Gilead Sciences, Inc. announced topline results from an interim analysis of its pivotal Phase 3 PURPOSE 1 trial, demonstrating that the company’s twice-yearly injectable HIV-1 capsid inhibitor, lenacapavir, achieved 100% efficacy for the investigational use of HIV prevention in cisgender women.

The PURPOSE 1 trial met its key efficacy endpoints, showing the superiority of twice-yearly lenacapavir over 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) has recommended halting the blinded phase of the trial to offer open-label lenacapavir to all participants.

“With zero infections and 100% efficacy, twice-yearly lenacapavir has demonstrated its potential as an important new tool to help prevent HIV infections,” said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. “We look forward to additional results from the ongoing PURPOSE clinical program and continuing toward our goal of helping to end the HIV epidemic for everyone, everywhere.”

The PURPOSE 1 trial is part of Gilead’s comprehensive and diverse PURPOSE program, the most extensive HIV prevention trial program ever conducted. It includes five global trials 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 over 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 another group taking once-daily oral Descovy. Additionally, a third group was assigned to once-daily oral Truvada. Study participants were randomized in a 2:2:1 ratio to lenacapavir, Descovy, and Truvada, respectively. Due to the effectiveness of existing PrEP options, the trial used bHIV as the primary comparator and Truvada as a secondary comparator.

There were zero incident cases of HIV infection among women in the lenacapavir group (incidence 0.00 per 100 person-years). The results demonstrated the superiority of twice-yearly lenacapavir over bHIV (primary endpoint, incidence 2.41 per 100 person-years) and over once-daily Truvada (secondary endpoint), with p<0.0001 for both endpoints. Lenacapavir was generally well-tolerated with no significant or new safety concerns identified.

HIV incidence in the Descovy group was numerically similar to that in the Truvada group and was not statistically superior to bHIV. Adherence analyses for Descovy and Truvada are ongoing, given the challenges with adherence to daily oral pills for PrEP. Both Descovy and Truvada were generally well-tolerated with no new safety concerns identified.

Detailed data from PURPOSE 1 will be presented at a future conference.

“Twice-yearly lenacapavir for PrEP, if approved, could provide a critical new choice for HIV prevention that fits into the lives of many people who could benefit from PrEP around the world—especially cisgender women,” said Linda-Gail Bekker, MBChB, DTM&H, DCH, FCP(SA), PhD, Director of the Desmond Tutu HIV Center at the University of Cape Town, South Africa, and past President of the International AIDS Society. “While traditional HIV prevention options are highly effective when taken as prescribed, twice-yearly lenacapavir for PrEP could help address the stigma and discrimination some people face when taking or storing oral PrEP pills, as well as potentially increase PrEP adherence and persistence given its twice-yearly dosing schedule.”

The use of lenacapavir and Descovy for the prevention of HIV in cisgender women are investigational and have not been determined to be safe or efficacious and are not approved anywhere globally.

Additional PURPOSE Trials Assessing Twice-Yearly Lenacapavir for PrEP

Gilead expects results in late 2024/early 2025 from the program’s other pivotal trial, PURPOSE 2, which assesses 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, 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 disproportionately affected by HIV in their respective countries and regions. Community input on the PURPOSE trials has been instrumental in factors ranging from program design to participant recruitment strategies. This collaborative approach will continue to help Gilead implement clinical trials with rigor, innovation, and intentional inclusion of communities historically underrepresented in HIV prevention research. It will also bolster post-implementation science activities for PURPOSE 1 and future successful trials.

Gilead recognizes the importance of enabling access 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, primarily low- and lower-middle-income countries.