Analyses Add Support for Further Investigation of Islatravir in Combination with Doravirine for Certain Patients

Post-hoc Weight Analyses from DRIVE-SHIFT Trial of DELSTRIGO™ (doravirine/lamivudine/tenofovir disoproxil fumarate) Also Announced

KENILWORTH, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced new analyses from the Phase 2b trial (NCT03272347) evaluating the safety and efficacy of islatravir, the company’s investigational oral nucleoside reverse transcriptase translocation inhibitor (NRTTI), in combination with doravirine (PIFELTRO™), in adults with HIV-1 infection who had not previously received antiretroviral treatment. The first sub-analysis further characterized the tolerability and safety profile of islatravir in combination with doravirine (100 mg) through Week 48 across the three dose levels studied (0.25, 0.75, 2.25 mg). The second sub-analysis demonstrated that participants who initiated treatment with islatravir and doravirine in combination with 3TC and switched to islatravir and doravirine maintained antiviral activity at Week 48 as measured by HIV-1 RNA 10% participants) in the DELSTRIGO-treated group were diarrhea (16.1%), bronchitis (12.9%) and syphilis (12.9%). The most common reported adverse events (reported by >10% participants) in the islatravir-treated groups were: 0.25 mg (sinusitis, pain in extremity, headache - 10.3%, 10.3% and 13.8%, respectively); 0.75 mg (diarrhea, nausea, bronchitis, nasopharyngitis, syphilis, vitamin D deficiency -13.3%, 13.3%, 13.3%, 13.3%, 10.0%, 13.3%, respectively); 2.25 mg (arthralgia, headache - 12.9%, 12.9%, respectively). The majority of all adverse events were mild and did not result in study discontinuation. Two participants in the islatravir-treated dose groups (both 2.25 mg) discontinued due to an AE. One participant in the DELSTRIGO group discontinued due to a serious AE considered to be drug related.

In the study, PDVF was defined as viral rebound (HIV-1 RNA ≥50 copies/mL after initial response at any time during the study or confirmed HIV-1 RNA >1 log increase from the lowest HIV-1 RNA level after a >1 log decrease in HIV-1 RNA from baseline, at any time during the study) or non-response (≥200 copies/mL at any time from Week 24 through Week 48 and confirmed HIV-1 RNA ≥50 copies/mL at Week 48); PDVF had to be confirmed by an additional HIV-1 RNA measurement within two weeks. At Week 48, rates of PDVF were low and all participants who discontinued due to PDVF had levels of HIV-1 RNA below the clinically significant level of 200 copies/mL. The observed low-level viremia was comparable to levels detected in other studies of previously untreated patients. At Week 48, 89.7% (26/29), 90.0% (27/30) and 77.4% (24/31) of randomized participants achieved HIV-1 RNA