Gilead Sciences announced that the U.S. Food and Drug Administration (FDA) accepted its supplemental New Drug Application (sNDA) for Yeztugo as a potential once-weekly oral formulation for HIV prevention. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) action date of February 2, 2027, to review the application for the 300-mg tablet used as pre-exposure prophylaxis (PrEP).

The submission is supported by the clinical profile of lenacapavir, the active ingredient in Yeztugo. Data from the PURPOSE 1 and PURPOSE 2 trials demonstrated high efficacy in HIV prevention across diverse populations, including cisgender women, cisgender men, and gender-diverse people. If approved, this once-weekly oral option could become the first long-acting oral PrEP available.

Dietmar Berger, Chief Medical Officer at Gilead Sciences, stated that the filing reflects the company's commitment to advancing new HIV prevention options. He noted that nearly one year after the approval of twice-yearly Yeztugo, the company aims to extend the impact of its long-acting innovation into new formulations to broaden how HIV prevention is delivered.

Currently, lenacapavir oral tablets are approved within the Yeztugo regimen as an initial loading dose and as bridge therapy when administration of the every-six-month injections is delayed. The once-weekly oral formulation for PrEP remains investigational and is not approved anywhere globally.

About Lenacapavir

Lenacapavir is approved in multiple countries as PrEP to reduce the risk of sexually acquired HIV in adults and adolescents at risk of acquisition. It is also approved for the treatment of multi-drug-resistant HIV in adults in combination with other antiretrovirals. The drug features a multi-stage mechanism of action designed to inhibit HIV at multiple stages of its lifecycle, with no known cross-resistance to other existing drug classes in vitro.

Gilead Sciences Inc. and Merck & Co. Inc. discontinued the Phase 3 KEYNOTE-D46/EVOKE-03 trial evaluating the combination of Trodelvy and Keytruda for previously untreated metastatic non-small cell lung cancer with high PD-L1 expression. The decision followed a review by a Data Monitoring Committee of progression-free survival and interim overall survival data. While the combination showed a numerical improvement in progression-free survival, it did not reach statistical significance, and investigators determined the probability of achieving a meaningful overall survival benefit at final analysis was low. The safety profile remained consistent with known profiles, with no new signals identified.

Separately, the companies announced positive Phase 3 results for an investigational once-weekly oral HIV regimen combining islatravir and lenacapavir. The regimen met its primary efficacy endpoint in two studies, ISLEND-1 and ISLEND-2, which evaluated its safety and efficacy in people living with HIV who were already virologically suppressed.

HIV Trial Results

The primary endpoint in both studies measured the percentage of participants with HIV-1 RNA levels of at least 50 copies/mL at Week 48 under the FDA snapshot algorithm. In the ISLEND-1 study, patients switched from Biktarvy to the once-weekly islatravir/lenacapavir regimen. The treatment was found to be statistically non-inferior to Biktarvy. Meanwhile, in the open-label ISLEND-2 trial, the regimen demonstrated statistical non-inferiority compared with standard-of-care daily oral antiretroviral therapies.

The safety profile of the combination was generally comparable to the comparator regimens in both studies, with no new safety concerns identified.

Next Steps for HIV Treatment

Gilead and Merck plan to submit the Phase 3 findings to regulatory authorities worldwide and present detailed data at a future scientific congress. The investigational combination targets multiple stages of HIV-1 replication. If approved, the treatment could offer virologically suppressed patients a long-acting, once-weekly oral single-tablet option.