Gilead announces PURPOSE 2 met efficacy endpoints, reduced HIV infections by 96%

Gilead announced the results of an interim analysis from a second pivotal Phase 3 clinical trial investigating the use of the company’s twice-yearly injectable HIV-1 capsid inhibitor, lenacapavir. Lenacapavir reduced HIV infections by 96% compared to background HIV incidence, or bHIV. There were two incident cases among 2,180 participants, corresponding to 99.9% of participants not acquiring HIV infection in the lenacapavir group. Twice-yearly lenacapavir also demonstrated superiority to once-daily Truvada. The trial, PURPOSE 2, includes cisgender men, transgender men, transgender women, and gender non-binary individuals in Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the United States who have sex with partners assigned male at birth. At interim analysis, the independent Data Monitoring Committee, or DMC, confirmed that the PURPOSE 2 trial met its key efficacy endpoints of superiority of twice-yearly lenacapavir to both bHIV and once-daily oral Truvada for pre-exposure prophylaxis, or PrEP. Therefore, the DMC recommended that Gilead stop the blinded phase of the trial and offer open-label lenacapavir to all participants. This is the second pivotal Phase 3 trial to demonstrate superior efficacy for twice-yearly lenacapavir for the investigational use of HIV prevention as PrEP. In June 2024, the PURPOSE 1 trial, studying lenacapavir for PrEP among cisgender women in sub-Saharan Africa, was also unblinded early because it met its key efficacy endpoints. The data from the PURPOSE 1 and PURPOSE 2 trials will support upcoming regulatory filings so that twice-yearly lenacapavir for PrEP, if approved, can be made available to multiple populations and communities around the world who are most in need of additional HIV prevention choices. Updates on regulatory filings for lenacapavir for PrEP will be shared as discussions with regulatory bodies progress. Gilead will begin a series of global regulatory filings by the end of 2024. This could support the initial launch of the first and only twice-yearly HIV prevention choice in 2025. Gilead is executing an access strategy that prioritizes speed and enables the most efficient paths for the regulatory review and approval of lenacapavir for PrEP in regions around the world. This strategy will prioritize high-incidence, low-resource countries, which are primarily low- and lower-middle income countries. Gilead is committed to making lenacapavir available in the countries where the need is greatest, including expediting voluntary licensing partners to supply high-quality, low-cost versions of lenacapavir. Gilead is actively working to finalize these contracts. PURPOSE 2, a phase 3, double-blind, multicenter, randomized study, is evaluating the safety and efficacy of twice-yearly subcutaneous lenacapavir for PrEP versus once-daily oral Truvada and background HIV incidence in more than 3,200 cisgender men, transgender men, transgender women and gender non-binary individuals aged 16 years or older who have sex with partners assigned male at birth. There were 88 trial sites in Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the United States. Study participants were randomized in a 2:1 ratio to lenacapavir and Truvada, respectively. Because effective PrEP options already exist, there is broad consensus in the PrEP field that a placebo group would be unethical; thus, the trial used bHIV as the primary comparator and Truvada as a secondary comparator. There were 2 incident cases among 2,180 participants in the lenacapavir group; 99.9% of participants did not acquire HIV in the lenacapavir group. The results demonstrated superiority of twice-yearly lenacapavir over bHIV, with 96% relative risk reduction. There were nine incident cases among 1,087 individuals in the Truvada group. Twice-yearly lenacapavir was 89% more effective than once-daily Truvada. In the trial, lenacapavir and Truvada were generally well-tolerated and no significant or new safety concerns were identified. More detailed data from PURPOSE 2 will be presented at a future conference.