BETHESDA, MD. _ The National Institute of Allergy andInfectious Diseases' AIDS Research Advisory Committee(ARAC) on Friday voted against initiating a large-scaleefficacy trial to study two leading AIDS vaccines.Immediately following the meeting, NIAID directorAnthony Fauci told reporters that he accepts and agreeswith ARAC's recommendation.Although Fauci said the move did not represent a setbackfor AIDS vaccine research, the decision means that it couldbe two or three years before a Phase III clinical trial of anAIDS vaccine is initiated.ARAC members debated data from animal studies, Phase Iand Phase I/II pilot trials with Genentech Inc.'s gp120soluble envelope vaccine (mimics the outer envelope of theAIDS virus) and a similar vaccine developed by BiocineClinical Research, a joint venture between Chiron Corp.and Ciba-Geigy. Their conclusion: the data is notsufficiently promising to justify expending the enormousfinancial and social resources needed to carry out a 10,000-patient Phase III clinical trial comparing the Genentech andBiocine vaccines to a placebo. (See the June 7 issue ofBioWorld Today, p. 1, for more details on AIDS vaccinetrials.)"We don't want to abandon soluble envelope vaccines butwe're not prepared to test them singly in a Phase III trial,"said Fauci. He said it might make more sense to wait andcompare the envelope vaccine concept to newertechnologies which lag behind it clinically, such as viralvectors.After more than nine hours of deliberations, 23 ARACmembers (four members abstained and others were absent)voted in favor of offering the following advice to Fauci:"Continue current gp120 progress and development ofother candidates currently under study. Proceed withexpanded clinical trial evaluation when another conceptand/or compelling data from current or other studies areavailable."By recommending against expanded clinical trials at thecurrent time, ARAC effectively recommended that no newgp120 vaccine clinical trials be initiated for an indefiniteperiod. Phase I and I/II trials currently in progress will becompleted and analyzed.Representatives from South San Francisco-basedGenentech and Biocine presented arguments to ARACabout the need for a large-scale trial using their products.Genentech's AIDS vaccine project leader Donald Francistold ARAC that even if a Phase III trial proved the productdidn't work, it would be a major scientific advance. Thecore of his argument was that no more could be learnedfrom additional animal and pilot human testing of thevaccine.But ARAC members disputed the notion that the onlyuseful information left to gather about these vaccines mustcome from a large Phase III trial. They argued that resultsfrom ongoing chimpanzee and human studies have not yetbeen fully analyzed. Specifically, recently reported cases ofHIV infections in five patients who had received partialdoses of gp120 vaccine have not yet been fully studied.Researchers believe the infections have no link to thevaccines.Members of AIDS advocacy groups who testified duringthe public comment portion of the meeting noted thecomplex social and political ramifications of a large-scalevaccine trial for a product that might not work. Theywarned that without broad and deep community support forsuch a trial, enrolling the necessary numbers of gay menand intravenous drug users would be nearly impossible."The envelope concept at this point in time is not viable interms of community support and preparedness," said Fauci."A diverse and knowledgeable group of people have saidit's not worth a large efficacy trial."ARAC's recommendation conflicts with that of NIAID'sVaccine Working Group (VWG), which met last April todiscuss laboratory, animal and clinical trial results of thegp120 candidate vaccines. The VWG concluded that thegp120 data supported expanded clinical studies. But severalVWG members told ARAC that the recommendation waslukewarm, at best.Fauci said the two recommendations are complementary.He said that VWG correctly concluded that, in order todefinitively establish gp120 efficacy, expanded trials wereneeded. He said ARAC concurred that a large-scale trialwas the only way to definitively establish efficacy, but thatthe products weren't compelling enough to justify theexpense and effort.Officials estimated a 9,000- to 10,000-patient trial wouldcost between $20 and $40 million, funds not currentlycontained in NIAID's fiscal 1995 proposed budget. n

-- Lisa Piercey Washington Editor

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