FDA approves twice-yearly lenacapavir as PrEP for HIV in adolescents, adults

FDA approves lenacapavir as PrEP for HIV in adults, adolescents weighing at least 35 kg | Image Credit: Contemporary Pediatrics

On June 18, 2025, the FDA approved Gilead Sciences' lenacapavir (Yeztugo), an injectable HIV-1 capsid inhibitor, indicated as pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV in adults and adolescents who weigh at least 35 kg (77.16 lbs), according to a press release from the company.¹

With the federal agency's decision, lenacapavir becomes the first and only twice-yearly option available in the United States for those who need or want PrEP, stated Gilead.

Approval for lenacapavir's new drug application (NDA) was supported by data from the phase 3 PURPOSE 1 (NCT04994509) and PURPOSE 2 (NCT04925752) clinical trials. In PURPOSE 1, the primary analysis demonstrated that twice-yearly subcutaneous lenacapavir resulted in 0 HIV infections among 2134 participants in the lenacapavir group. Additionally, lenacapavir demonstrated "superiority of prevention of HIV infections when compared with once-daily oral Truvada (emtricitabine 200mg and tenofovir disoproxil fumarate 300mg; F/TDF) in cisgender women in sub-Saharan Africa," according to Gilead.

In PURPOSE 2, data demonstrated 2 HIV infections from a group of 2179 participants in the lenacapavir group, demonstrating 99.9% of participants in the lenacapavir group did not acquire HIV infection. Superiority was observed for the prevention of HIV infections compared to once-daily emtricitabine 200mg and tenofovir disoproxil fumarate 300mg; F/TDF in a "broad and geographically diverse range of cisgender men and gender-diverse people," stated Gilead.

Data revealed that more than 99.9% of study participants who received lenacapavir in both trials remained HIV negative.

"[Lenacapavir] could be the transformative PrEP option we’ve been waiting for—offering the potential to boost PrEP uptake and persistence and adding a powerful new tool in our mission to end the HIV epidemic,” said Carlos del Rio, MD, in a statement. Del Rio is a distinguished professor of medicine in the Division of Infectious Diseases at Emory University School of Medicine and co-director of the Emory Center for AIDS Research in Atlanta, Georgia.

"A twice-yearly injection could greatly address key barriers like adherence and stigma, which individuals on more frequent PrEP dosing regimens, especially daily oral PrEP, can face," added del Rio. "We also know that, in research, many people who need or want PrEP preferred less frequent dosing.”

According to the World Health Organization, there were an estimated 39.9 million people living with HIV at the end of 2023, of which 1.4 million were aged 0 to 14 years, with the rest being aged 15 years or older. The same year, 1.3 million people acquired HIV. Since 2010, the number of people acquiring HIV decreased by 39% from 2.1 million.²

"This is a historic day in the decades-long fight against HIV," said Daniel O'Day, chairman and CEO, Gilead Sciences, in the press release. "This is a medicine that only needs to be given twice a year and has shown remarkable outcomes in clinical studies, which means it could transform HIV prevention. Gilead scientists have made it their life’s work to end HIV and now, with the FDA approval of Yeztugo and in collaboration with our many partners, we can help to make that goal a reality.”

Reference:

1. Yeztugo (lenacapavir) is now the first and only FDA-approved HIV prevention option offering 6 months of protection. Gilead. Press release. June 18, 2025. Accessed June 18, 2025. https://www.gilead.com/news/news-details/2025/yeztugo-lenacapavir-is-now-the-first-and-only-fda-approved-hiv-prevention-option-offering-6-months-of-protection
2. Global HIV Programme. World Health Organization. Accessed June 18, 2025. https://www.who.int/teams/global-hiv-hepatitis-and-stis-programmes/hiv/strategic-information/hiv-data-and-statistics