Full Results for Gilead's Twice-Yearly Lenacapavir for HIV Prevention Unveiled at AIDS 2024

Gilead Sciences, Inc. has unveiled comprehensive efficacy and safety outcomes from its Phase 3 PURPOSE 1 trial, focusing on the HIV-1 capsid inhibitor lenacapavir. Lenacapavir, administered as a bi-annual injection, has exhibited remarkable efficacy in preventing HIV infections among cisgender women, showing zero infections and 100% efficacy in the trial's interim results. These findings, demonstrating lenacapavir's superiority over traditional daily oral Truvada (emtricitabine and tenofovir disoproxil fumarate), were shared at the 25th International AIDS Conference in Munich and have been published in The New England Journal of Medicine.

The PURPOSE 1 trial assessed lenacapavir's efficacy, safety, and adherence, particularly noting the challenges of daily oral pre-exposure prophylaxis (PrEP) adherence. Trial participants included pregnant women and adolescents, ensuring a diverse and inclusive study demographic. Linda-Gail Bekker, Director of the Desmond Tutu HIV Center, emphasized that the trial's success could enhance PrEP uptake and persistence, significantly reducing HIV rates among cisgender women globally.

To translate these promising results into real-world impact, Gilead is developing a strategy to expedite regulatory approval and access to lenacapavir for PrEP, especially in countries with high HIV incidence. The trial's interim analysis confirmed lenacapavir's 100% efficacy, significantly outperforming background HIV incidence and daily Truvada. Consequently, the independent Data Monitoring Committee recommended transitioning all participants to open-label lenacapavir.

The PURPOSE 1 trial, comprising 5,345 HIV-negative cisgender women aged 16-26 from South Africa and Uganda, compared twice-yearly injectable lenacapavir, daily oral Descovy, and daily oral Truvada. Participants were randomized into three groups, with demographics balanced across the groups. Due to the ethical implications, the trial used background HIV incidence and Truvada as comparators rather than a placebo.

Adherence rates to lenacapavir injections were high, with 91.5% of participants receiving on-time injections at 26 weeks and 92.8% at one year. Conversely, adherence to daily oral Descovy and Truvada was notably lower, reflecting existing challenges with daily PrEP regimens. The trial's data indicated that higher adherence to Descovy was strongly associated with better HIV protection.

Safety profiles for lenacapavir, Descovy, and Truvada were comparable, with no new safety concerns arising. Injection site reactions were the most common adverse events for lenacapavir, but no serious reactions were observed. Lenacapavir's unique administration method involves subcutaneous injections forming a drug depot, which diminishes over time.

PURPOSE 1 also broke new ground by including pregnant and lactating women, thanks to advocacy from community groups in South Africa and Uganda. Among the 510 pregnancies reported, no HIV infections occurred in the lenacapavir group, further underscoring its efficacy.

Looking ahead, Gilead anticipates results from the PURPOSE 2 trial by late 2024 or early 2025. This trial extends the evaluation of lenacapavir for PrEP to include cisgender men, transgender men, transgender women, and gender non-binary individuals across several countries. The regulatory submission for lenacapavir for PrEP will incorporate findings from both PURPOSE 1 and PURPOSE 2, aiming for approval across diverse populations in need of HIV prevention options.

Jared Baeten, Senior Vice President at Gilead Sciences, highlighted the trial's significance, noting that lenacapavir's bi-annual regimen could provide a crucial new option for global HIV prevention. The continued development and potential regulatory approval of lenacapavir represent a significant step towards offering a broader range of HIV prevention methods, aiming to address the evolving needs of affected populations worldwide.