Phase III Trial Data Show Lenacapavir Demonstrated 100% Efficacy Preventing HIV in Cisgender Women

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Gilead Sciences announced encouraging interim results from its Phase III PURPOSE 1 trial evaluating the efficacy of the twice-yearly injectable HIV-1 capsid inhibitor, lenacapavir, for HIV prevention in cisgender women. According to the company, results found that lenacapavir demonstrated an efficacy rate of 100%, making it superior to once-daily oral Truvada (emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg). As a result, an independent Data Monitoring Committee suggested that Gilead should end the blinded phase of the trial and begin administering pen-label lenacapavir to all participants.¹

“With zero infections and 100% efficacy, twice-yearly lenacapavir has demonstrated its potential as an important new tool to help prevent HIV infections,” said Merdad Parsey, MD, PhD, chief medical officer, Gilead Sciences, in a press release. “We look forward to additional results from the ongoing PURPOSE clinical program and continuing toward our goal of helping to end the HIV epidemic for everyone, everywhere.”

The double-blind, randomized PURPOSE 1 trial is evaluating the safety and efficacy of twice-yearly, subcutaneous lenacapavir for pre-exposure prophylaxis (PrEP) and once-daily oral Descovy (emtricitabine 200 mg and tenofovir alafenamide 25 mg). Over 5,300 cisgender women and adolescent girls between the ages of 16-25 years across South Africa and Uganda were recruited, with one group receiving twice-yearly lenacapavir and the other taking once-daily oral Descovy. A third group was given once-daily oral Truvada. The primary endpoint of the study was superiority of twice-yearly lenacapavir over background HIV incidence (bHIV), with the secondary endpoint being superiority over Truvada.

Results found that in the lenacapavir group, zero HIV infections were reported among 2,134 women. In the Truvada group, there was a reported 16 cases out of 1,068 women. In the Descovy group, there were 39 cases reported out of 2,136 women, which was not superior to bHIV. The results suggested that lenacapavir has the potential to improve adherence and reduce stigma associated with daily oral PrEP regimens, according to the investigators. More data from the trial are expected to be announced at a later date.

Lenacapavir, Descovy, and Truvada were all generally well-tolerated, with no new safety signals reported from the trial. Common adverse events in the Descovy cohort included diarrhea, nausea, headache, fatigue, and abdominal pain.

Results from PURPOSE 2—which is evaluating different populations including cisgender men and transgender individuals from Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the United States—are expected later this year or in early 2025. The trials are also expected to support regulatory filings to expand lenacapavir's approval across diverse populations.¹

“Twice-yearly lenacapavir for PrEP, if approved, could provide a critical new choice for HIV prevention that fits into the lives of many people who could benefit from PrEP around the world—especially cisgender women,” said Linda-Gail Bekker, MBChB, DTM&H, DCH, FCP(SA), PhD, director, Desmond Tutu HIV Center at the University of Cape Town, South Africa, past president, International AIDS Society, in the press release. “While we know traditional HIV prevention options are highly effective when taken as prescribed, twice-yearly lenacapavir for PrEP could help address the stigma and discrimination some people may face when taking or storing oral PrEP pills, as well as potentially help increase PrEP adherence and persistence given its twice-yearly dosing schedule.”

Currently, neither lenacapavir nor Descovy have been approved for the prevention of HIV in cisgender women by any regulatory body globally.¹

Reference

1. Gilead’s Twice-Yearly Lenacapavir Demonstrated 100% Efficacy and Superiority to Daily Truvada® for HIV Prevention. Gilead. June 20, 2024. Accessed June 21, 2024. https://www.gilead.com/news-and-press/press-room/press-releases/2024/6/gileads-twiceyearly-lenacapavir-demonstrated-100-efficacy-and-superiority-to-daily-truvada-for-hiv-prevention