Gilead, Merck once-weekly HIV pill succeeds in Phase 3

Gilead and Merck said Sunday their once-weekly HIV combination pill met primary efficacy endpoints in both the ISLEND-1 and ISLEND-2 Phase 3 trials.stocktitan+1
The regimen pairs Merck's islatravir with Gilead's lenacapavir; both trials showed non-inferiority to daily standard-of-care regimens at 48 weeks with no new safety signals.stocktitan
The companies plan to file for regulatory approval globally, which would make it the first oral HIV treatment requiring only one pill per week.stocktitan

Gilead Sciences and Merck announced on Sunday that their investigational once-weekly combination pill of islatravir and lenacapavir met its primary efficacy endpoint in two Phase 3 trials, marking a potential milestone in HIV treatment as the first long-acting oral therapy for people living with the virus.stocktitan+1

The ISLEND-1 and ISLEND-2 trials evaluated the single-tablet regimen of islatravir 2 mg/lenacapavir 300 mg in virologically suppressed adults who switched from either Biktarvy, the widely used daily pill, or other standard-of-care antiretroviral regimens. In both studies, the once-weekly pill was found to be statistically non-inferior to the daily comparators at Week 48, with a comparable safety profile and no new safety concerns identified.stocktitan

A New Class of Convenience

The combination pairs Merck's islatravir, a next-generation nucleoside analog that blocks HIV replication through reverse transcriptase translocation inhibition, with Gilead's lenacapavir, a first-in-class capsid inhibitor that disrupts the virus at multiple stages of its lifecycle. Their pharmacokinetic profiles enable the long-acting once-weekly dosing.stocktitan

"Long-acting oral therapies represent a new wave of transformational innovation in HIV drug development, with the potential to reshape the landscape of care," said Jared Baeten, Senior Vice President of Clinical Development at Gilead Sciences. "Innovative oral HIV treatment options that allow for less frequent dosing may make a meaningful difference in the lives of people living with the virus, potentially offering more flexibility and discretion."stocktitan

Path to Approval

The companies plan to file the data with regulatory authorities globally and submit detailed findings for presentation at a future scientific congress. If approved, the combination would become the first oral HIV treatment dosed once weekly, moving beyond the current standard of daily pills.stocktitan

The results build on Phase 2 data presented at HIV Drug Therapy Glasgow 2024, which showed 94.2% of participants on the weekly regimen maintained viral suppression at 48 weeks, compared to 92.3% on daily Biktarvy. No virologic rebound or treatment resistance was detected in that earlier study.hivglasgow+2

Broader Landscape

The announcement comes amid an active period for long-acting HIV research. Gilead separately reported positive Phase 3 results earlier this year for a daily bictegravir/lenacapavir combination at CROI 2026, while Merck recently secured data supporting a regulatory filing for its daily doravirine/islatravir pill. The once-weekly regimen represents the most ambitious step yet toward reducing dosing frequency for oral HIV treatment.thebodypro+2

"By advancing this investigational novel once-weekly oral regimen of islatravir and lenacapavir, we aim to bring forward a new long-acting oral option that, if approved, would represent the first of its kind," said Dr. Eliav Barr, Senior Vice President and Chief Medical Officer at Merck Research Laboratories.stocktitan

Sources (50)