Gilead and Merck: Phase 3 ISLEND trials show positive topline results for once‑weekly islatravir/lenacapavir

Topline results

The Phase 3 ISLEND‑1 and ISLEND‑2 trials met their primary efficacy endpoint at Week 48 using the FDA snapshot algorithm (proportion with HIV‑1 RNA ≥50 copies/mL). In ISLEND‑1 (double‑blind), the once‑weekly single‑tablet islatravir/lenacapavir regimen was statistically non‑inferior to Biktarvy. In ISLEND‑2 (open‑label), the regimen was statistically non‑inferior to participants' daily standard‑of‑care antiretroviral regimens.

Regimen and study design

The investigational tablet contains islatravir 2 mg and lenacapavir 300 mg administered once weekly. ISLEND‑1 randomized virologically suppressed participants on Biktarvy 1:1 to switch or continue; ISLEND‑2 randomized participants on stable standard‑of‑care regimens to switch or continue. Key secondary endpoints include Week 96 viral outcomes, CD4 change and discontinuations for treatment‑emergent adverse events.

Safety and next steps

ISL/LEN's safety profile was reported as generally comparable to Biktarvy and to standard‑of‑care arms, with no new safety concerns identified. Gilead and Merck plan to file the Phase 3 data with regulatory authorities globally and to present detailed findings at a future scientific congress.

Mechanism and status

The combination targets multiple stages of HIV‑1 replication; islatravir is a next‑generation nucleoside analog and lenacapavir is a capsid inhibitor. The combination remains investigational and is not approved for use.