Merck, known as MSD outside of the United States and Canada, announced the release of positive results from two pivotal Phase 3 trials of the investigational, once-daily, oral, two-drug regimen of doravirine/islatravir [DOR/ISL (100mg/0.25mg)] in adults with HIV-1 infection that is virologically suppressed on bictegravir/emtricitabine/tenofovir alafenamidei [BIC/FTC/TAF (50mg/200mg/25mg)] in trial MK-8591A-052) or antiretrovir At Week 48 in both studies, DOR/ISL fulfilled the primary efficacy success criterion for non-inferiority to comparator antiretroviral treatments as well as the primary safety objectives.
The findings will be presented as late-breaking oral presentations at the 32nd Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco, as well as during a press conference. Merck intends to start submitting applications for marketing authorization to regulatory bodies in mid-2025.
In the double-blind experiment MK-8591A-052 (Abstract #204A), the primary endpoint (HIV-1 RNA ≥50 copies/mL) indicated that 1.5% of patients who transitioned to DOR/ISL had a viral load of ≥50 copies/mL at Week 48, compared to 0.6% on BIC/FTC/TAF (treatment difference 0.9%, 95% CI -1.9, 2.9). At Week 48, 91.5% of patients moved to DOR/ISL maintained viral suppression (HIV-1 RNA <50 copies/mL), whereas 94.2% kept receiving BIC/FTC/TAF (treatment difference -2.6%, 95% CI -7.1, 2.6; secondary objective).
In the open-label trial MK-8591A-051 (Abstract #204B), the primary endpoint (HIV-1 RNA ≥50 copies/mL) indicated 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 bART (treatment difference -3.6%, 95% CI -7.8, -0.8). At Week 48, 95.6% of patients who converted to DOR/ISL maintained viral suppression (HIV-1 RNA <50 copies/mL), compared to 91.9% who continued on bART (treatment difference 3.7%, 95% CI -0.3, 8.9; secondary objective).
In all studies, the safety profile of DOR/ISL was broadly equivalent to the comparative antiretroviral regimens, including BIC/FTC/TAF in MK-8591A-052. At week 48, the mean percent change in total lymphocyte and CD4 counts was similar across the DOR/ISL and comparator regimen. There was no treatment-emergent resistance to DOR or ISL in either trial.
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.
Professor Chloe Orkin, Dean for Healthcare Transformation, Queen Mary University of London, United Kingdom
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Islatravir, Merck’s investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI), inhibits HIV-1 replication through a variety of mechanisms, including inhibition of reverse transcriptase translocation, which results in immediate chain termination, and delayed chain termination due to structural changes induced in viral DNA.
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 3 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.
Dr. Eliav Barr
Source: Merck
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