Gilead’s once-weekly oral Yeztugo (lenacapavir) for HIV prevention has been accepted for FDA review. The filing is supported by efficacy data from the PURPOSE 1 and PURPOSE 2 PrEP trials, with a decision expected in February 2027.
Written By: Disha Jadhao, BPharm
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration (FDA) has accepted a supplemental New Drug Application (sNDA) from Gilead Sciences for a once-weekly oral formulation of Yeztugo® (lenacapavir) as pre-exposure prophylaxis (PrEP) for HIV prevention. The agency assigned a Prescription Drug User Fee Act (PDUFA) target action date of February 2, 2027.
If approved, once-weekly oral Yeztugo would become the first long-acting oral PrEP option, offering an alternative to both daily oral regimens and injectable HIV prevention therapies.
The filing builds on the established clinical profile of lenacapavir, which received approval in the United States as a twice-yearly injectable PrEP regimen. The submission relies on efficacy and safety data generated through the pivotal PURPOSE 1 (NCT04994509) and PURPOSE 2 (NCT04925752) studies, which showed high levels of HIV prevention across diverse populations, including cisgender women, cisgender men, and gender-diverse individuals.
Expanding the Lenacapavir Platform
Lenacapavir belongs to a novel class of HIV capsid inhibitors and differs from currently approved antiretroviral therapies through its multi-stage mechanism of action. Rather than targeting a single phase of viral replication, the drug interferes with multiple steps of the HIV lifecycle.
The agent has shown no known in vitro cross-resistance with existing antiretroviral drug classes, supporting its potential utility across both HIV prevention and treatment settings.
Beyond PrEP, lenacapavir is approved in several countries for use in combination regimens for adults with multidrug-resistant HIV infection.
Clinical Evidence Supporting the Filing
The FDA submission draws on results from the PURPOSE clinical development program, which established lenacapavir’s effectiveness in preventing HIV acquisition among individuals at risk of infection.
PURPOSE 1 and PURPOSE 2 evaluated the therapy across geographically and demographically diverse populations. The studies demonstrated high efficacy in reducing HIV infections while supporting a favorable safety profile consistent with previous clinical experience.
Oral lenacapavir tablets already play a role within the approved Yeztugo regimen. They are currently used as an initiation loading dose and as temporary bridge therapy when scheduled six-month injections are delayed.
The latest filing seeks to expand that use into a standalone once-weekly PrEP regimen, potentially providing a lower-burden option for individuals who prefer oral treatment but do not wish to take medication daily.
Strategic Importance for HIV Prevention
Gilead views the submission as the next step in broadening HIV prevention access through multiple dosing formats. The company continues to advance lenacapavir as a foundational component of its HIV prevention and treatment portfolio, with ongoing studies exploring both oral and injectable approaches across various dosing schedules.
Chief Medical Officer Dietmar Berger said the filing reflects the need for greater flexibility in HIV prevention, noting that patient preferences vary widely and that additional PrEP options could help expand uptake among at-risk populations.
Implications for Future PrEP Access
The FDA is expected to complete its review by February 2, 2027. Until then, once-weekly oral lenacapavir remains investigational and has not received approval in any market.
Currently, Yeztugo® (lenacapavir) injection is approved in the United States for PrEP to reduce the risk of sexually acquired HIV-1 infection in adults and adolescents weighing at least 35 kilograms who have a confirmed negative HIV test before treatment initiation.
The regulatory decision could mark an important expansion of the HIV prevention landscape, introducing a new long-acting oral option between daily PrEP and twice-yearly injectable therapy.
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About the Writer
Disha Sanjay Jadhao (LinkedIn) is a pharmacy graduate and healthcare writer with a strong interest in clinical documentation and simplifying healthcare information for better reader understanding. She is enthusiastic, adaptable, and eager to take on new challenges while contributing to clear, accurate, and engaging medical and pharmaceutical content.