Gilead Sciences, Inc. (Nasdaq: GILD) announced outstanding results from its pivotal Phase 3 PURPOSE 1 trial, which assessed the efficacy and safety of lenacapavir, a twice-yearly injectable HIV-1 capsid inhibitor. The study demonstrated that lenacapavir achieved zero infections and 100% efficacy compared to background HIV incidence and daily Truvada® (emtricitabine 200mg and tenofovir disoproxil fumarate 300mg; F/TDF) for pre-exposure prophylaxis (PrEP) in cisgender women. This significant milestone suggests that lenacapavir could become the first and only twice-yearly PrEP option, addressing critical gaps in uptake and adherence among individuals who need or want PrEP.
The new data provide a comprehensive look at the efficacy, safety, and tolerability of twice-yearly lenacapavir injections. The PURPOSE 1 trial’s interim analysis revealed zero HIV infections in the lenacapavir group, translating to a 100% reduction in HIV infections. Additionally, lenacapavir showed superior prevention of HIV infections when compared to daily oral Truvada. Following a single 3e13 vg/kg dose, lenacapavir demonstrated a statistically significant reduction in mean total annualized bleeding rate (ABR) compared to the pre-infusion period (1.24 vs. 4.73; one-sided p-value=0.0040). Key secondary endpoints were also met, with 84% of participants maintaining FVIII activity above 5% at 15 months post-infusion (one-sided p-value = 0.0086).
Adherence and Demographics
Adherence to lenacapavir was notably high, with 91.5% of trial participants receiving on-time injections at week 26, and 92.8% at one year. In contrast, adherence to daily oral Descovy and Truvada was low and declined over time. Among the Descovy group, those with medium or high adherence had significantly lower odds of acquiring HIV compared to those with low adherence (odds ratio 0.11; 95% CI, 0.012 to 0.49; p=0.0006). The trial included diverse demographics, with 5,345 HIV-negative cisgender adolescent girls and young women aged 16-26 from South Africa and Uganda participating.
Lenacapavir was generally well tolerated, with transient elevated FVIII levels observed in 49.3% of dosed participants, but without impacting efficacy and safety. Serious adverse events were reported in 20% of patients, but treatment-related adverse events resolved with clinical management. Common adverse events included headache, urinary tract infection, and genitourinary chlamydia infection, but no serious injection site reactions were noted. The trial’s rigorous design and community-focused approach have set new standards for person-centered HIV prevention trials.
Addressing Global HIV Incidence
Gilead is committed to ensuring that the groundbreaking data from PURPOSE 1 translate into decreased HIV incidence globally. An access strategy is being developed to prioritize the regulatory approval of twice-yearly lenacapavir for PrEP in high-incidence, resource-limited countries. Gilead plans to discuss the data with regulatory authorities to facilitate swift approval and access.
Gilead expects results from the PURPOSE 2 trial, which assesses lenacapavir for PrEP among cisgender men, transgender men, transgender women, and gender non-binary individuals, by late 2024 or early 2025. The regulatory filing for lenacapavir for PrEP will include results from both PURPOSE 1 and PURPOSE 2, ensuring broad approval for multiple populations and communities in need of additional HIV prevention options.
Gilead’s Commitment to HIV Research
For over 35 years, Gilead has been at the forefront of HIV research, developing 12 HIV medications and pioneering treatments like the first single-tablet regimen for HIV and the first long-acting injectable HIV treatment. Gilead’s continuous innovation aims to transform HIV into a treatable, preventable, chronic condition. Through collaborations and partnerships, Gilead strives to improve education, expand access, and address barriers to care, with the goal of ending the HIV epidemic globally.
Gilead’s PURPOSE program is the most comprehensive and diverse HIV prevention trial program ever conducted. It comprises five trials focused on scientific innovation, community engagement, and health equity. The program evaluates lenacapavir’s safety and efficacy as a long-acting PrEP option for diverse populations.
The positive Phase 3 results for lenacapavir underscore its potential as a groundbreaking HIV prevention therapy. With high efficacy, superior adherence, and a well-tolerated safety profile, lenacapavir represents a significant advancement in reducing the global HIV burden. Gilead’s commitment to rapid access and regulatory approval highlights its dedication to addressing critical gaps in HIV prevention and improving health outcomes worldwide.
Resource: Gilead, July 24, 2024
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