Phase III Trial Data Demonstrates Efficacy of Lenacapavir in Preventing HIV in Cisgender Women

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Results from the Phase III PURPOSE 1 trial evaluating lenacapavir as a twice-yearly injectable HIV-1 capsid inhibitor for HIV prevention demonstrated a 100% efficacy rate in preventing HIV infections in cisgender women. The data, published in The New England Journal of Medicine and presented at 25th International AIDS Conference (AIDS 2024) in Munich, Germany, found that lenacapavir was superior to both Descovy and Truvada in preventing HIV. According to the company, the trial is considered to be groundbreaking due to its inclusion of pregnant women and adolescents.¹

“These stellar results show that twice-yearly lenacapavir for (preexposure prophylaxis [PrEP]), if approved, could offer a highly effective, tolerable and discreet choice that could potentially improve PrEP uptake and persistence, helping us to reduce HIV in cisgender women globally,” said Linda-Gail Bekker, MBChB, DTM&H, DCH, FCP(SA), PhD, director, Desmond Tutu HIV Center, University of Cape Town, South Africa, former president, International AIDS Society, in a press release. “PURPOSE 1 also sets a new standard for person-centered HIV prevention trials, demonstrating what can happen when a thoughtful scientific and community-focused trial design, a promising drug candidate and an inclusive trial implementation plan come together.”

PURPOSE 1 is a double-blind, active-controlled, multicenter, randomized trial that collected data from 5,345 HIV-negative, cisgender adolescent girls and young women aged 16-26 years at 25 sites in South Africa and three sites in Uganda. Gilead stated that lenacapavir and Descovy were tested in parallel for HIV prevention, with one group receiving twice-yearly injectable lenacapavir, one group taking once-daily oral Descovy, and a third group taking once-daily oral Truvada. The primary endpoint of the study was superiority of twice-yearly lenacapavir to background HIV incidence and once-daily oral Truvada

Results found that injection with lenacapavir showed high adherence rates, with 91.5% on-time injections at 26 weeks and 92.8% at one year; however, adherence to Descovy and Truvada was low and declined as time went on. Additionally, 30.2% of participants in the Descovy group had high or medium adherence to the drug at 26 weeks, with 69.8% having low adherence. After a year, this decreased to 15.9%, while low adherence increased to 84.1%. For Truvada at 26 weeks, 10.9% of trial participants had high or medium adherence, and 89.1% had low adherence. After a year, 7.0% of trial participants had high or medium adherence and 93.0% had low adherence.

Both lenacapavir and Descovy were well tolerated, with no new safety signals identified. Common adverse events (AEs) included headache, urinary tract infection, genitourinary chlamydia infection, and nausea. In the lenacapavir group, serious AEs were reported in 2.8% of patients, 4% in the Descovy group, and 3.3% in the Truvada group. While there were no serious injection site reactions (ISRs), ISRs related to the study drug or injection procedures were the most common AEs observed.¹

“As the most comprehensive and diverse HIV prevention trial program ever conducted, the PURPOSE program embodies both the scientific and person-centered innovations that Gilead believes are critical to help end the HIV epidemic for everyone, everywhere,” said Jared Baeten, MD, PhD, SVP, clinical development, HIV franchise head, Gilead Sciences, in a press release. “As the only twice-yearly choice for HIV prevention, lenacapavir for PrEP could provide a critical new option for people who need or want PrEP around the world.”

Currently, the use of lenacapavir and Descovy for the prevention of HIV in cisgender women is investigational and have not yet been approved anywhere globally.¹

Reference

Full Efficacy and Safety Results for Gilead Investigational Twice-Yearly Lenacapavir for HIV Prevention Presented at AIDS 2024. Gilead. July 24, 2024. Accessed July 24, 2024. https://www.gilead.com/news-and-press/press-room/press-releases/2024/7/full-efficacy-and-safety-results-for-gilead-investigational-twice-yearly-lenacapavir-for-hiv-prevention-presented-at-aids-2024