Merck's Doravirine/Islatravir Receives FDA Approval for HIV Treatment

The FDA has accepted Merck's NDA for doravirine/islatravir, a once-daily oral HIV-1 treatment for adults with virologically suppressed HIV-1 infection. The investigational regimen demonstrated non-inferior efficacy in Phase 3 trials compared to traditional regimens. The FDA's target action date is set for April 28, 2026.

The U.S. Food and Drug Administration (FDA) has accepted for review Merck's New Drug Application (NDA) for doravirine/islatravir (DOR/ISL), a once-daily oral two-drug regimen for adults with HIV-1 infection that is virologically suppressed on antiretroviral therapy. This acceptance marks a significant milestone in HIV treatment, as DOR/ISL demonstrated non-inferior efficacy and a generally comparable safety profile to traditional three-drug regimens in Phase 3 clinical trials [1].

The FDA has set a target action date of April 28, 2026, for the application under the Prescription Drug User Fee Act (PDUFA). Merck's submission is based on findings from two pivotal Phase 3 clinical trials, MK-8591A-051 and MK-8591A-052. In these trials, DOR/ISL was shown to be non-inferior to baseline antiretroviral therapy (bART) in the open-label trial MK-8591A-051 and non-inferior to bictegravir/emtrictabine/tenofovir alafenamide (BIC/FTC/TAF) in the double-blind trial MK-8591A-052. The safety profile of DOR/ISL was generally comparable to comparator baseline antiretroviral regimens in both trials [1].

Islatravir (MK-8591), the investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI) component of DOR/ISL, blocks HIV-1 replication by inhibiting reverse transcriptase translocation, resulting in immediate chain termination and induction of structural changes in the viral DNA, leading to delayed chain termination. Merck's commitment to researching NRTTIs includes multiple ongoing clinical trials evaluating islatravir in combination with other antiretrovirals for potential daily and once-weekly treatments for HIV-1 [1].

This approval could potentially simplify HIV treatment regimens for patients, reducing the complexity of medication schedules and improving adherence. It also aligns with Merck's longstanding commitment to HIV research and development, which has led to transformational innovations and collaborations aimed at ending the HIV epidemic.

References:
[1] Merck. (2025). U.S. FDA accepts new drug application for Merck's doravirine/islatravir. Retrieved from https://www.merck.com/news/u-s-fda-accepts-new-drug-application-for-mercks-doravirine-islatravir-an-investigational-once-daily-oral-two-drug-regimen-for-treatment-of-adults-with-virologically-suppressed-hiv-1-infe/