarly low and were not excessively concerned about patients with
undiagnosed liver problems taking Mevacor Daily.
3. Statins
have been associated with the development of serious muscle toxicity. Furthermore, drug-drug interactions with
lovastatin may increase the risk of muscle toxicity. Is the risk of muscle toxicity with
lovastatin 20 mg acceptable for an OTC drug; as applied to the population
indicated in the label?
Yes: 24
No: 0
Abstain: 0
Discussion: The subcommittee argued that the study indicated problems
in the self-selection of patients for use of lovastatin, which may cause some
safety concerns.
4. Lovastatin
and other statins are currently labeled as Pregnancy Category X (the drug
should not be used during pregnancy).
Have you heard data that suggests to you that the drug is not so
potentially toxic to the fetus to prevent its marketing OTC under any
circumstance?
Yes: 18
No: 5
Abstain: 0
Is the label adequate for this group?
Yes: 0
No: 24
Abstain: 0
Discussion: The subcommittee discussed that the CUSTOM study is not
a good representation of the general population, especially for women of
child-bearing age who might take Mevacor.
Some members indicated that the drug comparison study included drugs not
comparable to Mevacor. The members added that some of the drugs used in this
study are not Over-The-Counter and are used only under Physician’s care, such
as Epinephrine.
The members
highlighted that the label advising against use of the drug during pregnancy or
while trying to become pregnant, should include consequences, such as how
significant the risk of damage may be to the fetus. In addition, the members
were concerned that women who were unaware that they were pregnant would take
Mevacor and possibly damage the developing fetus.
The Committee
recognized it is difficult to estimate the risks of birth defects, as well as
be able to correlate animal drug studies to humans. The members concluded that
the data presented is not conclusive enough to extrapolate risk versus benefit
to an OTC situation.
Taking into consideration the results from
the CUSTOM actual use study:
5. Does
the frequency of appropriate self-diagnosis and self selection support the
conclusion that lovastatin 20 mg can be used safely and effectively in the OTC
setting? Please describe which analysis
influenced your decision.
Yes: 5
No: 18
Abstain: 0
Discussion: The members felt they did not have insight into the
population that self-selected and used inappropriately; this information would
be critical as product understanding comes from the users. Thus, the committee
added that the label comprehension study should be made a part of the actual
use study.
Some members
emphasized that the information needed to self-manage, while taking Mevacor, is
too complex to reduce to an understandable level for the general population. In
addition, the members discussed that the CUSTOM study literacy level was higher
than that of the general population.
The committee
indicated that there is a need for more organized tests to test what is
critical information and reduce confusion. The members concluded that the
self-diagnosis results of the CUSTOM study did not support that lovastatin 20
mg can be used safely and effectively in the OTC setting.
6. A
high percentage of study subjects in the CUSTOM actual use study relied upon a
physician for correct self-selection and/or self-diagnosis.
a. Do you expect the general population will
have this degree of health care provider interaction?
Yes: 2
No: 16
Abstain: 5 (Those who abstained from
voting felt that there was not enough information available to answer this questions.)
b. Do the CUSTOM actual use
study results support a conclusion that individuals can use lovastatin 20 mg
safely and effectively in the OTC setting without the guidance of a
physician?
Yes: 3
No: 20
Abstain: 0
Discussion: The committee members pointed to the fact that close to
two-thirds of the patients were not among the intended population for treatment
with the statin and that a high percentage of patients relied upon a physician
for correct self-selection and/or self-diagnosis to start treatment with
lovastatin.
Some members
abstained from voting because they did not feel they had enough information to
extrapolate the degree of interaction of subjects with their health care
provider to the general population.
Although the
committee members criticized the CUSTOM study, they praised Merck for its
efforts to bring the statin to Over-The-Counter and encouraged the company to
continue its efforts, as a means to address the enormous and growing
cardiovascular public health problem in the country.
The committee
concluded that based on patients’ inability to self-select for treatment and to
comply with long-term use and testing, individuals could not safely and
effectively use lovastatin in the OTC setting.
7. Do
the results regarding self management (i.e. user behavior after the initiation
of treatment) raise any concerns about the safe and effective use lovastatin 20
mg in the OTC setting? If yes, what are
the concerns? Please consider in your
discussion: monitoring LDL-C, physician interaction, new risk factors or
medication after initiation of therapy.
Yes: 23
No: 0
Abstain: 0
Discussion: The subcommittee expressed some concerns of potential
drug interactions with the use of lovastatin. In addition, the members the
study presented was not conclusive enough to indicate adequate self-monitoring
of individuals taking 20 mg lovastatin. Some members added that patients with
low income and no insurance would be unlikely to get LDL tests, which would
make it difficult to recognize any new conditions these individuals may have.
Based on all the information provided:
8. Should
Mevacor OTC be marketed OTC for the proposed target population?
a. If no, why not?
b. If yes, why?
c. If yes, do you think Mevacor
OTC is safe and effective for use in the OTC setting without the
"self-management system"?
Yes: 3
No: 20
Abstain: 0
Discussion: The members argued that making Mevacor more easily
available would help get needed treatment to millions of Americans at moderate
risk of heart disease that needed to lower cholesterol levels.
The committee felt that the safety
and benefits of Mevacor are well-established, but was concerned that the wrong
people might take it if available in an OTC setting, especially after an
aggressive advertising campaign.
The members expressed worry that
patients will skip necessary doctor visits or inaccurately determine the drug
is for them, while forgoing important advice about changing diet and exercise
in order to control their elevated level of cholesterol.
The committee concluded that the
Health Care System is currently not designed for such OTC use of statins and
individuals could not operate in this system effectively. The concerns
expressed by the members stemmed that this may set precedence for approval for
other “silent” diseases drugs, such as anti-diabetic or high blood pressure
drugs, to go OTC while the infrastructure is not adequate to support this.
Some committee members expressed
interest in seeing an in-between option in an OTC setting, where patients could
buy the drug without a prescription but only after speaking with a pharmacist;
such an option is available in
Finally, the committee praised
Merck in the efforts to address the needs of individuals without health
insurance, who should also have the right to have treatment with statins. In
addition, the members felt that FDA and Merck need to work together to bring
more effective and cost effective drugs to an OTC setting.
The meeting was
adjourned at approximately