Gilead's Lenacapavir Reduces HIV Infections by 96%, Surpassing Truvada in Twice-Yearly PrEP Treatment

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Data from the Phase III PURPOSE 2 trial demonstrated that Gilead’s lenacapavir reduced HIV infections by 96% compared to background HIV incidence (bHIV). According to the company, the trial also demonstrated lenacapavir's superiority over once-daily Truvada (F/TDF) when administered twice-yearly. An independent Data Monitoring Committee recommended early unblinding of the trial due to these results, allowing open-label access for all participants.¹

“With such remarkable outcomes across two Phase III studies, lenacapavir has demonstrated the potential to transform the prevention of HIV and help to end the epidemic,” said Daniel O’Day, chairman, CEO, Gilead, in a press release. “Now that we have a comprehensive dataset across multiple study populations, Gilead will work urgently with regulatory, government, public health and community partners to ensure that, if approved, we can deliver twice-yearly lenacapavir for (preexposure prohylaxis [PrEP]) worldwide, for all those who want or need PrEP.”

The double-blind, multicenter, randomized PURPOSE 2 study evaluated the safety and efficacy of twice-yearly subcutaneous lenacapavir for PrEP compared to once-daily oral Truvada and bHIV in over 3,200 cisgender men, transgender men, transgender women, and gender non-binary patients over the age of 16 years who are sexually active with people assigned male at birth. As part of the study, there were 88 trial sites across Argentina, Brazil, Mexico, Peru, South Africa, Thailand, and the United States. Patients were randomly assigned in a 2:1 ratio to receive either lenacapaviror Truvada. The primary endpoint of the study was superiority of lenacapavir over Truvda.

In addition to lenacapavir producing a 96% reduction in HIV infections compared to bHIV, there were only two reported cases among 2,180 participants, which equals an HIV-free rate of 99.9%. Additionally, the trial found that lenacapavir demonstrated 89% greater efficacy over treatment with once-daily Truvada. According to Gilead, these results complement earlier findings from the PURPOSE 1 trial in cisgender women in sub-Saharan Africa.¹

Serious adverse events (AEs) of lenacapavir include dark urine, fever, inability to move the arms and legs, joint pain, skin rash, nausea and vomiting, muscle tenderness, tiredness, weight loss, and yellow eyes or skin. The most commonly reported AEs were nausea and injection site reactions.²

“The difficulty some people can experience with taking an oral pill every day, including challenges with adherence and stigma, have hindered uptake and persistence of the standard of care for too long, thus blunting PrEP’s impact on HIV prevention,” said PURPOSE 2 principal investigator Onyema Ogbuagu, MBBCh, FACP, FIDSA, associate professor, medicine and pharmacology, Yale School of Medicine, director, Yale Antivirals and Vaccines Research Program, in the press release. “The incredible efficacy demonstrated in the PURPOSE 2 trial, the potential benefits of a twice-yearly injection, and the diversity of trial sites and participants show the impact that lenacapavir for PrEP could have for people around the world who need new choices to reduce their chances of acquiring HIV. This breakthrough adds significantly to our arsenal of tools to move us closer to achieving an AIDS-free generation.”

Gilead plans to submit global regulatory filings by the end of the year, with the goal of making lenacapavir accessible, particularly in high-incidence, low-resource areas. The company stated that it has the potential to become the first twice-yearly HIV prevention therapy as early as next year.¹

“In the United States, the stubbornly high rate of HIV diagnoses—especially in the U.S. South, and particularly among gay and bisexual men of color and transgender people—demands novel approaches to help people prevent HIV acquisition,” said Colleen Kelley, MD, MPH, professor of medicine, Emory University, PURPOSE 2 principal investigator, in the press release. “Because adherence to oral products can be challenging for some people, twice-yearly injectable lenacapavir for PrEP has the potential to be one of the most impactful interventions we could have to drive down new infections and bring us closer to ending the HIV epidemic in the United States.”

References

Gilead’s Twice-Yearly Lenacapavir for HIV Prevention Reduced HIV Infections by 96% and Demonstrated Superiority to Daily Truvada® in Second Pivotal Phase 3 Trial. Gilead. September 12, 2024. Accessed September 13, 2024. https://www.gilead.com/news-and-press/press-room/press-releases/2024/9/gileads-twiceyearly-lenacapavir-for-hiv-prevention-reduced-hiv-infections-by-96-and-demonstrated-superiority-to-daily-truvada-in-second-pivotal-ph 

2. Lenacapavir Side Effects. Drugs.com. Accessed September 13, 2024. https://www.drugs.com/sfx/lenacapavir-side-effects.html