Merck (known as MSD outside the U.S. and Canada) has reported encouraging topline results from a pivotal Phase 3 clinical trial evaluating its once-daily, two-drug oral regimen doravirine/islatravir (DOR/ISL 100 mg/0.25 mg) in treatment-naïve adults with HIV-1. The combination successfully met both its primary efficacy and safety goals, advancing Merck’s pursuit of simplified yet effective HIV treatment options.
A New Option for First-Line HIV Treatment
The Phase 3 trial (MK-8591A-053) compared DOR/ISL to the widely used three-drug integrase inhibitor regimen BIC/FTC/TAF (bictegravir/emtricitabine/tenofovir alafenamide).
Key findings at Week 48:
- DOR/ISL achieved non-inferiority to BIC/FTC/TAF in reducing HIV-1 RNA to <50 copies/mL.
- The investigational regimen’s safety profile was comparable to the three-drug control arm.
- Both efficacy and safety endpoints met their predefined success criteria.
Merck noted that full data will be presented at an upcoming scientific conference.
Regulatory Momentum: FDA NDA Accepted
The U.S. FDA has already accepted Merck’s New Drug Application (NDA) for DOR/ISL.
The application covers use of the regimen in:
- Adults with HIV-1 who are virologically suppressed and wish to switch therapies.
A PDUFA target action date of April 28, 2026, has been assigned.
Doravirine is already FDA-approved as:
- Pifeltro® (single-agent NNRTI)
- Delstrigo® (doravirine + lamivudine + TDF)
Inside the Phase 3 MK-8591A-053 Study
The study enrolled 537 treatment-naïve adults, randomized 1:1 to either:
- DOR/ISL (two-drug regimen)
- BIC/FTC/TAF (three-drug INSTI-based regimen)
Study design highlights:
- Double-blind, active-controlled
- Primary analysis at Week 48
- Participants will remain blinded through Week 144
- Week 96 data planned for future release
- Optional open-label extension to Week 240
The trial assessed:
- % of participants achieving viral suppression (<50 copies/mL)
- Adverse events and discontinuations due to safety concerns
How Islatravir Works?
Islatravir (MK-8591) is Merck’s investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI). It blocks HIV replication through multiple mechanisms:
- Inhibits reverse transcriptase translocation
- Causes immediate chain termination
- Induces structural changes in viral DNA
Its potency and resistance profile make it a promising backbone agent for both daily and once-weekly HIV treatment strategies.
Additional Ongoing Trials
Merck is conducting several other late-stage studies involving DOR/ISL:
Switch Studies
- MK-8591A-051: Switching from current ART to DOR/ISL (NCT05631093)
- MK-8591A-052: Switching from BIC/FTC/TAF (NCT05630755)
Extension Studies
- MK-8591A-054: Open-label evaluation in participants from earlier Phase 3 trials (NCT05766501)
Combination Regimens in Development
- Islatravir + Lenacapavir (Gilead): Once-weekly oral treatment (Phase 3)
- Islatravir + Ulonivirine (Merck NNRTI): Once-weekly regimen in Phase 2b
Beyond Treatment: Advancing HIV Prevention
Merck is also advancing MK-8527, a once-monthly oral NRTTI for HIV pre-exposure prophylaxis (PrEP).
Two major global PrEP trials are underway:
- EXPrESSIVE-11: Evaluating efficacy in individuals with high HIV exposure risk (NCT07044297)
- EXPrESSIVE-10: Focused on women and adolescent girls in sub-Saharan Africa (NCT07071623), supported by the Gates Foundation
A Long Commitment to HIV Innovation
For more than 35 years, Merck has contributed to major advances in HIV treatment—from early breakthroughs to modern optimized regimens. Today, the company continues to expand its antiviral pipeline, aiming to:
- Improve long-term HIV management
- Develop next-generation long-acting and simplified regimens
- Support global efforts to help end the HIV epidemic
As Merck’s Chief Medical Officer Dr. Eliav Barr stated, the new data underscore the potential of DOR/ISL to serve as a meaningful treatment option, whether for those starting ART for the first time or switching from an existing regimen.
