Key Takeaways
- FDA accepts New Drug Application for Merck’s doravirine/islatravir (DOR/ISL) HIV regimen: The once-daily, oral, two-drug regimen for virologically suppressed adults with HIV-1 is now under FDA review.
- DOR/ISL meets primary endpoints in two Phase III trials: Both studies showed non-inferiority to standard regimens in maintaining viral suppression at week 48, with comparable safety outcomes.
- First two-drug oral regimen without integrase inhibitor to show non-inferiority: If authorized, DOR/ISL would be the first approved HIV regimen of its kind, offering a simplified alternative for eligible patients.
The FDA has accepted a New Drug Application (NDA) for Merck’s doravirine/islatravir (DOR/ISL), an investigational, once-daily, oral, two-drug regimen for adults with virologically suppressed HIV-1 infection. According to the company, the filing was supported by data from the Phase III MK-8591A-051 and MK-8591A-052 trials, which showed that DOR/ISL was non-inferior to both baseline antiretroviral therapy and to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF).1
Could DOR/ISL Become the Next Complete Treatment Option for Virologically Suppressed Adults with HIV?
“Merck has been at the forefront of HIV research for more than 35 years and we are pleased to continue our work to innovate and deliver new options that aim to meet the needs of the HIV community,” said Eliav Barr, SVP, head, global clinical development, chief medical officer, Merck Research Laboratories, in a press release. “The health needs of people living with HIV often change over time—whether it’s managing comorbidities or navigating complex medication regimens. We believe DOR/ISL, if approved, will represent an important new complete regimen option designed to help meet their diverse needs.”
MK-8591A-051: DOR/ISL vs. Baseline Antiretroviral Therapy (bART) in Open-Label Trial
- The open-label, randomized, active-controlled MK-8591A-051 trial evaluated the efficacy and safety of a switch to investigational, oral, once-daily DOR/ISL in 551 adults with HIV-1 infection that has been virologically suppressed using bART.
- During the trial, patients were randomly assigned in a 2:1 ratio to switch to DOR/ISL or continue on bART. The primary endpoint of the trial was the percentage of participants with HIV-1 RNA ≥50 copies/mL at week 48.1
- Results showed that 1.4% of participants who received DOR/ISL had a viral load of ≥50 copies/mL at week 48 in comparison to 4.9% on bART.
- Additionally, 95.6% of participants who switched to DOR/ISL maintained viral suppression compared to 91.9% of participants who continued on bART.2
MK-8591A-052: DOR/ISL vs. BIC/FTC/TAF in Double-Blind Trial
- The double-blind, randomized, active-controlled MK-8591A-052 trial evaluated the efficacy and safety of a switch to investigational, oral, once-daily DOR/ISL in 513 adults with HIV-1 infection that has been virologically suppressed on BIC/FTC/TAF.
- Patients were randomly assigned in a 2:1 ratio to switch to DOR/ISL or continue treatment with BIC/FTC/TAF.
- The primary endpoint of the trial was the percentage of participants with HIV-1 RNA ≥50 copies/mL at week 48.1
- Results showed that 1.5% of patients who switched to DOR/ISL had a viral load of ≥50 copies/mL at week 48 compared to 0.6% on BIC/FTC/TAF.
- Additionally, 91.5% of participants who switched to DOR/ISL maintained viral suppression compared to 94.2% in the BIC/FTC/TAF group.
Safety Profile and Common Adverse Events (AEs)
- Safety findings were consistent with those of the comparator regimens.
- Rates of drug-related adverse events (AEs) as well as discontinuations were similar in both groups of the MK-8591A-052 trial.
- The most common AEs included arthralgia, COVID-19, nasopharyngitis, and fatigue.2
HIV in the United States: Context for Innovation
An estimated 1.2 million people in the United States are currently living with HIV, with 13% remaining unaware. However, the rate of new infections decreased by 12% between 2018 and 2022. In 2022, there were approximately 31,800 new cases of HIV diagnosed in the United States.3
“We are excited that DOR/ISL is the first two-drug regimen without an integrase inhibitor to demonstrate comparable efficacy and safety to the three-drug InSTI-based regimen, BIC/FTC/TAF, in a Phase III pivotal trial,” said Barr, in a March press release. “Merck has been a research pioneer in HIV for decades. These data and our work on the longer-acting islatravir-based therapies in our pipeline show our continued commitment to help find new options that address the evolving needs of people living with HIV.”
References
- U.S. FDA Accepts New Drug Application for Merck’s Doravirine/Islatravir, an Investigational, Once-Daily, Oral, Two-Drug Regimen for Treatment of Adults with Virologically Suppressed HIV-1 Infection. Merck. July 10, 2025. Accessed July 11, 2025. 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/
- Merck Announces Positive Data from Phase 3 Trials that Show the Investigational, Once-Daily, Oral, Two-Drug Regimen of Doravirine/Islatravir (DOR/ISL) Maintained HIV-1 Viral Suppression at Week 48. Merck. March 12, 2025. Accessed July 11, 2025. https://www.merck.com/news/merck-announces-positive-data-from-phase-3-trials-that-show-the-investigational-once-daily-oral-two-drug-regimen-of-doravirine-islatravir-dor-isl-maintained-hiv-1-viral-suppression-at-week-48/#:~:text=March%2012%2C%202025%2012:26%20pm%20ET.%20DOR/ISL,to%20comparator%20antiretroviral%20therapies%20in%20adults%20with
- U.S. Statistics. HIV.gov. Accessed July 11, 2025. https://www.hiv.gov/hiv-basics/overview/data-and-trends/statistics
