Gilead's Lenacapavir Advances: FDA Accepts Weekly Oral PrEP Application, Global Access Expands
The U.S. FDA has accepted Gilead's application for an investigational once-weekly oral lenacapavir for HIV prevention, with a review date set for February 2027. Concurrently, PEPFAR and The Global Fund are expanding access to the twice-yearly injectable version to a total of 3 million people by 2028. Gilead will present new data on both lenacapavir and a novel bictegravir/lenacapavir combination at CROI 2026.
The U.S. Food and Drug Administration has accepted Gilead Sciences' supplemental New Drug Application (sNDA) for an investigational once-weekly oral formulation of lenacapavir (brand name Yeztugo) for HIV prevention as pre-exposure prophylaxis (PrEP). The FDA has assigned a Prescription Drug User Fee Act (PDUFA) action date of February 2, 2027, for the application. If approved, this would become the first long-acting oral PrEP option.
The submission is supported by the established clinical profile of lenacapavir, with high efficacy demonstrated across two Phase 3 trials, PURPOSE 1 and PURPOSE 2, in diverse global populations including cisgender women, cisgender men, and gender-diverse people. Lenacapavir oral tablets are already approved for use within the Yeztugo regimen as an initial loading dose and as a bridge therapy when administration of every-six-month injections are delayed. The once-weekly oral formulation remains investigational and is not approved anywhere globally.
In parallel, global access to the approved twice-yearly injectable lenacapavir is being significantly expanded. The U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) and The Global Fund are making an additional investment to expand access for up to an additional 1 million people, bringing the total commitment to 3 million people in high-incidence, resource-limited countries through 2028. Lenacapavir is the first HIV prevention therapy to reach communities in sub-Saharan Africa in the same year it was approved in the United States, with initial shipments arriving at the end of 2025.
Gilead is providing lenacapavir at no profit to the Global Fund and PEPFAR in countries with the most urgent need today. The company's broader global access strategy includes voluntary licensing agreements with six generic manufacturers, with large-scale generic rollout expected to begin in 2027. This expansion comes as approximately 1.3 million new HIV infections occur globally each year.
Gilead will also present new clinical data from its HIV treatment and prevention portfolio at the 33rd Conference on Retroviruses and Opportunistic Infections (CROI 2026), to be held February 22-25 in Denver, Colorado. Notably, late-breaking abstracts include Phase 3 results from the ARTISTRY-1 and ARTISTRY-2 trials exploring the efficacy and safety of an investigational, single-tablet combination regimen of bictegravir 75 mg and lenacapavir 50 mg for HIV treatment. These studies evaluated the regimen in people living with HIV who are virologically suppressed and switched from their prior antiretroviral therapy.
Additional research to be presented includes data on islatravir plus lenacapavir, which has the potential to be the first weekly oral HIV treatment regimen, and on lenacapavir in combination with broadly neutralizing antibodies for a potential twice-yearly HIV treatment regimen. In prevention research, Gilead will share further data from the PURPOSE program on the safety and efficacy of twice-yearly subcutaneous lenacapavir for PrEP, updates on its resistance profile, and the design of a Phase 3 trial for an investigational once-yearly intramuscular formulation.