SILVER SPRING, Md. _ For the third day in a row, theFDA's Antiviral Drugs Advisory Committee votedfavorably for an anti-HIV drug after expressing deepconcerns about the adequacy of the clinical data.
The panel on Wednesday wrapped up its three-daysession by giving the agency the broad mandate it soughtto shift Bristol-Myers Squibb Co.'s stavudine (d4T), anucleoside analog, from accelerated approval status tofull approval but only after several complaints werevoiced about the insufficiency of evidence.
"The data are suggestive but not definitive," said LarryFreedman, a National Institutes of Health biostatistician."I would guess that this drug should be approved but it isnot our job to guess."
Bristol-Myers, of Princeton, N.J., had sought fullapproval based on a randomized, double-blind trial ofd4T against AZT (zidovudine) that cumulatively showedan improvement in CD4 cell counts.
The committee considered narrow indications for d4T,assuming full approval would be granted by the FDA.The committee split 4-to-3 on the question of whether thedrug should be labeled as, in effect, a "me-too" drug thatwas not superior to AZT. Only one member supportedand six opposed labeling d4T as superior to AZT.
But advisory committee executive secretary David Feigalurged the panel not to approve the d4T for limitedindications but to reach a consensus on whether themanufacturer had provided sufficient evidence of clinicalbenefit. Feigal reminded the panel that the manufacturerwill "still have to complete additional confirmatorystudies" regardless of whether the drug is kept inaccelerated approval or moved to full approval.
The combined "scientific and policy" agenda pushed bythe FDA bothered several advisory panel members.
"Science is supposed to guide our deliberations but theissue of access weighs heavily," noted panel memberChris Mathews, director of a San Diego AIDS clinic.Mathews dismissed accolades from several members whopraised the manufacturer for a well-conducted study.Mathews saw the fundamental problem as whether aconfirmatory trial could be constructed that wouldproduce the data the advisory committee needed to base adecision. "It is not feasible to expect patients to stay in anassigned therapy and to assign outcomes to a treatmentunequivocally," he said.
The panel's concerns about the lack of scientific evidencemeans that the drug labeling will be of criticalimportance. "We will discuss indications with the FDA,"said Lisa Dunkle, executive director of HIV clinicalresearch at Bristol-Myers. Dunkle put the best face on thepanel's interest in specific indications for the drug: "Weappreciate the importance the panel gave to makingphysicians aware of the important clinical findings."
HIV treatment advocates had urged the FDA to grantBristol-Myers full marketing approval even through theyhad concerns that the confirmatory study was too small.
Earlier this week the panel recommended acceleratedapproval for another nucleoside analog, Epivir (3TC). Italso cleared the first protease inhibitor to treat HIVdisease when it recommended accelerated approval forSaquinavir in combination with nucleoside analogs. (SeeBioWorld Today, Nov. 7, 8, 1995, p. 1.) n
-- Michele L. Robinson Washington Editor
(c) 1997 American Health Consultants. All rights reserved.