Merck & Co (MSD) is looking to file for approval of its human immunodeficiency virus (HIV) treatment after two positive Phase III trial readouts.
Its once-daily oral combination of the approved drug Pifeltro (doravirine) and its investigational therapy islatravir (DOR/ISL), maintained HIV-1 viral suppression after 48 weeks in two pivotal trials.
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A double-blind study investigated the therapy in adult patients with HIV-1 infection suppressed on Gilead’s Biktarvy (bictegravir/emtricitabine/tenofovir alafenamidei). Meanwhile, an open-label trial enrolled patients on background antiretroviral (bART) therapy. Both studies met the primary efficacy endpoint of non-inferiority to comparator antiretroviral therapies and the primary safety endpoint.
In the double-blind trial (NCT05630755) in patients on Biktarvy, 1.5% of patients who switched to DOR/ISL had a viral load of more than or equal to 50 copies/mL compared to 0.6% for those who remained on Biktarvy.
Also at week 48, 91.5% of patients who switched to DOR/ISL maintained viral suppression compared to 94.2% of participants who continued receiving Biktarvy. While MSD’s therapy did not outperform Gilead’s for viral suppression, the study met the bar (4% margin) for non-inferiority.
In the open-label trial (NCT05631093) in patients on bART, 1.4% of patients who received DOR/ISL had a viral load of more than or equal to 50 copies/mL compared to 4.9% on bART. After 48 weeks, 95.6% of patients who switched to DOR/ISL maintained viral suppression compared to 91.9% of patients who continued bART.
Across both trials, the safety profile of DOR/ISL was generally comparable to the comparator antiretroviral regimens. The mean per cent change in total lymphocyte and CD4 counts were similar for DOR/ISL and comparator regimens, a previous adverse event that caused the islatravir programme to be affected with a clinical hold by the US Food and Drug Administration (FDA) in 2021.
As a result of this data, which was also presented at the Conference on Retroviruses and Opportunistic Infections (CROI) 2025, MSD plans to submit applications for marketing authorisation by mid-2025.
Merck Research Laboratories’ chief medical officer and global clinical development head Dr Eliav Barr said: “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.”
Pifeltro is a non-nucleoside reverse transcriptase inhibitor (NNRTI), which interferes with reverse transcriptase to prevent the HIV from multiplying. Meanwhile, Islatravir is a reverse transcriptase inhibitor that causes premature termination of DNA transcription leading to decreased cell division of the virus. It also acts as a non-obligate chain terminator.
More HIV success at CROI
Also at CROI, Gilead reported it was accelerating its once-yearly lenacapavir pre-exposure prophylaxis (PrEP) injection to Phase III trials following a positive Phase I readout. Gilead is currently awaiting a regulatory decision on its twice-yearly lenacapavir PrEP, which has been hailed a ‘miracle drug’.
In October 2024, Gilead and MSD announced that their once-weekly HIV treatment, a combination of islatravir and Gilead’s Sulenca (lenacapavir), would be advancing to Phase III trials. The companies partnered to develop long-acting HIV treatments in March 2021.
