Gilead and Merck Once-Weekly Oral HIV Regimen Meets Phase 3 Endpoints

Gilead and Merck Once-Weekly Oral HIV Regimen Meets Phase 3 Endpoints

In a major milestone for long-acting HIV therapeutics, Gilead Sciences and Merck announced positive topline Week 48 results from two pivotal Phase 3 trials, ISLEND-1 and ISLEND-2. The trials evaluated an investigational, once-weekly oral single-tablet combination of islatravir (Merck's next-generation nucleoside reverse transcriptase translocation inhibitor) and lenacapavir (Gilead's first-in-class capsid inhibitor). If approved, this combination would represent the first long-acting oral HIV treatment taken only once per week, offering a highly discrete and flexible alternative to daily antiretroviral therapy (ART).¹

Both trials successfully met their primary efficacy endpoints, demonstrating that switching to the once-weekly oral regimen maintained viral suppression (HIV-1 RNA < 50 copies/mL) at Week 48:

• ISLEND-1 (NCT06630286): A double-blind, active-controlled trial evaluating virologically suppressed patients switching from daily Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide). Once-weekly islatravir/lenacapavir (ISL/LEN) was found to be statistically non-inferior to continuing daily Biktarvy.
• ISLEND-2 (NCT06630299): An open-label, active-controlled trial evaluating virologically suppressed patients switching from various daily standard-of-care antiretroviral regimens. Once-weekly ISL/LEN demonstrated statistical non-inferiority to continuation of daily standard-of-care ART.

The safety and tolerability profile of once-weekly ISL/LEN was generally comparable to both Biktarvy and standard-of-care regimens, with no new safety signals identified. The companies plan to file the Phase 3 data with global regulatory authorities and present detailed results at an upcoming scientific congress.