Updated: FDA committee recommends Truvada’s approval as PrEP

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The U.S. Food and Drug Administration (FDA) Antiviral Drugs Advisory Committee recommended Thursday that the supplemental application for Gilead Sciences’ HIV drug Truvada (a combination of emtricitabine plus tenofovir, or TDF-FTC) as pre-exposure prophylaxis (PrEP) be approved for high-risk, HIV-negative individuals to reduce the risk of sexually acquired HIV infection.

A slide showing the results from various Truvada PrEP Phase 2B/3 HIV prevention trials.

The panel of medical experts, people living with HIV/AIDS and community advocates voted to decide if the current application supports a favorable risk-benefit assessment adequate to approve Truvada for a PrEP indication in three populations. For HIV uninfected men who have sex with men (MSM) the panel voted 19-3 in favor; for HIV uninfected partners in serodiscordant couples (where one partner is HIV infected and the other is not) the panel voted 19-2 in favor with one abstention; and for other individuals at risk for acquiring HIV through sexual activity 12 voted in favor, eight against with two abstentions.

“The third vote for ‘others at-risk’ was kind of close, but I’m ok with that. We don’t yet have a specific trial that addresses Truvada’s use among people outside of discordant couples or high-risk MSM,” said Dr. Veronica Miler, director of the Forum for Collaborative HIV Research. “Although, in the end, if it’s approved for the first two populations, it will be prescribed for people outside of a discordant relationship, too.”

Miller said there was also some contention on the panel about requiring an HIV-negative test when getting the prescription filled. “The prescriber should make sure the patient has an HIV-negative test. That’s the level where it needs to be done. It can’t be policed. The FDA can’t require that level of control at the point of distribution of the drug,” Miller said.

An impressive group of HIV experts gathered at the FDA White Oak campus in Maryland to review data from various studies that showed the protective benefit of daily oral administration of Truvada for the committee. Gilead applied for a six-month priority review of its application, which it was granted due to the drug’s potential for providing significant improvement in the protection of HIV infection and that there is no other drug product on the market with an indication for HIV prevention. 

“Those of us who were involved in the trials and who interact with people at risk for HIV do not think that TDF-FTC is a panacea, but we do believe that culturally-tailored programs that combine chemoprophylaxis with behavioral and/or social-structural interventions can make a difference,” said Kenneth Mayer, MD, principal investigator of the Fenway Health trail site of the iPrEx study.  Discussed in depth at Thursday’s committee meeting, iPrEx found that daily oral dosing of Truvada among high-risk MSM indicated a 44 percent reduction in the incidence of HIV. Detectable levels of the study drug in participants’ blood strongly correlated with the prophylactic effect, with high adherence boosting protection up to 92 percent. In 2011 the Centers for Disease Control and Prevention (CDC) posted interim guidelines for the use of Truvada as PrEP for high-risk MSM in response to the iPrEx results.

“Advocates can challenge pharma and funders about costs, but the science suggests that the judicious use of the medication can decrease HIV incidence. For some people, that additional help may keep them uninfected during a vulnerable period. It is time to reflect and to think about how to ensure that PrEP can assist the momentum to curb the epidemic,” Mayer said.

The committee’s recommendation to the FDA is not binding, but often followed. During the open public hearing portion of the meeting, more than 40 people gave their opinion to the committee – a substantial number of whom spoke on behalf of the AIDS Healthcare Foundation (AHF). Robert D. Elliott, RN Care Manager at AHF, argued that risk compensation was too real and too risky to make PrEP available at a population level. A final FDA decision is expected by June 15.

“Our challenge now is to understand how to use PrEP effectively to tackle HIV incidence worldwide,” said Chris Collins, amfAR’s vice president and director of public policy, in a press release. “PrEP is certainly not for everyone, but delivered in a targeted way and as part of a comprehensive approach that includes other evidence-based interventions like AIDS treatment, condoms, education, syringe exchange, and male circumcision, PrEP may play an important role in beginning to end the AIDS epidemic.”

AIDS advocacy group AVAC issued a press release Friday urging the FDA to follow the committee’s recommendation, and giving four recommendations for moving forward:

  • Create public health guidance via the CDC, the World Health Organization (WHO), and other agencies on the appropriate use of Truvada as PrEP in different populations and settings.
  • Continued research to answer urgent questions such as how best to implement PrEP, how to provide PrEP safely and efficiently, how to integrate PrEP with other essential prevention interventions such as condoms, and how to ensure high levels of adherence.
  • Donor and government support of investment in PrEP research and initiatives.
  • Additional research to test PrEP in other populations, such as injection drug users, and to evaluate new drugs and less frequent PrEP dosing schedules. 

The Risk Evaluation and Mitigation Strategy (REMS)
The main arguments against providing Truvada as PrEP include fears of risk compensation – where an individual engages in risky sexual behavior once on the prophylactic – and development of resistance to the drug if the patient does not take the pill as indicated.  Side effects from Truvada, including liver toxicity, are also of concern.  Truvada is already FDA approved for HIV treatment, so doctors can prescribe the drug for “off-label use” for HIV prevention. But, advocates argue, expanding the approval to include prevention for HIV-negatives might ensure the drug is used more safely and effectively.

Gilead Sciences agreed to provide various materials to providers and patients as part of the Risk Evaluation Mitigation Strategy (REMS), which included a notification letter to health care providers (HCPs) on the details of PrEP, full prescribing information, a medication guide with every bottle of Truvada, a training guide for HCPs, a prescriber safety brochure, an individual safety brochure, and a Truvada wallet card (all available online and hardcopy). Gilead also offered free HIV and HBV testing, free condoms, subsidized HIV-1 resistance testing to individuals who seroconvert, and a Medication Assistance Program for Truvada for a PrEP indication for individuals who lack prescription coverage. Safety data on Truvada for PrEP also will be collected as part of the existing routine vigilance program.

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