Gilead Shares Complete PURPOSE 2 Results for Biannual Lenacapavir in HIV Prevention at HIV Glasgow

Gilead Sciences, Inc. (Nasdaq: GILD) has presented comprehensive data from its Phase 3 PURPOSE 2 trial (NCT04925752), which evaluates the use of twice-yearly injectable lenacapavir, an HIV-1 capsid inhibitor, for HIV prevention among cisgender men and gender-diverse individuals. The findings, discussed at the International Congress on Drug Therapy in HIV Infection (HIV Glasgow), will also be published in The New England Journal of Medicine.

The trial's complete data release follows the unblinding at interim analysis in September and earlier presentations at the HIV Research for Prevention Conference in Lima, Peru. Previously shared data illustrated that lenacapavir reduced HIV infections by 96% compared to background HIV incidence, with only two incident cases among 2,179 participants, indicating that 99.9% of participants in the lenacapavir group did not acquire HIV. Lenacapavir also demonstrated superior efficacy to once-daily Truvada® (emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg; F/TDF) for pre-exposure prophylaxis (PrEP) and was generally well-tolerated without significant new safety concerns.

Dr. Onyema Ogbuagu, the Principal Investigator of PURPOSE 2 and an Associate Professor at Yale School of Medicine, emphasized the transformative potential of a twice-yearly HIV prevention option. He noted that lenacapavir could address various unmet needs for individuals requiring or opting for PrEP worldwide.

Participants in the trial exhibited high adherence to lenacapavir and placebo injections, with 91.0% receiving on-time injections at week 26 and 92.8% at one year. The on-time injection rates remained consistent across both study groups. Lenacapavir proved highly effective in reducing HIV infections, with only two cases among 2,179 participants despite high levels of sexual behavior and sexually transmitted infections reported among participants. The trial data confirmed that both individuals who acquired HIV did so after their first lenacapavir injection but before their second, diagnosed through standard HIV tests without delayed diagnosis.

Conversely, adherence to Truvada declined over time. Initial adherence, measured through the detection of tenofovir diphosphate in blood samples, was high at 82% at week 8 but dropped to 67% at week 26 and 62% at one year. In the Truvada group, there were nine incident HIV cases among 1,086 participants, all linked to low or no adherence or discontinuation of the medication.

The PURPOSE 2 trial is a Phase 3, double-blind, multicenter, randomized study assessing the safety and efficacy of twice-yearly subcutaneous lenacapavir for PrEP compared to background HIV incidence and once-daily Truvada. The trial included 3,271 cisgender gay and bisexual men, transgender women, and gender non-binary individuals aged 16 years or older who have sex with partners assigned male at birth, across 88 sites in Argentina, Brazil, Mexico, Peru, South Africa, Thailand, and the United States. Participants were randomized in a 2:1 ratio to lenacapavir and Truvada.

The PURPOSE 2 trial is the second pivotal Phase 3 trial demonstrating the superior efficacy of twice-yearly lenacapavir for HIV prevention and was unblinded early after meeting its key efficacy endpoints. The PURPOSE 1 trial, studying lenacapavir for PrEP among cisgender women in sub-Saharan Africa, was also unblinded early for similar reasons.

Gilead continues to focus on global access strategies for lenacapavir, including regulatory filings that will begin by the end of 2024. The FDA has granted lenacapavir for PrEP Breakthrough Therapy Designation and a rolling review to expedite the drug's application process. Additionally, Gilead has signed licensing agreements with six pharmaceutical companies to manufacture and supply cost-effective versions of lenacapavir for 120 resource-limited countries. The company is working on additional access strategies for middle and high-income countries to ensure efficient regulatory reviews and support for those needing PrEP.

Gilead emphasizes the importance of HIV prevention and is committed to ensuring broad global access to lenacapavir for PrEP, pending approval. The company plans to update on regulatory filings for lenacapavir for PrEP as discussions with regulatory bodies progress.