Gilead Sciences has announced that the U.S. Food and Drug Administration has accepted its supplemental New Drug Application for Yeztugo, a 300-mg lenacapavir tablet being studied as a once-weekly oral option for HIV prevention. If approved, it could become the first long-acting oral pre-exposure prophylaxis option for people who need or want HIV prevention beyond daily pills or injectable regimens.
The FDA has assigned a Prescription Drug User Fee Act action date of February 2, 2027. Gilead said the filing reflects its continued effort to expand HIV prevention choices and build on the established clinical profile of lenacapavir, which is already used in the Yeztugo regimen as an initial loading dose and as bridge therapy when twice-yearly injections are delayed.
The submission is supported by data from the PURPOSE 1 and PURPOSE 2 trials, which demonstrated high efficacy for lenacapavir in HIV prevention across diverse global populations. These studies included cisgender women, cisgender men, and gender-diverse people, supporting Gilead’s broader goal of developing HIV prevention options that respond to different needs, preferences, and real-life circumstances.
Once-weekly oral lenacapavir for PrEP remains investigational and is not approved anywhere globally. Gilead noted that Yeztugo injection is already approved in multiple countries as pre-exposure prophylaxis to reduce the risk of sexually acquired HIV in adults and adolescents at risk of HIV acquisition. Lenacapavir is also approved in several countries for the treatment of multi-drug-resistant HIV in adults when used with other antiretroviral medicines.
Lenacapavir works through a multi-stage mechanism of action that differs from other approved antiviral classes. While many antivirals act at a single stage of viral replication, lenacapavir is designed to inhibit HIV at multiple stages of its lifecycle. Gilead said the medicine has no known in vitro cross-resistance to other existing drug classes.
The company is continuing to evaluate lenacapavir in multiple ongoing and planned clinical studies for HIV prevention and treatment. Its research programme aims to develop long-acting oral and injectable options with different dosing frequencies, either alone or in combination, to better address the needs of people and communities affected by HIV.
The current U.S. indication for Yeztugo injection is for pre-exposure prophylaxis to reduce the risk of sexually acquired HIV-1 in adults and adolescents weighing at least 35 kg who are at risk of HIV-1 acquisition. Individuals must have a confirmed negative HIV-1 test before starting Yeztugo and before each subsequent injection.
Gilead also highlighted important safety information, including a boxed warning about the risk of drug resistance if Yeztugo is used by individuals with undiagnosed HIV-1 infection. The product is contraindicated in people with unknown or positive HIV-1 status, and individuals who acquire HIV while receiving Yeztugo must transition to a complete HIV treatment regimen.
The safety information also notes that Yeztugo should be used as part of a comprehensive HIV prevention strategy, including adherence to dosing schedules and safer sex practices to reduce the risk of sexually transmitted infections. Because Yeztugo has long-acting properties, residual concentrations may remain in the body for 12 months or longer after the last injection, making careful testing, follow-up, and prevention planning important.
The most common adverse reactions reported in Yeztugo clinical trials were injection site reactions, headache, and nausea. The product also has important drug interaction considerations, especially with certain CYP3A inducers, inhibitors, and medicines metabolized by CYP3A or P-gp.
Gilead said its work on Yeztugo is part of more than 35 years of HIV innovation. The company has developed multiple HIV medicines, including single-tablet treatment regimens, PrEP options, and long-acting prevention technologies, while continuing to support research, access, education, and partnerships aimed at helping end the HIV epidemic worldwide.
The announcement marks a potentially important step in expanding HIV prevention choices. If approved, once-weekly oral Yeztugo could offer a new long-acting pill-based PrEP option for people who may prefer less frequent oral dosing while avoiding or delaying injectable administration.
