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NIH GP-160 PANEL SUGGESTS LARGE SIMPLE TRIALS WITH MULTIPLE AIDS VACCINES; TWO MORE MEETINGS ON DoD FUNDING OF MICROGENESYS VACCINE TRIAL PLANNED

Executive Summary

A large simple trial studying multiple AIDS vaccines is a possible use of the $20 mil. congressional appropriation to the Department of Defense to study MicroGeneSys' gp-160 vaccine, a National Institutes of Health panel suggested Nov. 5. NIH Director Bernadine Healy, MD, who convened the panel, told the group that "your task is to inject scientific judgment where it is lacking and to provide an objective assessment of gp-160 and any of the other candidate vaccines. Your recommendations will provide the basis for the response that I will submit to Congress." The panel will meet again in two or three weeks, and the issue is scheduled for discussion at the NIH Advisory Committee to the Director on Dec. 2. Under the 1993 DOD appropriations legislation, the $20 mil. will be "obligated" to DoD to conduct a Phase III trial with MicroGeneSys' VaxSyn HIV-1 vaccine in people with HIV unless NIH, FDA and DoD inform Congress, within six months, that trials are not warranted for gp-160 and that other AIDS research should be pursued by DoD with the money ("The Pink Sheet" Oct. 5, T&G-1). Although NIH will not be conducting the studies, the agency would like a say in how the funding will be spent. Healy has taken umbrage at Congress' decision to fund gp-160 without scientific guidance. Healy noted that NIH "was asked to participate in this process in an unusual way. We were not asked to help identify the best vaccine or vaccines for research funding, we were asked to comment on the Congress' predetermination of gp-160 as a vaccine worthy of federal support." The concept of a large, simple therapeutic vaccine trial was raised by Mark Harrington, Treatment Action Group. The actual structure of such a trial was presented by National Institute of Allergy and Infectious Diseases researcher Susan Ellenberg, PhD. She said a large, simple therapeutic vaccine trial should include sero-positive patients; multiple vaccine candidates; a placebo control for the vaccine; a study time span of three to five years; and a primary endpoint that is clinical. Ellenberg noted that similar trials have been conducted successfully with cardiovascular drugs. Addressing the use of clinical endpoints, Ellenberg elaborated on the problems associated with using CD4 cell counts as a surrogate marker in therapeutic vaccine trials. In particular, Ellenberg asserted that the "lack of CD4 patterns with therapeutic vaccines" and the modest "effect on CD4 trajectory" will provide "inadequate indicators" of clinical effect. She recommended instead that for early stage patients, the onset of "the first AIDS defining event or death" might serve as an endpoint and, for later stage patients, "mortality would be a primary endpoint." Ellenberg also presented various patient sample sizes, indicating that a study with five-year follow-up would require 14,000 individuals and a trial with two-year follow-up would need an enrollment of approximately 30,000 people. While panel members were mostly supportive of the concept of a large, simple trial, they did raise several logistical concerns. Fred Robbins, MD, Case Western Reserve University, stated: "The approach is a reasonable one [but] we have to be prepared to the fact that it may not work." He continued: "We can learn a lot if we do the immunology and if we make the proper observations. At the end of it we will know more even if we end up with a vaccine that isn't very effective." Concern about a manufacturer's ability to provide vaccines for a 30,000-patient trial was raised by Upjohn Chairman Theodore Cooper, MD/PhD. Cooper noted that the accelerated timetable would place pressure on the sourcing of any one or all immunogens, suggesting that "we would have to get started on it quite soon." Addressing concerns that new drugs developed and used by patients during a long vaccine trial may alter the endpoints, TAG's Harrington argued that "concerns about new drugs on endpoints are valid." However, he noted, "I wish there were marvelous new drugs bursting out over the horizon every six months but there aren't, and if there are, we can change our protocol to incorporate them."
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