Gilead Sciences, Inc. and Merck announced that the primary efficacy endpoint at Week 48 was met in both the Phase 3 ISLEND-1 and ISLEND-2 trials with the investigational oral once-weekly single-tablet HIV treatment regimen of islatravir/lenacapavir. The ISLEND trials are evaluating the efficacy and safety of islatravir 2 mg/lenacapavir 300 mg (ISL/LEN) in people with HIV who are virologically suppressed and switched from BIKTARVY (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets, B/F/TAF) (ISLEND-1) or standard of care antiretroviral regimens (ISLEND-2). The safety profile of ISL/LEN was generally comparable to the comparator regimens studied in the ISLEND trials, and no new safety concerns were identified.
Gilead and Merck plan to file the Phase 3 data from the ISLEND trials with regulatory authorities globally and submit the detailed findings for presentation at a future scientific congress. The primary efficacy endpoint of 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. In the double-blind ISLEND-1 trial, the once-weekly, single-tablet regimen of ISL/LEN was found to be statistically non-inferior to BIKTARVY.
In the open-label ISLEND-2 trial, ISL/LEN was found to be statistically non-inferior to standard of care daily oral antiretroviral therapy regimens. The safety profile of ISL/LEN was generally comparable to BIKTARVY in ISLEND-1 and to standard of care antiretroviral regimens in ISLEND-2. The combination of islatravir and lenacapavir targets multiple stages of HIV-1 replication, potentially offering people with HIV who are virologically suppressed a novel, long-acting oral single-tablet regimen. The potency and pharmacokinetic profiles of islatravir and lenacapavir enable long-acting dosing as a once-weekly tablet for HIV treatment, if approved.
Islatravir and lenacapavir in combination are investigational and not approved for use. ISLEND-1 (NCT06630286) is a Gilead-sponsored, multicenter Phase 3 randomized, double-blind, active-controlled trial designed to evaluate the safety and efficacy of switching to a once-weekly tablet of islatravir/lenacapavir (ISL/LEN) versus continuing treatment with BIKTARVY (bictegravir/emtricitabine/tenofovir alafenamide) in people with virologically suppressed HIV (HIV-1 RNA levels <50 copies/mL). ISLEND-2 (NCT06630299) is a Gilead-sponsored, multicenter Phase 3 randomized, open-label, active-controlled trial evaluating the safety and efficacy of switching to a once-weekly tablet of ISL/LEN versus continuation of standard of care treatment in people with virologically suppressed HIV (HIV-1 RNA levels <50 copies/mL).
Lenacapavir is being evaluated as a long-acting option in multiple ongoing and planned early and late-stage clinical studies in Gilead?s HIV treatment and prevention research program. Islatravir (MK-8591) is Merck?s potent, next-generation nucleoside analog that blocks HIV-1 replication by multiple mechanisms including inhibition of reverse transcriptase translocation, resulting in immediate chain termination, and induction of structural changes in the viral DNA (delayed chain termination). Islatravir is anchoring multiple ongoing early and late-stage clinical trials of two-drug regimens in combination with other Merck antiretrovirals for potential treatments for HIV-1. Islatravir is being studied in Phase 3 in combination with Merck?s doravirine (DOR/ISL) as a once-daily pill for treatment of HIV-1 infection in adults with no prior antiviral treatment history and in Phase 2b in combination with Merck?s investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) ulonivirine (MK-8507) as an oral once-weekly treatment for HIV-1.
