Gilead Sciences (Nasdaq: GILD) and Merck (NYSE: MRK) reported that the investigational islatravir lenacapavir HIV treatment met its primary efficacy endpoint in both Phase III ISLEND trials, a result that positions the combination as a potential first approved long-acting oral HIV treatment taken once weekly. The topline data, drawn from two distinct switch populations, demonstrated non-inferiority to current standard-of-care regimens at Week 48 — a milestone that sets the stage for regulatory submissions globally.
The combination pairs islatravir, Merck's nucleoside analog that blocks HIV-1 replication through reverse transcriptase translocation inhibition, with lenacapavir, Gilead's first-in-class capsid inhibitor HIV therapy that disrupts viral replication across multiple stages of the lifecycle. The pharmacokinetic profiles of both agents support once-weekly oral dosing, a meaningful departure from the daily tablet regimens that have defined HIV treatment for decades.
Trial data
The ISLEND-1 and ISLEND-2 trials together constitute the core Phase III HIV clinical trial program for the ISL/LEN regimen, each addressing a distinct patient population of virologically suppressed adults — defined as HIV-1 RNA levels below 50 copies/mL — who switched from an existing antiretroviral regimen.
ISLEND-1 is a multicenter, randomized, double-blind, active-controlled study in which participants on Gilead's Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) for at least six months were randomized 1:1 to switch to once-weekly ISL/LEN or continue daily bictegravir/emtricitabine/tenofovir alafenamide. The primary endpoint — the proportion of participants with HIV-1 RNA at or above 50 copies/mL at Week 48 by the FDA snapshot algorithm — was met, with ISL/LEN demonstrating statistical non-inferiority to bictegravir/emtricitabine/tenofovir alafenamide. The safety profile was described as generally comparable to the comparator, with no new safety signals identified.
ISLEND-2, an open-label, randomized, active-controlled study, enrolled virologically suppressed adults switching from a broader range of stable standard-of-care antiretroviral regimens — including integrase strand transfer inhibitors, nucleoside reverse transcriptase inhibitors, boosted protease inhibitors, and non-nucleoside reverse transcriptase inhibitors. ISL/LEN was again statistically non-inferior to continued daily oral antiretroviral therapy at Week 48, with a comparable tolerability profile. Key secondary endpoints across both trials include virologic suppression rates and virologic failure rates at Week 96, CD4 cell count changes, and treatment discontinuation due to adverse events — data that remain pending as both studies continue to follow participants.