Gilead Sciences, Inc. and Merck, known as MSD outside of the United States and Canada, announced that the primary efficacy endpoint at Week 48 was met in both the Phase 3 ISLEND-1 and ISLEND-2 trials for the investigational oral once-weekly single-tablet regimen of islatravir 2 mg and lenacapavir 300 mg. The trials evaluated the regimen in people with HIV who are virologically suppressed and switched from BIKTARVY or standard of care antiretroviral regimens. The regimen demonstrated statistical non-inferiority compared to BIKTARVY in the double-blind ISLEND-1 trial and to standard of care daily oral antiretroviral therapy in the open-label ISLEND-2 trial. The safety profile of islatravir/lenacapavir was generally comparable to the comparator regimens studied in the ISLEND trials, with no new safety concerns identified. Gilead and Merck plan to file the Phase 3 data with regulatory authorities globally and submit the detailed findings for presentation at a future scientific congress.

Trial Details and Endpoints

The primary efficacy endpoint for both ISLEND-1 and ISLEND-2 was the percentage of participants with HIV-1 RNA levels ≥ 50 copies/mL at Week 48, defined by the FDA snapshot algorithm. Key secondary endpoints included virologic suppression rates at Week 48 and Week 96, changes in CD4 cell count, and discontinuation due to treatment-emergent adverse events.

Mechanism of Action

Islatravir is Merck's next-generation nucleoside analog that blocks HIV-1 replication by inhibiting reverse transcriptase translocation. Lenacapavir is Gilead's first-in-class capsid inhibitor designed to inhibit HIV at multiple stages of its lifecycle. The combination targets multiple stages of HIV-1 replication, enabling long-acting dosing as a once-weekly tablet.

Jared Baeten, Senior Vice President of Clinical Development at Gilead Sciences, stated that long-acting oral therapies represent a transformational innovation with the potential to reshape HIV care. Dr. Eliav Barr, Senior Vice President and Chief Medical Officer at Merck Research Laboratories, emphasized the commitment to advancing a novel once-weekly oral option to expand treatment choices for people living with HIV.