Merck’s two-drug HIV regimen hits phase 3 success

The study successfully met its primary endpoint, demonstrating similar rates of viral suppression for DOR/ISL compared to Biktarvy at 48 weeks

Merck has announced positive topline results from a Phase 3 clinical trial showing that its experimental once-daily, oral, two-drug HIV regimen of doravirine/islatravir (DOR/ISL) was non-inferior to Gilead Sciences' three-drug standard of care, Biktarvy, in adults who had not previously received treatment.

The study successfully met its primary endpoint, demonstrating similar rates of viral suppression for DOR/ISL compared to Biktarvy at 48 weeks. The safety profile was also comparable.

"This is the first two-drug regimen without an integrase inhibitor to demonstrate efficacy and safety on par with a three-drug INSTI-based regimen in treatment-naïve adults,” said Dr. Eliav Barr, Merck’s Chief Medical Officer. “These data highlight the potential of DOR/ISL as a meaningful treatment option for both new patients and those looking to switch regimens.”

In a related regulatory move, the U.S. Food and Drug Administration (FDA) has accepted Merck’s New Drug Application for DOR/ISL as a potential replacement therapy for virologically suppressed adults, setting a target action date of April 28, 2026. Doravirine is already approved in the U.S. as a single agent (PIFELTRO) and in combination therapy (DELSTRIGO).

Islatravir, Merck’s investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI), blocks HIV replication through multiple mechanisms, offering potent antiviral activity with a strong resistance profile. Ongoing trials are evaluating DOR/ISL in switch studies and in combination with other novel agents, including once-weekly regimens, signalling a potential shift in HIV treatment toward simplified, high-potency therapies.