[Letter to Robert C. Byrd from Harold Varmus and David Kessler]

01-21-94 04:7PM FROM OASPA NEWS DIV TO 916199424979001/002 $ r" /DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service t4 National Institutes of Health Bothosda, Maryland 20 892 JAN -4 1994 The Honorable Robert C. Byrd Chairman, Committee on Appropriations United State Senate Washington, DC 20510 Dear Mr. Chairman: This letter is intended to serve as a certification by the undersigned that the large-scale Phase III clinical investigation of the gpl60 vaccine should not proceed. Our reasons for that determination follow. The National Institutes of Health (NIH) convened a Panel in November of last year to consider whether or not the "large-scale Phase Ill clinical investigation (of gpl60] should proceed," as directed by the Department of Defense Appropriations (DOD) Act, 1993. There were important considerations that were included in those deliberations. First, there was an assumption that the appropriated funds were inevitably going to be spent on a large-scale efficacy trial of the gpl60 vaccine candidate. Second, the Panel assumed that if such a trial was to be implemented, it was important to express, in their best scientific judgement, how such a trial should be conducted. In this context, the recommendations of the Panel, which were widely reported, were as follows: 1) based on traditional scientific criteria, currently available scientific information on gpl60 by itself cannot be considered adequate for deciding to go forward with a large-scale clinical efficacy trial; and 2) assuming that the appropriated funds were going to be expended on a clinical trial including gpl60, the funds should be used for a large-scale clinical efficacy trial to study several products. Because ongoing discussions during the past year may have caused some confusion concerning our opinion in this matter, the following clarification may be useful. If one begins with the assumption that the question of the conduct of a largescale efficacy trial of a gpl60 candidate is indeed an open question, then our intent must be restated. Based on the current state-of-tho-art in therapeutic vaccine research, the NIH and Food and Drug Administration (FDA) cannot recommend, on a scientific basis, that a large-scale efficacy trial of a single therapeutic vaccine be conducted with public funds at this time. We feel that the funds in question could more appropriately be used to answer basic questions about the immune response and host defense mechanisms related Lo vaccines prior to initiating large-scale human trials of a therapeutic vaccine. This research could include the conduct of smaller Phase I and Phase II trials of multipln vaccine candidates. The DOD could expand these studies, if scientifically indicated, and initiate additional studies on promising products. A decision to carry out a large-scale efficacy trial at a later dat should be based on the knowledge accrued from the basic research mentioned above as well as from the results of the ongoing clinical trials. As you know, the DOD has a long history of conducting vaccine trials that have led to the licensure of a number of vaccines for infectious diseases of interest to their mission. In addition, they have established infrastructure IIIII II I I I VIII IIIll IIII II II II III IIIII 5571095.0446.020

01-21-94 94:57PM FROM OASPA NEWS DIV TO 916199424979 P002/002 Page Two--The Honorable Robert C. Byrd fur vaccine trials around the world; in particular, the DOD has established infrastructure in Thailand, a location well-suited to the trials of promising HIV vaccine candidates. Therefore, the DOD is in an excellent position to address those issues which capitalize on their strengths in vaccine research. The NIH and FDA stand ready to share their expertise and knowledge to complement the DOD research efforts. A similar letter is being sent to Representative William Natcher. Harold Varmus, M.D. Director National Institutes of Health Sincerely yours, David Ke sler,.D. Commissioner Food and Drug Administration