[Conference Materials, Panel to Review GP-160 Vaccine Candidate (1992: Bethesda, Maryland)]

National Institutes of Health PANEL TO REVIEW GP-160 VACCINE CANDIDATE Thursday, November 5, 1992 15571095.0463.0031111111111111111111111111111 5571095.0463.003

PRINCIPLES REGARDING THE CONGRESSIONAL APPROPRIATION OF FUNDS FOR THERAPEUTIC GP-160 VACCINE TRIALS We welcome the convening of an NIH-sponsored panel which will evaluate therapeutic HIV vaccines currently in clinical trials and suggest ways to proceed in regard to the congressional appropriation. These discussions and subsequent actions by the NIH, FDA and DOD must be guided by the following principles: 1) The primary and overriding purpose of the panel must be to develop, without delay, a large trial to assess the effects of several vaccine products on clinical progression and mortality in HIV-positive individuals. A randomized and comparative large trial, in which entry criteria are broad and data collection is simplified, may be able to establish, by the virtue of its vast sample size, whether gpl60 or any other appropriate vaccine candidate provides clinical benefits to people with HIV disease. 2) The large trial must include individuals with CD4 counts of all levels and must not exclude concomitant antiviral therapy. The structuring of the trial, including the selection of sites, must ensure that a diverse population (where women, people of color, intravenous drug-users, gay men, people with hemophilia, and adolescents are appropriately represented) can participate. Extensive virological or immunological studies must be done only on a subset of study participants. 3) The selection of the immunogens for the trial should be decided upon by January 15, 1993 and enrollment of the study should begin by March 15, 1993. 4) The current paucity of therapeutic options demands a quick and clear answer to the question of the usefulness of active immunotherapy in HIV infection. We will not tolerate any unnecessary delays due to bureaucratic infighting, "turf wars," or a rehashing of the manner in which the DOD appropriation was secured. 5) The NIH, FDA and DOD must work together to develop a comprehensive, creative and ambitious program to develop and test therapeutic vaccines. This should include clinical trials to test envelope vaccines, core protein vaccines, DNA vaccines, whole killed virus vaccines, combinations using different HIV epitopes and strains as well as promising

vectors and adjuvants. Congressional intervention would not have happened if the NIH had not systematically ignored immune-based therapies, including vaccination of HIVpositive individuals, for so many years while pioneering work was done outside of NIH-funded efforts. ACT UP/Boston ACT UP/Golden Gate ACT UP/LA ACT UP/NY ACT UP/Philadelphia AIDS Action/Baltimore AIDS Treatment News Being Alive-People with AIDS and HIV Action Coalition of LA Committee of Ten Thousand Critical Path AIDS Project Gay Men's Health Crisis Latino Commission on AIDS People with AIDS Coalition-New York Project Inform--San Francisco Treatment Action Group (TAG)

National Institutes of Health PANEL TO REVIEW GP-160 VACCINE CANDIDATE Thursday, November 5, 1992 A committee of experts has been convened by Dr. Bernadine Healy, Director of the National Institutes of Health to review the scientific data available on the GP-160 vaccine candidate, in response to the recently passed Fiscal Year 1993 Department of Defense language. The committee is charged with evaluating the following: M What is the current scientific assessment of the MicroGeneSys GP-160 vaccine candidate as a therapeutic agent? SBased on the scientific merit of the GP-160 vaccine, should a large-scale efficacy trial be initiated at this time in HIV seropositive individuals? SSince no formal protocol is available at this time, what should be the role of the NIH over the next six months in reviewing potential protocol designs? SShould consideration be given to including several promising vaccine candidates in a large-scale comparative efficacy trial? Are additional candidates ready for Phase III testing? What would be the objective, rational and optimum design of such a comparative trial?

REMARKS* BY BERNADINE HEALY, M.D.** GOOD AFTERNOON, AND THANK YOU FOR SETTING ASIDE YOUR OTHER RESPONSIBILITIES ON RATHER SHORT NOTICE TO ATTEND THIS MEETING. I HAVE CONVENED THIS MEETING UNDER THE AUTHORITIES OF THE NATIONAL INSTITUTES OF HEALTH'S ADVISORY COMMITTEE TO THE DIRECTOR. WE HAVE COME TOGETHER TODAY TO DISCUSS THE MANDATE THAT THE NIH RECENTLY RECEIVED FROM THE CONGRESS TO DETERMINE THE SCIENTIFIC MERITS OF GP-160, A DRUG THAT MAY PROVE TO BE EFFECTIVE IN TREATING INDIVIDUALS WHO ARE INFECTED WITH THE HIV VIRUS. *PRESENTED TO THE NIH PANEL TO REVIEW GP-160 VACCINE CANDIDATE, NOVEMBER 5, 1992. **DIRECTOR, NATIONAL INSTITUTES OF HEALTH, BETHESDA, MARYLAND.

AFTER I DISCUSS THE CHARGE TO THE NIH, THE COMMISSIONER OF THE FOOD AND DRUG ADMINISTRATION, DR. DAVID KESSLER, WILL EXPLAIN HIS AGENCY'S ROLE AS MANDATED BY THE RECENTLY SIGNED DEPARTMENT OF DEFENSE APPROPRIATION (P.L. 102-396). As THE LETTER THAT DR. MOSKOWITZ SENT YOU EXPLAINS, THE DEPARTMENT OF DEFENSE APPROPRIATION MANDATES THAT FEDERAL DOLLARS BE SPENT TO LAUNCH A MAJOR EFFICACY TRIAL IN HIV SEROPOSITIVE INDIVIDUALS OF A POTENTIAL AIDS THERAPEUTIC VACCINE, GP-160. IT IS IMPORTANT TO NOTE THAT THE CHARGE TO STUDY THIS PARTICULAR VACCINE WAS NOT PLACED IN STATUTE BECAUSE GP-160 HAS PROVEN TO BE SUPERIOR TO OTHER CANDIDATE VACCINES OR BECAUSE OF SOME OTHER COMPELLING SCIENTIFIC OR MEDICAL IMPERATIVE. IT IS THE SPECIFIC ROLE OF THIS PANEL -- OF ALL OF YOU 2

GATHERED HERE TODAY -- TO MAKE THAT CRUCIAL DETERMINATION ABOUT THE SCIENTIFIC MERITS OF GP-160. IN BRIEF, THE ROLE OF THIS PANEL WILL BE TO PUT THE BRAKES ON THIS EFFICACY TRIAL, AS DESCRIBED IN THE LEGISLATION, IF -- AND ONLY IF -- YOU DECIDE THAT THE SCIENTIFIC MERITS OF GP-160 ARE NOT COMPELLING ENOUGH TO MAKE IT A WORTHY CANDIDATE VACCINE FOR AN EFFICACY TRIAL THAT WOULD BE SUPPORTED BY $20 MILLION OF U.S. TAXPAYERS' MONEY. AS MANY OF YOU KNOW, THE NIH WAS ASKED TO PARTICIPATE IN THE PROCESS IN A RATHER UNUSUAL WAY. WE WERE NOT ASKED TO HELP IDENTIFY THE BEST VACCINE OR VACCINES FOR RESEARCH FUNDING, BUT RATHER WE WERE ASKED TO COMMENT ON THE CONGRESS'S PREDETERMINATION OF GP-160 AS A VACCINE WORTHY OF FEDERAL SUPPORT. THUS, THE NIH WAS TAKEN OUT OF ITS USUAL ROLE OF DECIDING WHICH THERAPIES AND STUDIES, FROM A SCIENTIFIC 3

AND ETHICAL STANDPOINT, SHOULD RECEIVE FEDERAL SUPPORT. INSTEAD, WE HAVE BEEN PUT IN THE UNUSUAL -- AND UNPRECEDENTED -- POSITION OF DETERMINING WHETHER A SPECIFIC RESEARCH PROJECT, MANDATED BY LEGISLATION, IS INDEED WORTHY OF FEDERAL SUPPORT. ONE MIGHT SAY THAT IT IS A CASE OF THE TAIL WAGGING THE DOG. I KNOW THAT MANY OF YOU SHARE MY CONCERNS ABOUT THE UNUSUAL AND UNPRECEDENTED POSITION IN WHICH THE NIH FINDS ITSELF. AND, LIKE MANY OF YOU, I ALSO HAVE CONCERNS AND DEEP RESERVATIONS ABOUT THE PROCESS BY WHICH GP-160 WAS SELECTED BY THE CONGRESS FOR THE PROPOSED EFFICACY TRIAL. NOT ONLY IS THIS A CASE OF LAW PREEMPTING SCIENCE AND SCIENTIFIC JUDGMENT, IT IS A CASE OF LAW PREEMPTING SCIENCE IN THE CONTEXT OF A CLINICAL TRIAL INVOLVING HUMAN SUBJECTS. I AM SURE THAT MANY OF YOU SHARE MY CONCERNS ABOUT THE PRECEDENT THAT SUCH A PREEMPTION MAY SET. 4

UNDERPINNING ALL CLINICAL RESEARCH INVOLVING HUMANS IS THE PRINCIPLE DERIVED FROM THE HIPPOCRATIC OATH AND UNDERSCORED IN THE BELMONT REPORT REQUIRING PHYSICIANS TO BENEFIT THEIR PATIENTS "ACCORDING TO THEIR BEST JUDGMENTll -- PRESUMABLY THAT MEANS THEIR BEST JUDGMENT BASED ON SCIENTIFIC FACT, NOT LEGISLATIVE MANDATE. FROM THE MOST CYNICAL POINT OF VIEW, IT WOULD APPEAR THAT THE CONGRESS HAS SIGNED AN UNINFORMED CONSENT FORM FOR PATIENTS WITH AIDS. LET US BEAR IN MIND, HOWEVER, THAT THE CONGRESS' MOTIVATION IN PASSING THIS LEGISLATION IS THE SAME MOTIVATION THAT DRIVES ALL OF AIDS RESEARCH -- THE DESIRE TO FIND A CURE FOR THIS DEVASTATING DISEASE. THUS, I HOPE THAT, LIKE ME, YOU WILL WHOLEHEARTEDLY ENDORSE THE SPIRIT, IF NOT THE LETTER, OF THIS NEW LAW. 5

LET ME DISCUSS THE LETTER OF THIS NEW LAW. THIS PARTICULAR AMENDMENT IS UNIQUE IN TWO WAYS: FIRST, THE DIRECTIVE IS WRITTEN IN LAW -- NOT JUST IN REPORT LANGUAGE, THUS REMOVING THE OPPORTUNITY FOR DISCRETION ON THE PART OF THE EXECUTIVE BRANCH. AND SECOND, THE APPROPRIATION BILL REQUIRES THAT A SPECIFIC COMMERCIAL PRODUCT BE TESTED. THAT IS WHERE THE NIH -- WHERE ALL OF YOU -- COME INTO PLAY. THIS MEETING WILL INITIATE THE PROCESS BY WHICH THE SCIENTIFIC MERITS OF GP-160 WILL BE DETERMINED. YOUR TASK IS TO INJECT SCIENTIFIC JUDGMENT WHERE IT WAS LACKING AND TO PROVIDE AN OBJECTIVE ASSESSMENT OF GP-160 AND OF ANY OTHER CANDIDATE VACCINES. YOUR RECOMMENDATIONS WILL PROVIDE THE BASIS FOR THE RESPONSE THAT I WILL SUBMIT TO THE CONGRESS. I HOPE TO PRESENT YOUR RECOMMENDATIONS -- EITHER IN INTERIM OR FINAL 6

FORM -- AT THE NEXT MEETING OF THE NIH ADVISORY COMMITTEE TO THE DIRECTOR ON DECEMBER 2ND. I MUST EMPHASIZE THAT, DESPITE THE CONCERNS THAT WE MAY HAVE ABOUT THE PROCESS BY WHICH GP-160 WAS SELECTED BY THE CONGRESS, IT IS ABSOLUTELY IMPERATIVE THAT THIS PANEL GIVE GP-160 AN OBJECTIVE AND FAIR ASSESSMENT. MY OTHER CHARGE TO YOU TODAY IS TO DISCUSS AND MAKE COMMENTS AND RECOMMENDATIONS ON A NUMBER OF SPECIFIC ISSUES. THESE ISSUES ARE ENUMERATED IN DR. MOSKOWITZ'S LETTER TO YOU. I WILL GO THROUGH THEM WITH YOU NOW: 1. WHAT IS THE CURRENT SCIENTIFIC ASSESSMENT OF THE MICROGENESYS GP-160 VACCINE CANDIDATE AS A THERAPEUTIC AGENT? 7

2. BASED ON THE SCIENTIFIC MERIT OF THE GP-160 VACCINE, SHOULD A LARGE-SCALE EFFICACY TRIAL BE INITIATED AT THIS TIME IN HIV SEROPOSITIVE INDIVIDUALS? 3. SINCE NO FORMAL PROTOCOL IS AVAILABLE AT THIS TIME, WHAT SHOULD THE ROLE OF NIH BE OVER THE NEXT SIX MONTHS IN REVIEWING POTENTIAL PROTOCOL DESIGNS? 4. SHOULD CONSIDERATION BE GIVEN TO INCLUDING SEVERAL PROMISING VACCINE CANDIDATES IN A LARGESCALE, COMPARATIVE EFFICACY TRIAL? ARE ADDITIONAL CANDIDATES READY FOR PHASE III TESTING? WHAT WOULD BE THE OBJECTIVE, RATIONALE, AND OPTIMUM DESIGN OF SUCH A COMPARATIVE TRIAL? ALL OF THESE ISSUES FOR DISCUSSION MUST BE DRIVEN BY THE PROCESS OF OBJECTIVE SCIENTIFIC 8

PEER REVIEW. IN DISCUSSING THESE ISSUES TODAY, PLEASE BEAR IN MIND THE FINAL GOAL: THAT NIH PROVIDE AN OBJECTIVE ASSESSMENT OF THE SCIENTIFIC MERITS OF GP-160. ALSO BEAR IN MIND THE WORDS OF SOPHOCLES: "A MAN WHO DEALS IN FAIRNESS WITH HIS OWN -- HE CAN MAKE MANIFEST JUSTICE IN THE STATE."2 PLEASE WORK TODAY TO ENSURE THAT WHAT IS FAIR AND JUST IS MADE MANIFEST IN FEDERAL SUPPORT OF AIDS RESEARCH. THANK YOU. 9

REFERENCES 1. THE BELMONT REPORT: ETHICAL PRINCIPLES AND GUIDELINES FOR THE PROTECTION OF HUMAN SUBJECTS OF RESEARCH, REPORT OF THE NATIONAL COMMISSION FOR THE PROTECTION OF HUMAN SUBJECTS OF BIOMEDICAL AND BEHAVIORAL RESEARCH, DEPARTMENT OF HEALTH AND HUMAN SERVICES, APRIL 18, 1979. 2. SOPHOCLES, ANTIGONE, TRANSLATION BY ELIZABETH WYCKOFF (EMPHASIS BY THE AUTHOR). 10

Building 31, Conference Room 10 9 IMMI-" i Amitabhc Maxumn& Corey Karen Galdenthcd Ora David Lawrence Anita Scum Kathryn Enrique Diana Daniel Jane Frederic Stickland Rogers Brawn Taylor Yusuf Loan Mendez Wara Hloth Henney Robbins ji\IJDDDDDDDE [ 1110c David JoHo L IIuarfino Samuel Sandy Lance John David Bernadine Charles Anthony Jay John Duane Brodler Clharblee lionta Diggs Kessler Healy Crenter Faud Moskowitz Mahoney Alexander Theodore cer F I I Entrance

MEETING AGENDA 1. 2. 3. 4. 5. 6. 7. Introduction Current Status of Therapeutic HIV Vaccine Research Investigator Perspective of gpl60 Background on gpl60 Deliberations of Vaccine Working Group Discussion of Questions Conclusion and Follow-up Dr. Healy Dr. Hoth Dr. Valentine Dr. Corey Dr. Bolognesi Group Dr. Fauci Dr. Carpenter

Fiscal Year 1993 Department of Defense Appropriations Act (P.L. 102-396) Excerpt from the Bill Provided further, That $20,000,000 of the funds appropriated in this paragraph may be made available in the Acquired Immune Deficiency Syndrome program element only for a large-scale Phase III clinical investigation of the GP-160 vaccine: Provided further, That the funds referred to in the preceding proviso may be obligated unless, within six months after the date of the enactment of this Act, the Secretary of Defense, the Director of the National Institutes of Health, and the Commissioner of Food and Drugs submit to the Committees on Appropriations of the Senate and House of Representatives a written certification containing a determination of such officials that the largescale Phase Ill clinical investigation should not proceed, the reasons for that determination, and an assessment of the GP-160 vaccine: Provided further, That if such certification is presented, the Secretary of Defense may use these funds only for other AIDS research needs of the Department of Defense; and the Senate agree to the same.

MEETING AGENDA 1. 2. 3. 4. 5. 6. 7. Introduction Current Status of Therapeutic HIV Vaccine Research Investigator Perspective of gpl160 Background on gpl60 Deliberations of Vaccine Working Group Discussion of Questions Conclusion and Follow-up Dr. Healy Dr. Hoth Dr. Valentine Dr. Corey Dr. Bolognesi Group Dr. Fauci Dr. Carpenter

Fiscal Year 1993 Department of Defense Appropriations Act (P.L. 102-396) Excerpt from the Bill Provided further, That $20,000,000 of the funds appropriated in this paragraph may be made available in the Acquired Immune Deficiency Syndrome program element only for a large-scale Phase III clinical investigation of the GP-160 vaccine: Provided further, That the funds referred to in the preceding proviso may be obligated unless, within six months after the date of the enactment of this Act, the Secretary of Defense, the Director of the National Institutes of Health, and the Commissioner of Food and Drugs submit to the Committees on Appropriations of the Senate and House of Representatives a written certification containing a determination of such officials that the largescale Phase III clinical investigation should not proceed, the reasons for that determination, and an assessment of the GP-160 vaccine: Provided further, That if such certification is presented, the Secretary of Defense may use these funds only for other AIDS research needs of the Department of Defense; and the Senate agree to the same.

DEPART' IENT OF HEALTH & HUMAN SERVICES Public Hew,,iu i National Institutes of f-, Bethesda, Maryland 2092 Charles C.J. Carpenter, M.D. Professor of Medicine [C 7 Brown University The Miriam Hospital 164 Summit Avenue Providence, Rhode Island 02906 Dear Dr. Carpenter: The Fiscal Year 1993 Department of Defense (DOD) Appropriation (P.L. 102-396) identifies $20 million for AIDS research and specifically states that the funds may be used for GP-160 vaccine trials unless "the Secretary of Defense, the Director of the National Institutes of Health, and the Commissioner of Food and Drugs submit to the Committees on Appropriations of the Senate and House of Representatives a written certification containing a determination of such officials that the large-scale Phase III clinical investigation should not proceed, the reasons for that determination, and an assessment of the GP-160 vaccine." In response to this directive, Dr. Bernadine Healy, Director, lii is convening a meeting of outside experts, the Food and Drug Administration (FDA) and the DOD to provide recommendations to the NIH Advisory Committee to the Director (ACD) regarding the scientific merits of a large-scale clinical investigation of the MicroGeneSys GP-160 vaccine candidate in HIV seropositive individuals. Specifically, we would like you to consider the following questions in formulating your advice: 1. What is the ourrent scientific assessment of the MicroGeneSys -GP-160 vaccine candidate as a therapeutic agent? 2. Based on the scientific merit of the GP-160 vaccine should a large-scale efficacy trial be initiated at this time in HIV seropositive individuals? 3. Since no formal protocol is available at this time, what should be the role of NIH over-the next six months in reviewing potential protocol designs? 4. Should consideration be given to including several promising vaccine candidates in a large-scale comparative efficacy trial? Are additional candidates ready for Phase III testing? What would be the objective, rationale and optimum design of such a comparative trial?

Page 2 As you are aware, the meeting will be held on November 5, 1992 from 2:00-6:00 on the NIH Campus, Building 31, Conference Room 10. I have attached a copy of the agenda and a book of briefing materials. Please understand that there will be follow-up meetings. The recommendations, interim or final, will be 'presented to the ACD on December 2, 1992. If you have any questions please feel free to call me at 301-496-3152. Sincerely, Jay Mosk witz, Ph. Associat Director for Science olicy and Legislation Attachments

National Institutes of Health PANEL TO REVIEW GP-160 VACCINE CANDIDATE Thursday, November 5, 1992 A committee of experts has been convened by Dr. Bernadine Healy, Director of the National Institutes of Health to review the scientific data available on the GP-160 vaccine candidate, in response to the recently passed Fiscal Year 1993 Department of Defense language. The committee is charged with evaluating the following: SWhat is the current scientific assessment of the MicroGeneSys GP-160 vaccine candidate as a therapeutic agent? - Based on the scientific merit of the GP-160 vaccine, should a large-scale efficacy trial be initiated at this time in HIV seropositive individuals? SSince no formal protocol is available at this time, what should be the role of the NIH over the next six months in reviewing potential protocol designs? SShould consideration be given to including several promising vaccine candidates in a large-scale comparative efficacy trial? Are additional candidates ready for Phase III testing? What would be the objective, rational and optimum design of such a comparative trial?

gp 160 Meeting ROSTER Anthony S. Fauci, M.D., Chair Director National Institute of Allergy and Infectious Diseases National Institutes of Health Building 31, Room 7A03 Bethesda, Maryland 20892 301/496-2263 301/496-4409 FAX Charles C. J. Carpenter, M.D., Co-Chair Professor of Medicine Brown University The Miriam Hospital 164 Summit Avenue Providence, Rhode Island 02906 401/331-8500 x4025 401/331-8501 FAX Duane Alexander, M.D. Director National Institute of Child Health and Human Development National Institutes of Health Building 31, Room 2A03 Bethesda, Maryland 20892 301/496-3454 301/402-1104 FAX Samuel Broder, M.D. Director National Cancer Institute National Institutes of Health Building 31, Room 11A48 Bethesda, Maryland 20892 301/496-5615 301/402-0338 FAX

gp 160 roster Lawrence S. Brown, Jr., M.D., M.P.H. Senior Vice President and Director Division of Medical Services, Evaluation and Research The Addiction Research and Treatment Corporation 22 Chapel Street Brooklyn, New York 11237 718/260-2917 718/522-3186 FAX Daryl A. (Sandy) Chamblee, J.D. Senior Policy Advisor and Counselor to the Director Office of the Director National Institutes of Health Shannon Building, Room 103 Bethesda, Maryland 20892 301/496-2122 301/402-1759 FAX Theodore Cooper, M.D., Ph.D. Chairman of the Board and CEO The Upjohn Company 7000 Portage Road Kalamazoo, Michigan 49001 616/323-7094 616/323-6780 FAX Lawrence Corey, M.D. Professor, Laboratory Medicine Microbiology and Medicine Head, Virology Division Pacific Medical Center University of Washington 1200 12th AVenue South, Room 9301 Seattle, Washington 98144 206/326-4177 206/326-4178 FAX Martin Delaney (Invited) Project Inform 1965 Market Street San Francisco, California 94103 415/558-8669 Project Inform 415/332-6240 (H) or 415/332-0184 (H) 415/558-0684 FAX

gp 160 roster 3 Susan Ellenberg, Ph.D. Chief, Biostatistics Research Branch Division of AIDS National Institute of Allergy and Infectious Diseases National Institutes of Health Solar Building, Room 2B-27 6003 Executive Boulevard Bethesda, Maryland 20892 301/496-0694 301/480-5703 FAX Karen L. Goldenthal, M.D. Acting Director Division of Biological Investigational New Drugs Center for Biologics Evaluation Research Food and Drug Administration 7500 Standish Place, Suite 250 North Rockville, Maryland 20855 301/295-8419 301/295-8466 FAX William R. Harlan, Jr., M.D. Associate Director for Disease Prevention Office of the Director National Institutes of Health Building 1, Rm 260 Bethesda, Maryland 20892 301/496-1508 301/402-2517 FAX Mark Harrington Treatment Action Group (TAG) 611 East 11th Street, Apartment 7A New York, New York 10009 212/353-8430 (H) 212/353-8430 FAX David D. Ho, M.D. Director Aaron Diamond AIDS Research Center 455 1st Avenue, 7th Floor New York, New York 10016 212/725-0018 212/725-1126 FAX

gp 160 roster 4 Daniel F. Hoth, M.D. Director Division of Acquired Immunodeficiency Syndrome National Institute of Allergy and Infectious Diseases National Institutes of Health Solar Building, Room 2A18 6003 Executive Boulevard Bethesda, Maryland 20892 301/496-0545 301/402-1505 FAX [phone] FAX Amitabha Mazumder, M.D. (Invited) Associate Professor of Medicine Director, Bone Marrow Transplantation Georgetown University Lombardi Cancer Center 3800 Reservoir Road, N.W. Washington, D.C. 20007 202/687-8330 202/687-5507 FAX Frederick C. Robbins, M.D. University Professor Emeritus Dean Emeritus School of Medicine Case Western Reserve University 10900 Euclid Avenue Cleveland, Ohio 44106-4945 216/368-3713 216/368-3970 FAX David E. Rogers, M.D. Professor of Medicine Cornell University Medical College 1300 York Avenue, Room A-127 New York, New York 10021 212/746-5431 212/746-8670 FAX John Ruffin, Ph.D. Associate Director for Minority Programs Office of the Director National Institutes of Health Shannon Building, Room 260 Bethesda, Maryland 20892 301/402-1366 301/402-2517 FAX

gp 160 roster 5 Luis G. Santiago Treatment and Data Committee ACT UP, New York 135 West 29th Street 10th Floor New York, New York 10001 201/848-2950 212/989-1797 FAX Ora L. Strickland, Ph.D., R.N., F.A.A.N. Professor Nell Hodgson Woodruff School of Nursing Chair, Independence Foundation Research Emory University 531 Asbury Circle Atlanta, Georgia 30322 404/727-7941 404/727-0536 FAX Anita D. Taylor (Invited) Director of Public Policy and Education National Minority AIDS Council 300 I Street, NW, Suite 400 Washington, DC 20002 202/544-1076 202/544-0378 FAX Diana W. Wara, M.D. Professor of Pediatrics Director, Pediatric Immunology/Rheumatology Director, Pediatric Clinic Research Center University of California, San Francisco Box 0105, Room M-601 505 Parnassus Avenue San Francisco, California 94143 415/476-2865 415/476-3466 FAX Salim Yusuf, MBBF, DPhil, FRCP (UK), FRCPC, FACC Professor, Department of Medicine McMaster University and Director, Division of Cardiology Hamilton General Hospital-McMaster Clinic 237 Barton Street East Hamilton, Ontario CANADA L8L 2X2 416/527-7327 416/521-1551 FAX

gp 160 roster 6 Kathryn C. Zoon, Ph.D. Director Center for Biologics Evaluation and Research Food and Drug Administration Building 29, Room 130 8800 Rockville Pike, HFB-1 Bethesda, Maryland 20892 496-3556 402-0763 FAX

gp 160 roster Ex Officio (Non-voting) Jay Moskowitz, Ph.D., Executive Secretary Associate Director for Science Policy and Legislation Office of the Director National Institutes of Health Shannon Building, Room 103 Bethesda, Maryland 20892 301/496-3152 301/402-1759 FAX John W. Diggs, Ph.D. Deputy Director for Extramural Research Office of the Director National Institutes of Health Shannon Building, Room 144 Bethesda, Maryland 20892 301/496-1096 301/402-3469 FAX Jane E. Henney, M.D. Deputy Commissioner for Operations Food and Drug Administration 5600 Fishers Lane, Room 1471 Rockville, Maryland 20855 301/443-2400 301/443-3100 FAX Lance A. Liotta, M.D., Ph.D. Deputy Director for Intramural Research Office of the Director National Institutes of Health Shannon Building, Room 114 Bethesda, Maryland 20892 301/496-1921 301/402-0027 FAX John D. Mahoney Associate Director for Administration Office of the Director National Institutes of Health Shannon Building, Room 102 Bethesda, Maryland 20892 301/496-4466 301/402-0279 FAX

gp 160 roster 8 Ex Officio (Continued) Enrique Mendez, Jr., M.D. Assistant Secretary of Defense for Health Affairs Department of Defense The Pentagon, Room 3E346 Washington, D.C. 20301-1200 703/697-2112 703/614-3537 FAX

gp 160 Meeting Presenters Dani P. Bolognesi, Ph.D. James B. Duke Professor and Director Center for AIDS Research Duke University Medical Center LaSalle Street Extension, Room 204 P.O. Box 2926 Durham, North Carolina 27710 919/684-3103 919/684-4288 FAX Fred T. Valentine, M.D. Professor of Medicine Department of Medicine Division of Infectious Diseases New York University Medical Center 550 First Avenue New York, New York 10016 212/263-6401 or 212/263-6565 212/263-8264 FAX [phone] FAX

[ )LPARTMI"ENT OF HEALTH & HUMAN SERVICES Public tH,,tc "uI National Institutes of.. Bethesda, Maryland 20t92 Charles C.J. Carpenter, M.D. Professor of Medicine T 2 8 Brown University The Miriam Hospital 164 Summit Avenue Providence, Rhode Island 02906 Dear Dr. Carpenter: The Fiscal Year 1993 Department of Defense (DOD) Appropriation (P.L. 102-396) identifies $20 million for AIDS research and specifically states that the funds may be used for GP-160 vaccine trials unless "the Secretary of Defense, the Director of the National Institutes of Health, and the Commissioner of Food and Drugs submit to the Committees on Appropriations of the Senate and House of Representatives a written certification containing a determination of such officials that the large-scale Phase III clinical investigation should not proceed, the reasons for that determination, and an assessment of the GP-160 vaccine." In response to this directive, Dr. Bernadine Healy, Director, I1Hi is convening a meeting of outside experts, the Food and Drug Administration (FDA) and the DOD to provide recommendations to the NIH Advisory Committee to the Director (ACD) regarding the scientific merits of a large-scale clinical investigation of the MicroGeneSys GP-160 vaccine candidate in HIV seropositive individuals. Specifically, we would like you to consider the following questions in formulating your advice: 1. What is the ourrent scientific assessment of the MicroGeneSys GP-160 vaccine candidate as a therapeutic agent? 2. Based on the scientific merit of the GP-160 vaccine should a large-scale efficacy trial be initiated at this time in HIV seropositive individuals? 3. Since no formal protocol is available at this time, what should be the role of NIH over the next six months in reviewing potential protocol designs? 4. Should consideration be given to including several promising vaccine candidates in a large-scale comparative efficacy trial? Are additional candidates ready for Phase III testing? What would be the objective, rationale and optimum design of such a comparative trial?

Page 2 As you are aware, the meeting will be held on November 5, 1992 from 2:00-6:00 on the NIH Campus, Building 31, Conference Room 10. I have attached a copy of the agenda and a book of briefing materials. Please understand that there will be follow-up meetings. The recommendations, interim or final, will be 'presented to the ACD on December 2, 1992. If you have any questions please feel free to call me at 301-496-3152. Sincerely, Jay Mosk witz, Ph.. Associat Director for Science olicy and Legislation Attachments

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutes of Health OP 14 EAL