After an all-day meeting that stretched into the evening, the FDA's Antiviral Drugs Advisory Committee (ADAC) voted to recommend approval of Gilead Sciences Inc.'s HIV drug Truvada to prevent infection in adults at high risk of contracting the disease.

The panel voted 19-3 in favor of Truvada (emtricitabine/tenofovir disoproxil fumarate) for pre-exposure prophylaxis (PrEP) for HIV-uninfected men who have sex with men; 19-2 with one abstention for uninfected partners in serodiscordant couples; and 12-8 with two abstentions for other individuals at risk for acquiring HIV through sexual activity.

Panel member Laura W. Cheever, deputy associate administrator and chief medical officer at the HIV/AIDS Bureau at the Department of Health and Human Services cited the "excellent data" and "need to move the dial forward," though she voted against Truvada's PrEP use in the third group because the drug has not shown efficacy in all populations to date.

Gilead's supplemental new drug application has a PDUFA date of June 15, and, if approved, it would become the first pill for HIV prevention.

Rates of new HIV infection have stayed the same over the past two decades, about 50,000 per year. And "existing interventions have not reduced the number of new HIV infections," noted John Mellors, chief of the division of Infectious Disease at the University of Pittsburgh and member of Gilead's scientific advisory board. "New medicines are needed."

But the vote did not come without controversy. During the public comment period, AIDS advocates overwhelmingly objected to Truvada as a prophylaxis, arguing that a preventive drug would result in increased risky sexual behavior. And the AIDS Healthcare Foundation, which recently blasted the state of California for granting $11 .8 million on HIV/AIDS research funding to Gilead to study expanded use of Truvada, has criticized the danger of drug side effects and low adherence rates for the daily drug, which could translate into increased rates of infection.

Indeed, adherence was a major topic of discussion for the panel, with the point driven home by the clinical data presented by study investigators. Results from the University of Washington-sponsored Partner PrEP study, which enrolled 4,785 serodiscordant couples (in which one has HIV and one does not) in Kenya and Uganda, showed a reduction in HIV infection of 73 percent. And data from a second study, iPrEx showed that the risk of HIV in uninfected men who have sex with other men fell by 42 percent overall. (See BioWorld Today, July 14, 2011.)

But subsets of patients who had sufficient concentration levels of the drug in their blood showed that the reduction rates jumped to more than 90 percent in both trials. That means many subjects were not taking the drug as indicated. The FDA even noted that poor adherence to daily Truvada was not significantly different than receiving placebo.

"It's hard to uncouple adherence from efficacy," noted Doris B. Strader, associate professor of medicine at the University of Vermont College of Medicine, who voted no against two of the three indications.

But Thomas P. Giordano, assistant professor of medicine at Baylor College of Medicine, argued that the panel's charge is not to judge adherence. "Our charge is to judge whether the drug works."

Opponents also were concerned about risk compensation, the idea that subjects on Truvada PrEP will increase risky behavior because they feel they're protected by the drug. iPrEx investigator Robert Grant, of the Gladstone Institute at the University of California, San Francisco, reported that patients on trial actually decreased risky behavior.

"Taking a pill every day [offered] a daily reminder," he said, though he later added that there was a chance of "social desirability bias" on that self-reported evaluation.

Several panel members said they voted in favor of Truvada on the basis that they would be able to recommend a strict risk evaluation and mitigation strategy (REMS) that would ensure that patients being given Truvada PrEP were HIV-negative and that subjects on the prophylaxis therapy would be monitored for resistance. Votes on REMS, HIV testing and monitoring and postmarketing requirements occurred after press time Thursday.

Reports of renal impairment associated with the tenofovir disoproxil fumarate ingredient also came up for discussion – it's also an expected topic during Friday's ADAC meeting on Quad, Gilead's four-drug, single-tablet regimen, which comprises the two components of Truvada plus evitegravir and boosting agent cobicistat. (See BioWorld Today, May 10, 2012.)

Truvada, which gained approval in managing HIV in 2004, pulled in revenues of $2.88 billion in 2011. Should the FDA approve the PrEP indication next month, the "challenge remains on the commercial side," Piper Jaffray analyst Ian Somaiya wrote in a research note, adding that the "opportunity is likely to be modest and difficult to track."

Shares of Gilead (NASDAQ:GILD) gained 61 cents Thursday to close at $51.25.