FDA to Evaluate Lenacapavir for Prevention of HIV

The FDA has accepted new drug application (NDA) submissions for lenacapavir as pre-exposure prophylaxis (PrEP) for the prevention of HIV, Gilead Sciences announced in a release.¹ The drug also received priority review and was assigned a Prescription Drug User Fee Act (PDUFA) target action date of June 19, 2025.

Lenacapavir is a twice-yearly injectable HIV-1 capsid inhibitor with a multi-stage mechanism of action that is different from other currently approved antiviral agents. The therapy is designed to inhibit the disease at multiple stages of its lifecycle, while most antivirals only act on a single stage of viral replication. Lenacapavir is being evaluated as a long-acting option in multiple early and late-stage clinical trials.

READ MORE: HIV Treatment, PrEP Have Come a Long Way, With More Work To Be Done

“Today, we are one step closer to introducing the first-ever twice-yearly HIV prevention choice that could, if approved, help transform the landscape for individuals who need or want additional prevention options that better fit into their lives,” Dietmar Berger, MD, PhD, chief medical officer at Gilead, said in a release.¹

The NDA submissions for lenacapavir were based on positive data from the phase 3 PURPOSE 1 (NCT04994509) and PURPOSE 2 (NCT04925752) trials. The trials are part of Gilead’s PURPOSE program, which the company says is “the most comprehensive and diverse HIV prevention trial program ever conducted.” The program includes a total of 5 trials that are evaluating the safety and efficacy of lenacapavir.

PURPOSE 1 is a double-blind, active-controlled, multicenter, randomized phase 3 trial evaluating the safety and efficacy of twice-yearly, subcutaneous lenacapavir for PrEP, and once-daily oral emtricitabine 200 mg and tenofovir alafenamide 25 mg (Descovy) or once-daily oral emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg (Truvada) for the investigational use of HIV prevention in women.²

The study cohort included 5338 HIV-negative adolescent girls and young women between the ages of 16 and 25 who were sexually active with male individuals. Key exclusion criteria included prior receipt of an HIV vaccine, prior use of long-acting systemic PrEP therapy, or prior use of HIV postexposure prophylaxis therapy. Of the patients, 2134 received lenacapavir, 2136 received Descovy, and 1068 received Truvada.

Investigators found that there were 0 incident HIV infections in the lenacapavir group, 39 in the Descovy group, and 16 in the Truvada group. Compared to a background HIV incidence of 2.41 per 100 person-years in the screened population of 8094, the incidence with lenacapavir was found to be significantly lower. Lenacapavir also had a high adherence rate: 91.5% of all trial participants received on-time injections at week 26, and 92.8% received on-time injections at one year.

PURPOSE 2 is a double-blind, multicenter, randomized phase 3 study evaluating the safety and efficacy of twice-yearly subcutaneous lenacapavir for PrEP compared to background HIV incidence and once-daily oral emtricitabine and tenofovir disoproxil fumarate (Truvada) in cisgender men, transgender men, transgender women and gender non-binary individuals aged 16 years or older. The study cohort included 3295 participants from 88 sites across the world, including the US, Argentina, Thailand, Brazil, Mexico, Peru, and South Africa.³

Despite high levels of reported sexual behavior, chemsex and sexually transmitted infections among participants, the study showed that 99.9% in the lenacapavir group did not acquire HIV, with 2 incident cases among the 2180 patients. There was a 96% risk reduction from lenacapavir when compared to background HIV incidence. In the Truvada group, there were 9 incident cases among 1087 individuals, demonstrating that lenacapavir was 89% more effective.

Lenacapavir was previously awarded Breakthrough Therapy Designation for PrEP by the FDA in October 2024. Gilead said that it also recently submitted applications for the therapy to the European Medicines Agency, which will be reviewed under Accelerated Assessment Review Timeline.

“We’re excited about the potential of lenacapavir to make a real difference in HIV prevention in the US and around the world, supporting the broader goal of ending the HIV epidemic for everyone, everywhere,” Berger said in the release.¹

READ MORE: HIV Resource Center

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References

1. U.S. FDA Accepts Gilead’s New Drug Applications for Twice-Yearly Lenacapavir for HIV Prevention Under Priority Review. News Release. Gilead. February 18, 2025. Accessed February 18, 2025. https://www.gilead.com/news/news-details/2025/us-fda-accepts-gileads-new-drug-applications-for-twice-yearly-lenacapavir-for-hiv-prevention-under-priority-review

2. Full Efficacy and Safety Results for Gilead Investigational Twice-Yearly Lenacapavir for HIV Prevention Presented at AIDS 2024. News Release. Gilead Sciences. July 24, 2024. Accessed February 18, 2025. https://www.gilead.com/news-and-press/press-room/press-releases/2024/7/full-efficacy-and-safety-results-for-gilead-investigational-twice-yearly-lenacapavir-for-hiv-prevention-presented-at-aids-2024

3. Gilead Presents Full PURPOSE 2 Data Results for Twice-Yearly Lenacapavir for HIV Prevention at HIV Glasgow. News Release. Gilead. November 13, 2024. Accessed February 18, 2025. https://www.gilead.com/news/news-details/2024/gilead-presents-full-purpose-2-data-results-for-twice-yearly-lenacapavir-for-hiv-prevention-at-hiv-glasgow