Yeztugo® (Lenacapavir) Is the First and Only FDA-Approved HIV Prevention Option Offering 6 Months of Protection

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On Jun. 18, 2025, Gilead Sciences announced that the U.S. Food and Drug Administration (FDA) has approved Yeztugo® (lenacapavir)—the company’s injectable HIV-1 capsid inhibitor—as pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV in adults and adolescents weighing at least 35kg, making it the first and only twice-yearly option available in the United States for people who need or want PrEP. Data show that ≥99.9% of participants who received Yeztugo in the Phase 3 PURPOSE 1 and PURPOSE 2 trials remained HIV negative.

The first PrEP medication, which was also developed by Gilead, was approved in the U.S. in 2012. However, data from the Centers for Disease Control and Prevention (CDC) show that, in 2022 (the most recent year with available data), only about 1 in 3 (36%) people in the U.S. who met the CDC’s eligibility criteria for PrEP were prescribed a form of PrEP. CDC data show that all populations in the U.S. are not yet using PrEP at rates that could end transmission of the virus at the population level, with particular gaps for women, Black/African American and Hispanic/Latino people, and people in the U.S. South.

Data also show that barriers including adherence challenges, stigma and low awareness of existing PrEP options—by both healthcare providers and consumers—contribute to this low uptake of PrEP across multiple populations. The potential impact of this limited uptake, adherence and access is underscored by the fact that, in 2023, more than 100 people were diagnosed with HIV every day in the U.S.

The FDA approval of Gilead’s New Drug Applications (NDAs) for Yeztugo was supported by data from the Phase 3 PURPOSE 1 and PURPOSE 2 trials conducted by Gilead. In the PURPOSE 1 trial, data at the primary analysis showed twice-yearly subcutaneous Yeztugo demonstrated zero HIV infections among 2,134 participants in the Yeztugo group, 100% reduction in HIV infections and 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.

Yeztugo received FDA approval under Priority Review. Additionally, in October 2024, Yeztugo was granted Breakthrough Therapy Designation, which is intended to expedite the development and review of new drugs that may demonstrate substantial improvement over available therapy.

The multi-stage mechanism of action of lenacapavir is distinguishable from other currently approved classes of antiviral agents. While most antivirals act on just one stage of viral replication, lenacapavir is designed to inhibit HIV at multiple stages of its lifecycle and has no known cross resistance exhibited in vitro to other existing drug classes.

Lenacapavir is being evaluated as a long-acting option in multiple ongoing and planned early and late-stage clinical studies in Gilead’s HIV prevention and treatment research program. Lenacapavir is being developed as a foundation for potential future HIV therapies with the goal of offering both long-acting oral and injectable options with several dosing frequencies, in combination or as a mono agent, that help address individual needs and preferences of people and communities affected by HIV. The journal Science named lenacapavir its 2024 “Breakthrough of the Year.”

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Source: Gilead
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