Merck’s Doravirine/Islatravir Receives FDA Acceptance for HIV Treatment

The U.S. Food and Drug Administration (FDA) has accepted a Fresh Drug Application (NDA) for Merck’s investigational, once-daily oral two-drug regimen, doravirine/islatravir (DOR/ISL), for the treatment of adults with HIV-1 infection who are virologically suppressed on antiretroviral therapy. The FDA has set a target action date of April 28, 2026, for the application under the Prescription Drug User Fee Act (PDUFA).

A Potential New Option for HIV Treatment

DOR/ISL, a combination of doravirine (100 mg) and islatravir (0.25 mg), is being developed as a complete regimen for individuals living with HIV-1. If approved, it would be the first FDA-approved two-drug regimen without an integrase inhibitor, offering a new option for those requiring a change to their antiretroviral therapy [1].

Clinical Trial Results

Phase 3 pivotal trial data demonstrated that DOR/ISL exhibited non-inferior efficacy and a generally comparable safety profile to a three-drug regimen based on an integrase inhibitor (BIC/FTC/TAF) [2]. Earlier trials, including a phase 3 study (NCT04233879), showed DOR/ISL (100/0.75 mg) was non-inferior to bictegravir/emtricitabine/tenofovir alafenamide through week 48 for initial HIV-1 treatment [3]. However, enrollment in that trial was stopped early due to CD4 and lymphocyte count decreases observed in other islatravir studies [3].

Addressing INSTI Resistance Concerns

With increasing concerns about the potential development of widespread resistance to integrase strand transfer inhibitors (INSTIs), a commonly used class of HIV medications, DOR/ISL could provide a valuable alternative. The development of this regimen reflects Merck’s commitment to innovating and delivering new options to meet the evolving needs of the HIV community [2].

Looking Ahead

The FDA’s acceptance of the NDA marks a significant step forward in the potential availability of a new treatment option for people living with HIV-1. The target action date of April 28, 2026, will be closely watched by the HIV community as they await a decision on this promising investigational regimen [4].