Merck's investigational, once-daily, oral, two-drug, single-tablet regimen of doravirine/islatravir (DOR/ISL) has shown positive results in two pivotal Phase 3 trials, offering a potential new option for adults with HIV-1 infection. The trials focused on individuals with virologically suppressed HIV-1, evaluating DOR/ISL against existing antiretroviral therapy regimens.
The trials, MK-8591A-051 and MK-8591A-052, assessed the efficacy and safety of DOR/ISL (100 mg/0.25 mg) in maintaining viral suppression, defined as HIV-1 RNA levels below 50 copies/mL at Week 48. The primary endpoint was met in both trials, demonstrating non-inferiority to baseline antiretroviral therapy (bART) in the open-label MK-8591A-051 trial and non-inferiority to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in the double-blind MK-8591A-052 trial. While DOR/ISL did not meet superiority criteria over BIC/FTC/TAF, both trials achieved their primary safety objectives.
Study Details and Patient Population
MK-8591A-051 enrolled 551 adults with virologically suppressed HIV-1, randomizing them 2:1 to either switch to DOR/ISL or continue their current bART regimen. MK-8591A-052 included 513 adults with similar viral suppression on BIC/FTC/TAF, also randomized 2:1 to switch to DOR/ISL or continue their existing regimen. Participants in MK-8591A-051 will receive DOR/ISL through Week 144, with eligible participants continuing until Week 240 or commercial availability. Those in MK-8591A-052 will remain on their randomized regimen through Week 144, with similar options for extended treatment.
Mechanism of Action and Clinical Significance
Doravirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), is already approved in the U.S. as Pifeltro and as part of the Delstrigo co-formulation. Islatravir, an investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI), inhibits both transcriptase and translocation, leading to chain termination. This combination offers a simplified, two-drug regimen, potentially reducing pill burden and improving adherence for people living with HIV.
Future Plans and Ongoing Research
Merck plans to present detailed findings from these trials at an upcoming scientific congress and submit the data to regulatory authorities for review. In addition to these trials, DOR/ISL is being evaluated in treatment-naïve individuals in the MK-8591A-053 trial and in an open-label extension study, MK-8591A-054, for participants from earlier Phase 3 trials.
"We are encouraged by the results from these Phase 3 trials evaluating a once-daily, oral, two-drug, single-tablet regimen of doravirine and islatravir," said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. "We are committed to advancing our clinical programs for islatravir in combination with other antiretrovirals as potential options to help address the needs of people living with HIV."
