RAHWAY, N.J. — Merck on Tuesday announced late-breaking results from three Phase 3 clinical trials evaluating its investigational, once-daily, two-drug regimen doravirine/islatravir (DOR/ISL) for the treatment of adults living with HIV-1, with data presented at the 33rd Conference on Retroviruses and Opportunistic Infections in Denver.
The studies showed that DOR/ISL is the first non-INSTI, two-drug regimen to demonstrate non-inferior efficacy and a comparable safety profile to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) at Week 48 in adults who had not previously received antiretroviral therapy. Additional data showed that DOR/ISL maintained virologic suppression through Week 96 in adults who switched from other oral antiretroviral regimens, including BIC/FTC/TAF.
“We are proud to continue building on our 40-year history of HIV research with the presentation of compelling new data from our HIV pipeline at CROI this year,” said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer at Merck Research Laboratories. “Islatravir blocks HIV-1 replication through multiple mechanisms and could serve as the anchor for a series of two-drug, non-INSTI, daily and weekly treatment regimens. If approved, DOR/ISL may provide an important new option to help meet the evolving treatment needs of people living with HIV.”
In the Phase 3 MK-8591A-053 trial involving treatment-naïve adults, 91.8% of participants receiving DOR/ISL achieved viral suppression at Week 48 compared with 90.6% of those receiving BIC/FTC/TAF, meeting the study’s primary endpoint for non-inferiority. The safety profile was similar between treatment groups, with comparable rates of drug-related adverse events and treatment discontinuations. These findings are being published simultaneously in The Lancet HIV and are expected to support future regulatory submissions.
“These new Phase 3 results are meaningful, showing that an investigational two-drug regimen without an INSTI demonstrated non-inferior efficacy and a comparable safety profile versus BIC/FTC/TAF in previously untreated adults with HIV-1, including those with advanced disease,” said Dr. Jürgen K. Rockstroh, professor of medicine and head of the HIV Outpatient Clinic at the University of Bonn. He noted that the trial included a diverse global population, including participants with high viral loads and low CD4 counts.
Merck also presented new 96-week data from the Phase 3 MK-8591A-052 and MK-8591A-051 trials, which evaluated switching virologically suppressed adults to DOR/ISL from BIC/FTC/TAF or other baseline antiretroviral therapies. In both studies, participants who switched to DOR/ISL maintained high rates of viral suppression through Week 96, with safety outcomes comparable to standard therapies.
The 48-week data from these switch studies supported Merck’s New Drug Application for DOR/ISL in virologically suppressed adults. The U.S. Food and Drug Administration has set a target action date of April 28, 2026, under the Prescription Drug User Fee Act.
“As people living with HIV age, managing other health conditions becomes a reality for many,” said Dr. Amy Colson, director of research at Community Resource Initiative in Cambridge, Massachusetts. “These 96-week data are encouraging, showing a non-INSTI option like investigational DOR/ISL could offer an important alternative for people who need flexibility in their treatment over time.”
Merck said it continues to evaluate islatravir across multiple early- and late-stage clinical programs, including potential daily, weekly, and monthly treatment and prevention options, as part of its broader HIV research and development strategy.
