FDA Approves Lenacapavir as the First Twice-Yearly PrEP for HIV Prevention

The FDA has approved Gilead’s lenacapavir — now with the brand name Yeztugo — for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV in adults and adolescents. Yeztugo is the first twice-yearly option for PrEP.

Carlos del Rio, M.D.

“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. We also know that, in research, many people who need or want PrEP preferred less frequent dosing," Carlos del Rio, M.D., said in a news release. 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.

The approval is based on data from two phase 3 trials: PURPOSE 1 and PURPOSE 2. The PURPOSE 1 trial enrolled 2,134 participants in the Yeztugo group and achieved a 100% reduction in HIV infections and superiority in the prevention of HIV infections when compared with once-daily oral Truvada (emtricitabine and tenofovir disoproxil fumarate) in cisgender women in sub-Saharan Africa. Truvada is another Gilead medication used for PrEP.

In the PURPOSE 2 trial, there were two HIV infections among 2,179 participants in the Yeztugo group, demonstrating that 99.9% of participants in the Yeztugo group did not acquire HIV infection and the superiority of prevention of HIV infections when compared with once-daily oral Truvada among a broad and geographically diverse range of cisgender men and gender-diverse people.

In both trials, no significant or new safety concerns were identified. Data from both trials were published in The New England Journal of Medicine.

Approximately 1.2 million people in the United States have HIV, according to the 2022 Centers for Disease Control and Prevention (CDC).

Compared to the height of the HIV epidemic in the mid-1980s, annual infections have decreased by more than two-thirds. This includes a 12% reduction in cases from 2018 (36,200) to 2022 (31,800), likely driven by an increase in PrEP prescriptions, viral suppression and HIV testing. Other FDA-approved forms of PrEP include Truvada (emtricitabine/tenofovir disoproxil fumarate) and Descovy (emtricitabine/tenofovir alafenamide), which are options for daily PrEP, taken as a pill. Apretude (cabotegravir) is an injectable option given every two months.

Increasing access to PrEP is one of the key initiatives of Ending the HIV Epidemic in the U.S., which aims to reduce the number of new HIV infections by 90% by 2030. However, only 36% of people who would benefit from PrEP were accessing it, a CDC estimate shows. Barriers to access include stigma and affordability.

HIV experts and advocates have high hopes for Yeztugo but also have expressed concerns about its price and availability. “It has to make its way into people’s bodies, and it has to make its way into the right people’s bodies,” said Peter Ehrenkranz, M.D., M.P.H., deputy director, HIV, at the Gates Foundation, a major funder of HIV programs. Ehrenkranz said, though, if the people who would benefit from PrEP protection can be encouraged to get the injections, “you’ve basically got a vaccine for those folks.”

Yeztugo’s annual list price is set at $28,218 in the U.S., according to an email from Jessica Smith, M.A., a Gilead spokesperson. Smith said the price is consistent with the list price of other branded PrEP drugs. Smith also said the company has seen high insurance coverage for PrEP, and she asserted that the vast majority of consumers have zero-dollar copays for the PrEP version of Gilead’s Descovy (emtricitabine and tenofovir alafenamide).

Gilead’s international strategy includes voluntary licensing for generics and providing its product at no profit until generics are available in 120 high-need countries, Smith added. Gilead is also exploring “innovative access strategies” for middle-income countries and guaranteeing access to Yeztugo to study participants.

The twice-yearly formulation of lenacapavir is a “huge win,” said Jonathan Z. Li, M.D., an associate professor at Harvard Medical School, in an interview today. But he said Yeztugo was a stepping stone to the formulation of lenacapavir for PrEP that would require an injection just once a year. Gilead presented pharmacokinetic data from a Phase 1 trial of the annual shot at the 2025 Conference on Retroviruses and Opportunistic Infections meeting in March. The company said the results showed that the lenacapavir concentrations from two different formulations of a once-yearly injection exceeded the concentrations associated with HIV protection in the phase 3 trials that supported Yeztugo’s application for approval by the FDA.

Johnathan Z. Li, M.D.

“Once a year is akin to a vaccine,” Li said. “It’s like a vaccine dosing schedule. Twice a year can still be a little bit challenging for busy people.”