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Gilead Requests FDA Approval of Truvada for HIV Prevention

Gilead Sciences announced this week that it has submitted a supplemental New Drug Application to the U.S. Food and Drug Administration (FDA) requesting approval of a new indication for Truvada, its tenofovir/emtricitabine combination pill, for HIV pre-exposure prophylaxis (PrEP). If granted, it would be the first antiretroviral to be approved for HIV prevention.

PrEP using tenofovir with or without emtricitabine has been tested in several large trials that have reported results over the past 2 years. As described this summer at the International AIDS Society conference in Rome, the iPrEx study of gay men and the Partners PrEP and TDF2 trials of heterosexual men and women showed that once-daily Truvada PrEP dramatically reduced the risk of infection.

However, the Fem-PrEP study of daily tenofovir/emtricitabine for heterosexual women was halted early due to lack of efficacy, as was an arm of the VOICE trial testing tenofovir alone (the tenofovir/emtricitabine combination in that study is still being evaluated.)

While Truvada PrEP appears highly effective -- at least for well-selected, high-risk populations that use it as part of a comprehensive prevention strategy that also includes condoms and risk-reduction counseling -- advocates and public health officials have raised important issues regarding cost, access, long-term toxicities, and development of drug resistance.

Truvada is widely used for HIV treatment and has demonstrated long-term safety and efficacy, but concerns remain about the risk of tenofovir-related kidney problems and bone loss in susceptible patients.

“The data from these large-scale clinical trials suggest that Truvada may have a role to play in meeting the urgent public health need to reduce new HIV infections,” Gilead CEO John Martin stated in a company press release.

Citing the potential public health benefit, Gilead has requested priority review on its supplemental application. This could result in a decision as soon as June 2012. The FDA may convene an advisory committee meeting in the spring to discuss the benefits and risks of Truvada PrEP, which would include an opportunity for public commentary.

“Men who have sex with men have borne an enormous burden in this epidemic, and have also been consistently at the head of efforts to help reverse it,” stated iPrEx Protocol Chair Robert Grant in a press release issued by the iPrEX study team. "The 2499 men and transgender women who participated in the iPrEx study Brazil, Ecuador, Peru, South Africa, Thailand and the United States have made an historic contribution to the effort to help end this epidemic.”

"The efficacy results observed in the Partners PrEP trial indicate that PrEP may be an important new tool for HIV prevention among heterosexuals in serodiscordant relationships, who account for a large proportion of new HIV cases worldwide,” Partners PrEP lead investigator Connie Celum added in the Gilead press release.

Following the initial release of the iPrEx results last fall, the Centers for Disease Control and Prevention (CDC) issued interim guidance on oral tenofovir/emtricitabine PrEP for gay/bisexual men, acknowledging that some HIV negative people and their providers will likely use Truvada off-label for this purpose. The agency is currently developing formal U.S. Public Health Service guidelines for PrEP.

It is important that people who wish to use PrEP be tested for HIV before starting and regularly thereafter, since use of tenofovir/emtricitabine alone if the virus is present can lead to drug resistance that could limit future treatment options.

"The decision about whether to approve Truvada for prevention should be made with compassion, based on science rather than ideology, and without judgment regarding the behaviors of people at risk for HIV," said Project Inform director Dana Van Gorder. "We firmly believe in the right of people at risk of becoming infected with HIV to choose PrEP, which has been shown to be effective when used with condoms, as an additional method of HIV prevention."  

12/16/11

Sources

Gilead Sciences. Gilead Sciences Submits Supplemental New Drug Application to U.S. Food and Drug Administration for Truvada for Reducing the Risk of Acquiring HIV. Press release. December 15, 2011.

iPrEX Study Team. FDA Asked to Approve New HIV Prevention Method, Pre-Exposure Prophylaxis (PrEP). Press release. December 15, 2011.