Food and Drug Administration
Center for Drug Evaluation and Research
Claudia H. Kawas, M.D., Chair
Jerry S. Wolinsky, M.D.
Robert Temple, M.D.
Russell Katz, M.D.
Armando Oliva, M.D.
Ranjit Mani, M.D.
Anuja M. Patel, M.P.H.
Steven Ebert, Pharm. D. (Consumer Representative)
Gerald van Belle, Ph. D.
Mary Ganguli, M.D., M.P.H.
Karl D. Kieburtz, M.D., M.P.H
Jorge C. Kattah, M.D.
Roger J. Packer, M.D.
Industry Representative (Non-Voting)
Daniel Azarnoff , M.D.
summary minutes for the
I certify that I attended the
Anuja M. Patel, M.P.H Claudia Kawas, M.D.
Executive Secretary Chair
At , the meeting was called to order by Claudia Kawas, M.D., Chair. This was followed by the conflict of interest statement, read by Anuja M. Patel, M.P.H., Executive Secretary, and the introduction of meeting participants.
Open Public Hearing Speaker:
· Barry A. Cooper, MHA
Companion Care Association, Inc.
Discussions on new drug application (NDA) 21-487, memantine hydrochloride, Forest Laboratories, Inc., indicated for the treatment of moderate to severe dementia of the Alzheimer’s type.
· Opening Remarks and Russell Katz, M.D.
Overview of Issues Director, Division of Neuropharmacologic Drug Products, FDA
· Introduction and
Memantine Overview Executive Vice President,
· Memantine Pharmacology J. Timothy Greenamyre, M.D., Ph.D
Co-Director, Center for Neurodegenerative Disease,
· Efficacy Data Lon S. Schneider, M.D.
Professor of Psychiatry, Neurology, and Gerontology,
· Memantine Safety and Tolerability Jeffrey Jonas, M.D.
Safety Vice President, CNS
Forest Research Institute
· Summary and Risk/Benefit Steven T. DeKosky, M.D.
Professor and Chair, Department of Neurology;
Director, Alzheimer’s Disease Research Center,
FDA Presentation Ranjit Mani, M.D.
Medical Reviewer, Division of Neuropharmacological Drug Products, FDA
Questions for Advisory Committee
1. Has the population for which the use of memantine is proposed been adequately identified in the studies included in this application?
YES – 8 No – 0
The Committee felt that the population was adequately identified given that the population was defined by using the Mini-Mental State Exam (MMSE) scale. Individual members expressed concern over certain limitations of individual studies such as the body of evidence on severe Alzheimer’s disease patients in the Latvian study was small and the arbitrariness of the scales applied to each study.
YES – 8 No - 0
The Committee felt that the key studies in this
application are adequate for evaluating efficacy of memantine for the proposed
indication. However, individual members expressed concern in identifying the
key studies. The Committee felt that the
· In particular, are the instruments used to evaluate efficacy in these studies appropriate for patients with moderate-to-severe Alzheimer’s Disease?
YES – 8 No -0
The Committee felt that the instruments were reasonably appropriate for population studied in that they were state of the art at the time of the studies. However, individual members expressed the opinion that the instruments should be improved in the future. Two global measures that are similar for the measure being studied should not be used; rather, a cognitive measure and a global measure should be applied in the future. In the long-term, more appropriate measures such as combining two different measures as oppose to similar measures should be explored.
3. Has substantial evidence of the effectiveness of memantine for the proposed indication been demonstrated by the studies included in this application?
YES – 8 No –0
The Committee felt that the evidence of the effectiveness of memantine for the proposed indication has been demonstrated by the studies included in this application. The data should be further studied. Individual members expressed concern over the varying evidence of effectiveness and small effect size among the studies.
YES – 8 No -0
The Committee felt that evidence of the safety of memantine for the proposed indication was demonstrated. However, individual members expressed concern related to the long-term issue when applied to larger population, drug interactions, and data shown in animal models. Additional information for combining cholinesterase inhibitors with memantine should be explored in the future.
The Chair stated, prior to adjourning, that although the votes were unanimous, several members of the Committee expressed concerns and reservations. Members expressed difficulty in identifying the key studies in evaluating efficacy of memantine; furthermore, members suggested that more appropriate measures such as combining two different measures as oppose to similar measures should be explored when evaluating efficacy in Alzheimer’s disease patients. Overall, additional data should be collected regarding the long-term effectiveness of memantine when applied to a larger population and its drug interactions should be further explored.
Following completion of discussion of the questions, the committee adjourned at approximately .
Anuja M. Patel, M.P.H.
Peripheral and Central Nervous System Drugs Advisory Committee