Doravirine/Islatravir Regimen Shows Promise in Multiple Phase III Trials for the Treatment of HIV

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Merck has announced positive results from two Phase III clinical trials of the investigational regimen of doravirine/islatravir (DOR/ISL) in adults with HIV-1 that is virologically suppressed on Gilead’s Biktarvy [bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF)] or antiretroviral therapy. In both studies, the DOR/ISL combination met the primary efficacy success criterion for non-inferiority to comparator antiretroviral therapies at week 48.¹

In the double-blind trial evaluating DOR/ISL in patients with virological suppression on BIC/FTC/TAF, MK-8591A-052, 1.5% who switched to DOR/ISL had a viral load of ≥50 copies/mL at week 48, compared to 0.6% on just BIC/FTC/TAF, meeting the primary endpoint. Additionally, the secondary endpoint was met with 91.5% of participants who switched to DOR/ISL maintaining viral suppression compared to 94.2% of participants who continued receiving BIC/FTC/TAF.

In a press release, Professor Chloe Orkin, dean for healthcare transformation, Queen Mary University of London, United Kingdom, said, “Despite the availability of multiple daily antiretroviral therapies, the needs of people living with HIV are evolving. Many people living with HIV are older and also managing comorbidities, making it important to have daily treatment options that can help meet each person’s unique health needs. I’m excited to see that DOR/ISL has potential as a new daily treatment option for people living with HIV who may benefit from this two-drug regimen.”

The DOR/ISL combination also saw success in the open-label study MK-8591A-051, which showed that 1.4% of patients who received DOR/ISL had a viral load of ≥50 copies/mL at week 48, compared to 4.9% on baseline antiretroviral therapy. Similar to the results of the previously mentioned trial, 95.6% of participants who switched to DOR/ISL maintained viral suppression compared to 91.9% of participants who continued antiretroviral therapy. Once again, both primary and secondary endpoints were met.

In the same press release, Eliav Barr, MD, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories, added, “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. 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.”

With two Phase III wins now under its belt for DOR/ISL, Merck plans to begin submitting applications for marketing authorization to regulatory agencies by the middle of this year.

The FDA approved doravirine for the treatment of HIV-1 in adults who have not taken HIV-1 medicines before as Pifeltro in August 2018. The approval was based primarily on the results from two different trials of 1,494 adults with the infection. The efficacy of Pifletro was assessed after 48 weeks by comparing it to other medicines.²

In September 2019, Merck announced the FDA approved supplemental New Drug Applications for Pifeltro (in combination with other antiretroviral agents) along with Delstrigo (as a complete regimen), expanding their indications to include adult patients with HIV-1 infection who are virologically suppressed on a stable antiretroviral regimen. These approvals were made based on results from Merck’s Phase III DRIVE-SHIFT trial.³

References

1. 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. News release. Merck. March 12, 2025. Accessed March 13, 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/

2. Drug Trials Snapshots: PIFELTRO. FDA. Accessed March 13, 2025. https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-pifeltro

3. Merck’s PIFELTRO™ (doravirine) and DELSTRIGO™ (doravirine/lamivudine/tenofovir disoproxil fumarate) Receive US FDA Approval for Use in Appropriate Adults Living with HIV-1 Who Are Virologically Suppressed. News release. Merck. September 20, 2019. Accessed March 13, 2025. https://www.merck.com/news/mercks-pifeltro-doravirine-and-delstrigo-doravirine-lamivudine-tenofovir-disoproxil-fumarate-receive-us-fda-approval-for-use-in-appropriate-adults-living-with-hiv-1-who/#:~:text=PIFELTRO%20and%20DELSTRIGO%20were%20approved,no%20prior%20antiretroviral%20treatment%20history.