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.
Go deeper with GlobalData
Discover B2B Marketing That Performs
Combine business intelligence and editorial excellence to reach engaged professionals across 36 leading media platforms.
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.
US Tariffs are shifting - will you react or anticipate?
Don’t let policy changes catch you off guard. Stay proactive with real-time data and expert analysis.
By GlobalDataAcross 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.
