Gilead's Biannual Lenacapavir Shows 100% Efficacy, Superior to Daily Truvada for HIV Prevention

Gilead Sciences, Inc. has disclosed the results of an interim analysis from its pivotal Phase 3 PURPOSE 1 trial. The trial revealed that the company’s twice-yearly injectable HIV-1 capsid inhibitor, lenacapavir, achieved 100% efficacy in preventing HIV infections among cisgender women. Given these promising outcomes, the independent Data Monitoring Committee (DMC) has advised Gilead to terminate the trial's blinded phase and provide open-label lenacapavir to all participants.

Dr. Merdad Parsey, Chief Medical Officer at Gilead Sciences, emphasized the potential impact of twice-yearly lenacapavir on HIV prevention, stating, "With zero infections and 100% efficacy, twice-yearly lenacapavir has demonstrated its potential as an important new tool to help prevent HIV infections." He also indicated an eagerness to see additional results from the ongoing PURPOSE clinical program.

The PURPOSE program is characterized as the most comprehensive and diverse HIV prevention trial ever conducted. It includes five trials concentrated on scientific innovation, trial design, community engagement, and health equity. PURPOSE 1, a Phase 3, double-blind, randomized study, assesses the safety and efficacy of twice-yearly lenacapavir for pre-exposure prophylaxis (PrEP) and once-daily oral Descovy (emtricitabine 200mg and tenofovir alafenamide 25mg; F/TAF). The study involves over 5,300 cisgender women and adolescent girls aged 16-25 across 28 sites in South Africa and Uganda.

Participants were divided into three groups, with one receiving twice-yearly lenacapavir, another taking once-daily oral Descovy, and a third group taking once-daily oral Truvada. There was no placebo group, as effective PrEP options already exist, making a placebo group unethical. Instead, background HIV incidence (bHIV) and Truvada were used as comparators.

The interim analysis showed no HIV infections in the lenacapavir group, demonstrating its superiority over bHIV (2.41 per 100 person-years) and Truvada, with significant statistical results (p<0.0001). Lenacapavir was generally well-tolerated with no significant new safety concerns. In contrast, the efficacy of Descovy was similar to Truvada and did not show statistical superiority over bHIV. Both Descovy and Truvada were well-tolerated, and no new safety issues were identified.

Linda-Gail Bekker, Director of the Desmond Tutu HIV Center at the University of Cape Town, highlighted the potential of lenacapavir to provide a critical new choice for HIV prevention. She mentioned that twice-yearly lenacapavir could help address issues related to stigma and discrimination associated with daily oral PrEP pills and might improve adherence due to its dosing schedule.

It is important to note that the use of lenacapavir and Descovy for HIV prevention in cisgender women is still investigational and has not yet been approved.

Further trials within the PURPOSE program are ongoing. The next significant results are expected from PURPOSE 2, which tests twice-yearly lenacapavir for PrEP among cisgender men, transgender men, transgender women, and gender non-binary individuals in various countries including Argentina, Brazil, Mexico, and the U.S. The regulatory submission for lenacapavir for PrEP will incorporate results from both PURPOSE 1 and 2, aiming to secure approval for diverse populations in need of additional HIV prevention options.

Gilead remains committed to partnering with communities heavily impacted by HIV. Community input has been vital in shaping the PURPOSE trials, ensuring rigorous, innovative, and inclusive approaches to HIV prevention research. Gilead also plans to brief community partners and offer a public statement on its access strategy for lenacapavir in high-incidence, resource-limited countries, primarily low and lower-middle-income regions.

In summary, Gilead Sciences’ PURPOSE 1 trial has shown that twice-yearly injectable lenacapavir is highly effective in preventing HIV infections among cisgender women, potentially offering a new, impactful tool in the fight against HIV. Further results from ongoing trials are awaited to confirm these findings and expand their applicability to broader populations.