FDA accepts Merck’s NDA for doravirine/islatravir to treat suppressed HIV-1

FDA accepts Merck’s NDA for doravirine/islatravir to treat suppressed HIV-1

By, Admin 11 July 2025

Overview

Merck, known as MSD outside of the United States and Canada, announced that the US Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for doravirine/islatravir (DOR/ISL), an investigational, once-daily, oral, two-drug regimen for adults with HIV-1 infection that is virologically suppressed on antiretroviral therapy. The FDA has set a target action date of April 28, 2026, for the application under the Prescription Drug User Fee Act (PDUFA).

Statement from Dr. Eliav Barr: Merck Research Laboratories

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 Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. 
“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.”

Study behind this NDA

  • The NDA is based on findings at Week 48 of two pivotal phase 3 clinical trials (MK-8591A-051 and MK-8591A-052) where DOR/ISL was demonstrated to be non-inferior to baseline antiretroviral therapy (bART) in the open-label trial MK-8591A-051 and non-inferior to bictegravir/emtrictabine/tenofovir alafenamidei [BIC/FTC/TAF (50mg/200mg/25mg)] in the double-blind trial MK-8591A-052. 
  • Across both trials, the safety profile of DOR/ISL was generally comparable to comparator baseline antiretroviral regimens in trial MK-8591A-051 and BIC/FTC/TAF in trial MK-8591A-052. 
  • Data from these trials were presented during the 2025 Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco.

About MK-8591A-051 trial

  • MK-8591A-051 is a phase 3, open-label, randomized, active-controlled clinical trial evaluating the efficacy and safety of a switch to investigational, oral, once-daily DOR/ISL (100mg/0.25mg) in adults with HIV-1 infection that has been virologically suppressed using ART. 
  • The primary efficacy endpoint was the percentage of participants with HIV-1 RNA =50 copies/mL at Week 48 (non-inferiority margin 4%). 
  • In this trial, 551 adults with HIV-1 RNA <50 copies/mL for three months or more on oral 2- or 3-drug ART, with no history of treatment failure and no known virologic resistance to DOR, were randomized 2:1 and switched to DOR/ISL (n=366) or continued bART (n=185), stratified by bART regimen. 
  • The median age of participants was 51 years; 39.7% were assigned female sex at birth, 45.4% were Black or African American, and 14.5% were Hispanic or Latine. 
  • At baseline, 64.2% were treated with an InSTI-based regimen, 30.3% with an NNRTI-based regimen, and 5.4% with a protease inhibitor (PI)-based regimen, with median duration on current ART of 3.8 years (IQR 2.0-6.3).

About MK-8591A-052 trial

  • MK-8591A-052 is a phase 3, double-blind, randomized, active-controlled clinical trial to evaluate the efficacy and safety of a switch to investigational, oral, once-daily DOR/ISL (100mg/0.25mg) in adults with HIV-1 infection that has been virologically suppressed on BIC/FTC/TAF (50mg/200mg/25mg). 
  • The primary efficacy endpoint was the percentage of participants with HIV-1 RNA =50 copies/mL at Week 48 (non-inferiority margin 4%). 
  • In this trial, 513 adults with HIV-1 who had virologic suppression for three months or more on BIC/FTC/TAF, no history of treatment failure and no known resistance to DOR were randomized (2:1) and switched to DOR/ISL (n=342) or continued treatment with BIC/FTC/TAF (n=171). 
  • The median age of participants was 47 years; 21.4% were assigned female sex at birth, 30.8% were Black or African American, and 22.8% were Hispanic or Latine. 
  • The median duration of BIC/FTC/TAF treatment prior to trial enrollment was 3.4 years (IQR 2.0-5.0).

About the drug: Islatravir (MK-8591)

  • 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, resulting in delayed chain termination. 
  • 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-051 and MK-8591A-052 trials, ongoing phase 3 trials of daily DOR/ISL (100mg /0.25mg) include MK-8591A-053 in people with HIV who had not previously received treatment (treatment-naïve), and MK-8591A-054 evaluating open-label 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, and islatravir in combination with our company’s investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) ulonivirine (MK-8507) is in phase 2 development as an oral once-weekly treatment.

Merck’s commitment to researching NRTTIs includes MK-8527, an investigational, novel oral, once-monthly NRTTI candidate that is in phase 2 development for HIV-1 pre-exposure prophylaxis (PrEP).

Pifeltro’s indication

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’s indication

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.

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