Gilead Sciences, Inc. announced topline results from an interim analysis of its pivotal, Phase 3 PURPOSE 1 trial indicating that the company?s twice-yearly injectable HIV-1 capsid inhibitor, lenacapavir, demonstrated 100% efficacy for the investigational use of HIV prevention in cisgender women. PURPOSE 1 met its key efficacy endpoints of superiority of twice-yearly lenacapavir to once-daily oral Truvada (emtricitabine 200mg and tenofovir disoproxil fumarate 300mg; F/TDF) and background HIV incidence (bHIV). Based on these results, the independent Data Monitoring Committee (DMC) recommended that Gilead stop the blinded phase of the trial and offer open-label lenacapavir to all participants. These are the first data generated from Gilead?s landmark PURPOSE program, which is the most comprehensive and diverse HIV prevention trial program ever conducted. The PURPOSE program comprises five HIV prevention trials around the world that are focused on innovation in science, trial design, community engagement and health equity. Topline PURPOSE 1 data PURPOSE 1, a Phase 3, double-blind, randomized study, is evaluating the safety and efficacy of twice-yearly, subcutaneous lenacapavir for pre-exposure prophylaxis (PrEP) and once-daily oral Descovy (emtricitabine 200mg and tenofovir alafenamide 25mg; F/TAF) in more than 5,300 cisgender women and adolescent girls aged 16-25 across 25 sites in South Africa and three sites in Uganda. The drugs are being tested in parallel, with one group receiving twice-yearly lenacapavir and one group taking once-daily oral Descovy. Additionally, a third group was assigned once-daily oral Truvada. Study participants were randomized in a 2:2:1 ratio to lenacapavir, Descovy 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 0 incident cases of HIV infection among women in the lenacapavir group (incidence 0.00 per 100 person-years). The results demonstrated superiority of twice-yearly lenacapavir over bHIV (primary endpoint, incidence 2.41 per 100 person-years) and superiority of twice-yearly lenacapavir over once-daily Truvada (secondary endpoint), with p<0.0001 for both endpoints. In the trial, lenacapavir was generally well-tolerated and no significant or new safety concerns were identified. HIV incidence in the Descovy group was numerically similar to that in the Truvada group and was not statistically superior to bHIV. Previous clinical trials among cisgender women have commonly found challenges with adherence to daily oral pills for PrEP, and adherence analyses for Descovy and Truvada from PURPOSE 1 are ongoing. In the trial, both Descovy and Truvada were generally well-tolerated and no new safety concerns were identified. Gilead expects results in late 2024/early 2025 from the program?s other pivotal trial, PURPOSE 2, which is assessing twice-yearly lenacapavir for PrEP among cisgender men who have sex with men, transgender men, transgender women and gender non-binary individuals who have sex with partners assigned male at birth in Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the United States. The regulatory filing for lenacapavir for PrEP will include the results of both PURPOSE 1 and PURPOSE 2, if positive, in order to ensure lenacapavir for PrEP can be approved for multiple populations and communities most in need of additional HIV prevention options. Gilead is committed to partnering with communities that are disproportionately affected by HIV in their respective countries and regions, and community input on the PURPOSE trials has been instrumental in factors ranging from program design to participant recruitment strategies. This kind of collaborative approach will continue to help Gilead implement clinical trials with rigor, innovation and intentional inclusion of communities that have historically been underrepresented in HIV prevention research. It will also help bolster the post-implementation science activities that Gilead will conduct for PURPOSE 1 and future successful trials.
Gilead recognizes the importance of helping to enable access in order for twice-yearly lenacapavir for PrEP, if approved by regulatory authorities, to achieve the broadest impact. In light of today?s milestone and the company?s ongoing commitment to communities affected by HIV, Gilead intends to brief community partners and provide a public statement regarding its planned access approach for high-incidence, resource-limited countries, which are primarily low- and lower-middle-income countries.