WASHINGTON -- The AIDS drug ddC on Tuesday became thefirst drug to receive FDA advisory committee approval basedon surrogate markers for an indication for which there alreadyis an approved therapy.
The Antiviral Drug Products Advisory Committee voted 8-2 torecommend accelerated approval of dideoxycytidine as acombination therapy with AZT, the only approved drug for thedisease.
But the panel also voted against use of Hoffmann-La RocheInc.'s ddC as a single agent for patients who cannot tolerate orfail to respond to Burroughs Wellcome's AZT.
It voted 8-2, with two abstentions, against recommending ddCas a monotherapy for patients who cannot tolerate or fail torespond to AZT and 7-3, with one abstention, againstrecommending ddC as a monotherapy for patients who cannottolerate or fail to respond to both AZT and Bristol-MyersSquibb Co.'s ddI (dideoxyinosine).
Committee members said the trial data did not give compellingevidence of ddC's efficacy as a monotherapy and did notaddress the proposed population of patients who did nottolerate or failed to respond to AZT.
However, Donald Abrams, assistant director of the AIDSActivities Division of San Francisco General Hospital, noted thatseveral studies in progress address this population, including aPhase II/III study of ddI vs. ddC in 467 patients who did nottolerate or failed to respond to AZT. The trial is scheduled toend in September.
Abrams said he is "concerned" that the FDA did not seekinterim data from this trial.
The monotherapy was fragmented among several studies, noneof which were convincing by themselves, said Rochespokesman Paul Oestreicher. But "in our view the totality of thedata supported our claims," he said.
Members recommended accelerated approval of ddC ascombination therapy based on surrogate marker data showingelevated levels of CD4 cells. "I was very much impressed withthe prolongation and height of CD4 rises," said Fred Valentine, aprofessor in the Department of Medicine at New YorkUniversity Medical Center. "It seems to be an ideal situation forthe accelerated approval because we have this preliminarydata that I think is convincing. And most important, properclinical trials are under way to evaluate combination therapy."
Several trials of ddC as a combination therapy, involving 4,300patients, will provide clinical outcomes for the surrogatemarkers, Abrams said. Several committee members warnedagainst jeopardizing the completion of trials by requestinginterim data.
FDA Commissioner David Kessler and Roche officials bothexpressed a desire for quick negotiation of what is likely to bea lengthy and detailed label. "We will expedite it, but the taskis a complex one," Kessler said. He noted that the newaccelerated approval regulations allow the FDA to require acompany to submit its advertising prior to approval to speedup the process.
-- Kris Herbst BioWorld Washington Bureau
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