Editor’s Note: On September 12, Gilead Sciences announced promising interim results from a pivotal Phase III trial evaluating the efficacy of Lenacapavir, a twice-yearly injectable HIV-1 capsid inhibitor, for the prevention of HIV infection. Lenacapavir reduced HIV infection rates by 96% compared to the background HIV infection rate (bHIV). Of the 2,180 participants, only 2 were infected, meaning 99.9% remained HIV-free. Lenacapavir also outperformed the daily oral regimen of emtricitabine/tenofovir (FTC/TDF). Based on these positive results, the trial’s blinded phase was ended early, and all participants will now have access to open-label Lenacapavir. Gilead aims to submit regulatory filings worldwide by the end of 2024, potentially bringing the first twice-yearly HIV prevention option to market by 2025.Key Data from the PURPOSE 2 Trial
PURPOSE 2 is a Phase III, double-blind, multicenter, randomized study comparing the safety and efficacy of Lenacapavir administered as a subcutaneous injection every six months to daily oral FTC/TDF for pre-exposure prophylaxis (PrEP). The study included over 3,200 participants—cisgender men, transgender men, transgender women, and non-binary individuals—aged 16 and older across 88 trial centers in Argentina, Brazil, Mexico, Peru, South Africa, Thailand, and the United States. Participants were randomly assigned in a 2:1 ratio to either the Lenacapavir or FTC/TDF group.
Key findings include:
- In the Lenacapavir group (2,180 participants), only 2 HIV infections occurred, representing an incidence rate of 0.10 per 100 person-years; 99.9% of participants remained HIV-free.
- Compared to the background HIV infection rate (2.37 per 100 person-years), Lenacapavir showed a 96% relative risk reduction (incidence rate ratio = 0.04, P < 0.0001).
- In the FTC/TDF group (1,087 participants), 9 infections occurred, with an incidence rate of 0.93 per 100 person-years.
- Lenacapavir demonstrated 89% greater efficacy in preventing HIV infection compared to FTC/TDF (incidence rate ratio = 0.11, P = 0.00245).
- Both Lenacapavir and FTC/TDF were well tolerated, with no significant or new safety concerns reported.
Following the impressive results from the PURPOSE 1 trial earlier this year, which recorded zero infections in adolescent and young women, the positive interim results of PURPOSE 2 further strengthen Lenacapavir’s potential as a long-acting HIV prevention solution. With these strong data, Gilead plans to submit regulatory filings by the end of 2024, positioning Lenacapavir as a new option in the PrEP landscape by 2025.
