The US Food and Drug Administration’s (FDA) Antimicrobial Drugs Advisory Committee
has recommended the approval of emtricitabine 200 mg and tenofovir alafenamide 25 mg tablets (F/TAF; Descovy) for pre-exposure prophylaxis (PrEP) in men and transgender women who have sex with men. The committee voted 16 to 2 to recommend approval for the alternative to emtricitabine/tenofovir disoproxil fumarate (F/TDF; Truvada).
The committee’s decision was based upon data from the phase 3 DISCOVER study, which evaluated F/TAF in comparison with F/TDF. Findings from the study, which enrolled cisgender-men who have sex with men (MSM) and transgender women who are at high risk for HIV acquisition, were presented in a late-breaking oral abstract session earlier this year at the Annual Conference on Retroviruses and Opportunistic Infections (CROI 2019
The participants received daily blinded F/TAF (200/25 mg) or F/TDF (200/300 mg), with matching placebo; the investigators conducted pill counts and analyzed blood levels to measure adherence. The primary end point of the DISCOVER study was the HIV infection rate per 100 person years when 50% completed at 96 weeks.
In total, 90% of participants completed >
48 weeks on the study with median follow-up of 84 weeks. For this analysis, 85% of the participants remained on the study drug, 6% of participants discontinued by choice, and an additional 6% of participants were lost to follow-up. Both drugs were noted to be well-tolerated with 1.5% adverse event-related discontinuations.
According to the study team, “on-study sexual HIV risk persisted with an STI rate of 99.5 per 100 person years.” Across both of the treatment arms there were 21 HIV diagnoses documented, which is an infection rate of 0.26 per 100-person years. The investigators note that this figure is significantly lower than the expected HIV infection rate for those at risk for HIV but not on PrEP in the United States.
"What we were able to determine from this study is that Descovy is non-inferior in its efficacy for PrEP compared to Truvada," Brad Hare, chief of infectious disease at Kaiser-Permanente, San Francisco, and lead presenter of the trial data at CROI 2019, told Contagion
®. "We also had some pre-specified secondary end points looking at safety parameters, specifically bone and renal safety using these drugs, and we found a significant difference between the arms that favored the Descovy product over Truvada."
The committee also evaluated pharmacokinetic data on F/TDF and F/TAF for HIV treatment and PrEP in cisgender women, a population that was not studied in the DISCOVER trial. The committee voted 10 to 8 that there was not enough data regarding the efficacy of F/TAF in this population.
It is important to note that the FDA is not bound by the committee’s recommendation, however, the feedback may be considered by the agency in making its final decision regarding approval.
“We appreciate the advisory committee’s thoughtful review and discussion of the data during today’s meeting and look forward to collaborating with FDA to make this potential new prevention option available to people at risk of HIV in the United States,” said Diana Brainard, MD, senior vice president, HIV and emerging viruses, Gilead Sciences said in a statement
issued by the company. “Descovy represents a potential new therapeutic option for people at risk of sexually acquired HIV-1 infection. If approved for a PrEP indication, Descovy could play a meaningful role in the federal initiative to address the nation’s HIV epidemic.”
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