Merck has presented data from the dose-ranging portion of an ongoing phase IIb clinical trial of doravirine, the company’s investigational next-generation, non-nucleoside reverse transcriptase inhibitor (NNRTI). Interim data demonstrating potent antiretroviral (ARV) activity for four doses of once-daily, oral doravirine in combination with tenofovir/emtricitabine in treatment-naïve, HIV-1 infected adults after 24 weeks of treatment were presented during a late-breaker oral session. Based on these findings as well as other data from the doravirine clinical program, Merck plans to initiate a phase III clinical trial program for doravirine in combination with ARV therapy in the second half of 2014.
“Building on our long-standing commitment to the HIV community, Merck continues to evaluate new candidates we believe have the potential to make a meaningful difference in the lives of HIV patients,” said Daria Hazuda, Ph.D., vice president, Infectious Diseases, Merck Research Laboratories.
This randomized, double-blind clinical trial examined the safety, tolerability and efficacy of once-daily doravirine (25mg, 50mg, 100mg and 200mg) in combination with once-daily tenofovir/emtricitabine versus efavirenz (600mg), in treatment-naïve, HIV-1 infected patients. The primary efficacy analysis was percentage of patients achieving virologic response (< 40 copies/mL).
At 24 weeks, doravirine doses of 25mg, 50mg, 100mg, and 200mg showed virologic response rates consistent with those observed for efavirenz at a dose of 600mg. All treatment groups showed increased CD4 cell counts.
The incidence of drug-related adverse events was comparable among the doravirine-treated groups. The overall incidence of drug-related adverse events was lower in the doravirine-treated groups (n=166) than the efavirenz-treated group (n=42), 35% and 57%, respectively. The most common central nervous system (CNS) adverse events at week eight, the primary time point for evaluation of CNS adverse experiences, were dizziness [3% doravirine (overall) and 23.8% efavirenz], nightmare [1.2% doravirine (overall) and 9.5% efavirenz], abnormal dreams [9% doravirine (overall) and 7.1% efavirenz], and insomnia [5.4% doravirine (overall) and 7.1% efavirenz].
Based on the 24-week data from this dose-finding study, a single dose of 100mg doravirine was chosen to be studied for the remainder of this study, up to 96 weeks.