Full results from the Phase 3 PURPOSE 2 trial indicate that twice-yearly lenacapavir is highly effective in preventing HIV infection. The study, which included individuals aged 16 and older who have sex with male partners, demonstrated that lenacapavir met its primary efficacy endpoint of superiority to background HIV incidence and its key secondary endpoint of superiority to once-daily oral Truvada for PrEP. These findings, presented at the International Congress on Drug Therapy in HIV Infection and soon to be published in The New England Journal of Medicine, could transform HIV prevention strategies.
Strong Efficacy and Adherence
The PURPOSE 2 trial (NCT04925752) revealed that 99.9% of participants in the lenacapavir group did not acquire HIV, with only 2 incident cases among the 2180 patients. This translates to a 96% risk reduction compared to background HIV incidence. In contrast, the Truvada group had 9 incident cases among 1087 individuals, indicating that lenacapavir was 89% more effective. Notably, the study showed high adherence to lenacapavir, with 91% of participants receiving on-time injections at week 26 and 92.8% at one year. While Truvada adherence was initially high, it declined over time, with diphosphate levels consistent with high adherence seen in 82% of participants at week 8, 67% at week 26, and 62% at one year.
Study Design and Patient Population
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). The study cohort included 3295 participants from 88 sites across the world, including the US, Argentina, Thailand, Brazil, Mexico, Peru, and South Africa. The participants included cisgender men, transgender men, transgender women, and gender non-binary individuals aged 16 years or older.
Implications for HIV Prevention
"We’re at a crossroads in the HIV epidemic, and a twice-yearly choice for HIV prevention, if approved, could be transformative as we work toward achieving the UNAIDS 2030 targets around the world," said Onyema Ogbuagu, MBBCh, FACP, FIDSA, principal Investigator on the PURPOSE 2 trial. "Lenacapavir for PrEP could provide an important alternative to existing preventative medications that require more frequent dosing and could help transform the HIV prevention landscape by addressing a range of unmet needs for individuals who need or want PrEP globally."
Regulatory Pathway
Last month, the FDA granted PrEP Breakthrough Therapy Designation and rolling review to lenacapavir. Gilead plans to submit global regulatory filings for lenacapavir based on data from PURPOSE 1 (NCT04994509) and PURPOSE 2, starting by the end of 2024. "Gilead recognizes the importance of prevention in ending the HIV epidemic and is deeply committed to ensuring broad, sustainable global access to lenacapavir for PrEP, if approved," said Jared Baeten, MD, PhD, senior vice president of Clinical Development and Virology Therapeutic Area Head at Gilead Sciences.
