Next-Generation HIV Drug Has Low Adverse Event Incidence

An investigational HIV drug developed by Merck exhibited a strong overall safety and efficacy profile in a recently completed phase 2b study.

The trial compared the next-generation, once-daily oral drug, doravirine, plus tenofovir/emtricitabine (TDF/FTC) to efavirenz plus TDF/FTC in previously untreated patients with HIV-1 infection. In the study, doravirine exhibited significantly lower incidence of 1 or more central nervous system adverse events versus efavirenz.

“We are encouraged by the antiviral activity and the overall tolerability profile of doravirine and look forward to initiating phase 3 studies,” said Hedy Teppler, MD, executive director of Infectious Diseases at Merck Research Laboratories, in a press release.

In the first stage of the randomized, double blind, dose-ranging clinical trial, 166 patients received a once-daily doravirine dose of either 25 mg, 50 mg, 100 mg, or 200 mg dose, while 42 patients received efavirenz 600 mg, both in combination with TDF/FTC.

Following the dose selection phase, all doravirine-treated patients switched to 100 mg of doravirine for the expansion phase of the study. In that expansion phase, an additional 132 patients received 100 mg doravirine, while 66 patients received efavirenz, both in combination with TDF/FTC.

Follow-up data through 48 weeks of treatment showed a 76% overall virologic response rate across all 4 doravirine dosage amounts, compared with 71% for those given efavirenz. Additionally, all treatment groups exhibited an increased CD4 cell count relative to baseline.

The 166 patients who received doravirine also showed lower overall incidence of adverse events (36.7%) compared with the 42 patients who received efavirenz (57.1%).

The most common drug-related adverse events reported in both the doravirine and efavirenz groups were abnormal dreams, nausea, fatigue, diarrhea, and dizziness. However, patients in the doravirine group exhibited lower incidence of laboratory abnormalities in routine clinical tests, including increased total cholesterol and low-density lipoprotein cholesterol.

A phase 3 clinical trial of doravirine is expected to begin enrollment by the end of 2014. The study will evaluate treatment-naïve patients to compare the efficacy, safety, and tolerability of doravirine and ritonavir-boosted darunavir in combination with other antiretroviral therapies.