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Merck Announces Positive Topline Results from the Pivotal Phase 3 Trial Evaluating Investigational, Once-Daily, Oral, Two-Drug, Single-Tablet Regimen of Doravirine/Islatravir (DOR/ISL) in Treatment-Naïve Adults with HIV-1 Infection
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• Efficacy and Safety by Age After Switch to Doravirine/Islatravir (100 mg/0.25 mg) Once Daily: Week 48 Results From Two Phase 3 Randomized, Active-Controlled Studies in Adults Living With HIV-1 - (10/23/25)
• Safety and Efficacy of Doravirine/Islatravir (DOR/ISL) 100/0.25 mg Once Daily (QD) After ISL Dose Reduction From 0.75 mg: Week 48 Results From an Open-Label Phase 3 Study - (10/23/25)
• Modeling Confirms Islatravir 0.25 mg Administered Daily Has No Adverse Effect on Total Lymphocyte or CD4+ T-Cell Counts in People Living With HIV - (10/23/25)
November 19, 2025 6:45 am EST
Investigational DOR/ISL is the first non-INSTI, two-drug regimen to demonstrate non-inferiority to BIC/FTC/TAF in a Phase 3 clinical trial in treatment-naïve adults with HIV-1 infection
RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced topline results from the pivotal double-blind Phase 3 trial of the investigational, once-daily, oral, two-drug, single-tablet regimen of doravirine/islatravir [DOR/ISL (100 mg/0.25 mg)] in adults with HIV-1 infection who had not previously received antiretroviral treatment (treatment-naïve) (MK-8591A-053). The success criterion for the primary efficacy hypothesis, as measured by the percentage of participants with HIV-1 RNA levels <50 copies/mL at Week 48, was met, with DOR/ISL demonstrating non-inferiority to once-daily oral bictegravir/emtricitabine/tenofovir alafenamidei [BIC/FTC/TAF (50 mg/200 mg/25 mg)]. The primary safety objective of the trial was also met, with the safety profile of DOR/ISL being comparable to BIC/FTC/TAF.
The company is planning to present detailed findings from this trial at a future scientific congress and to submit applications including these data to health authorities. The U.S. Food and Drug Administration (FDA) accepted the New Drug Application (NDA) for DOR/ISL for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in those who are virologically-suppressed on a stable antiretroviral regimen and has set a target action date of April 28, 2026, for the application under the Prescription Drug User Fee Act (PDUFA). In the U.S., doravirine is approved for the treatment of adults with HIV-1 in combination with other antiretrovirals as a single agent (PIFELTRO) and a component of a single-tablet regimen [DELSTRIGO; doravirine, lamivudine, and tenofovir disoproxil fumarate (DOR/3TC/TDF)].
"We are encouraged by the results from this Phase 3 trial with DOR/ISL, evaluating the regimen in adults with HIV who have not previously taken antiretroviral treatments. DOR/ISL is the first two-drug regimen without an integrase inhibitor showing non-inferior efficacy and safety when compared to the three-drug INSTI-based regimen BIC/FTC/TAF in this population," said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. "These data support the potential for this regimen to be a meaningful treatment option for virally suppressed people living with HIV who are looking to switch to a new regimen or people who have not previously been on antiretroviral therapy to start treatment."
About MK-8591A-053 (NCT05705349)
MK-8591A-053 is a Phase 3, randomized, active-controlled, double-blind, clinical trial designed to evaluate the antiretroviral activity, safety, and tolerability of once-daily DOR/ISL (100 mg/0.25 mg) in treatment-naïve adults with HIV-1 infection compared to the once-daily 3-drug combination of BIC/FTC/TAF. Participants (n=537) were randomized 1:1 to either investigational DOR/ISL or BIC/FTC/TAF regimen through Week 48. Participants will continue in the double blinded study through Week 144, with a readout planned at Week 96. After Week 144, eligible participants will be given an option to continue in an open label extension and receive DOR/ISL until Week 240 or when DOR/ISL becomes commercially accessible (whichever comes first). The primary efficacy (percentage of participants with HIV-1 RNA levels <50 copies/mL) and safety (number of participants experiencing adverse events (AEs) and discontinuing trial intervention due to AEs) endpoints were assessed at Week 48.
About Islatravir (MK-8591) and Merck's HIV Research
Islatravir (MK-8591), Merck's investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI), blocks HIV-1 replication by multiple mechanisms including inhibition of reverse transcriptase translocation, resulting in immediate chain termination and induction of structural changes in the viral DNA. Islatravir is under evaluation in multiple ongoing early and late-stage clinical trials in combination with other antiretrovirals for potential daily and once-weekly treatments for HIV-1, with islatravir serving as the anchor medicine in the treatment regimens based on its potency and resistance profile.
In addition to the MK-8591A-053 trial, the MK-8591A-051 and MK-8591A-052 Phase 3 trials are evaluating a switch to DOR/ISL in adults with HIV-1 infection that is virologically suppressed on baseline antiretroviral therapy (NCT05631093) or BIC/FTC/TAF (NCT05630755). MK-8591A-054 (NCT05766501) is an open label study evaluating DOR/ISL (100 mg/0.25 mg) in individuals who participated in earlier Phase 3 trials of DOR/ISL (100 mg/0.75 mg). Islatravir in combination with Gilead's lenacapavir is in Phase 3 development as a novel oral once-weekly treatment for HIV-1 (NCT05052996), and islatravir in combination with our company's investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) ulonivirine (MK-8507) is in Phase 2b development (MK-8591B-060, NCT06891066) as an oral once-weekly treatment.
Merck's commitment to researching NRTTIs includes MK-8527, an investigational, novel oral, once-monthly NRTTI that is in Phase 3 development for HIV-1 pre-exposure prophylaxis (PrEP). The EXPrESSIVE-11 (MK-8527-011, NCT07044297) trial is evaluating the safety and efficacy of MK-8527 among people with greater likelihood of HIV-1 exposure in 16 countries, and in collaboration with the Gates Foundation, the EXPrESSIVE-10 (MK-8527-010, NCT07071623) trial is evaluating the safety and efficacy of MK-8527 in women and adolescent girls in sub-Saharan Africa; both trials are now enrolling.
For an overview of Merck's HIV treatment and prevention clinical development program, please click here.
Indications and usage for PIFELTRO® (doravirine) and DELSTRIGO® (doravirine, lamivudine, and tenofovir disoproxil fumarate) in the U.S.
PIFELTRO is indicated in combination with other antiretroviral (ARV) agents for the treatment of HIV-1 infection in adult patients with no prior ARV treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known substitutions associated with resistance to doravirine.
DELSTRIGO is indicated as a complete regimen for the treatment of HIV-1 infection in adult patients with no prior ARV treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known substitutions associated with resistance to the individual components of DELSTRIGO.
Full press release
https://www.merck.com/news/merck-announces-positive-topline-results-from-the-pivotal-phase-3-trial-evaluating-investigational-once-daily-oral-two-drug-single-tablet-regimen-of-doravirine-islatravir-dor-isl-in-treatment-na/
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