Investigational Doravirine Non-Inferior to Efavirenz for HIV-1 Infection

In a pivotal phase 3 clinical trial, the investigational drug doravirine demonstrated non-inferiority to efavirenz in adults with HIV-1. Merck plans to submit a New Drug Application in the fourth quarter of 2017, according to a press release.

DRIVE-AHEAD is an ongoing double-blind, multicenter, randomized, active comparator-controlled phase 3 study evaluating the safety and efficacy of a once-daily, single-tablet, fixed-dose doravirine combination versus the efavirenz combination regimen.

Doravirine is an investigational, non-nucleoside reverse transcriptase inhibitor, according to the release.

Included in the study were treatment-naïve adults with HIV-1. Participants were randomized to receive either the combination regimen containing 100 mg of doravirine, 300 mg of lamivudine, and 300 mg of tenofovir disoproxil fumarate (DOR/3TC/TDF) versus a combination containing 600 mg of efavirenz, 200 mg of emtricitabine, and 300 mg of tenofovir disoproxil fumarate (EFV/FTC/TDF).

The primary safety endpoint of DRIVE-AHEAD was the proportion of participants with neuropsychiatric adverse events (AEs) through week 48 categorized by dizziness, sleep disorders and disturbances, and inability to concentrate or think clearly.

At week 48, the results of the study showed that DOR/3TC/TDF met its primary efficacy endpoint of non-inferiority based on the proportion on patients achieving levels of HIV-1 RNA less than 50 copies/mL compared with EFV/FTC/TDF.

A statistically significant fewer number of patients in the DOR/3TC/TDF arm reported pre-specified categories of neuropsychiatric events compared with patients in the EFV/FTC/TDF arm. Additionally, the DOR/3TC/TDF regimen demonstrated a statistically lower change from baseline in fasting low-density lipoprotein cholesterol and non-high density lipoprotein cholesterol at week 48 compared with the EFV/FTC/TDF regimen.

“Data from DRIVE-AHEAD at 48 weeks show that a fixed-dose combination tablet containing doravirine achieved viral suppression in HIV-1 infected treatment-naïve adults, comparable to a fixed-dose combination containing efavirenz,” study investigator Dr Kathleen Squires said in the release. “The results for doravirine are encouraging, as it may offer appropriate patients a new single-tablet treatment option.”

At 48 weeks, the findings showed that 84% of patients in the treatment-naïve DOR/3TC/TDF arm achieved levels of HIV-1 RNA <50 copies/mL compared with 81% taking once-daily EFV/FTC/TDF.

Increases in mean CD4+ T cell counts from baseline favored DOR/3TC/TDF, with an estimated treatment difference of 10.1.

The investigators observed comparable efficacy across both treatment groups among patients with a high viral load at baseline, according to the report. Of the patients with a high viral load at baseline, 81% of the 69 patients in the DOR/3TC/TDF arm and 81% of the 73 patients in the EFV/FTC/TDF arm achieved the primary endpoint.

Regarding the primary safety endpoint, treatment with DOR/3TC/TDF resulted in fewer reports of pre-specified neuropsychiatric AEs compared with EFV/FTC/TDF.

Rates of drug-related AEs were lower among patients in the DOR/3TC/TDF arm versus the EFV/FTC/TDF arm. The most common AEs were headache, diarrhea, nasopharyngitis, dizziness, nausea, abnormal dreams, and rash.

“For more than 30 years, Merck has been at the forefront of HIV research and the development of new treatments that make a difference for people living with HIV,” Dr George Hanna, associate vice president of clinical research and Merck Research Laboratories, said in the release. “The development of doravirine is the result of a decade of Merck research. Based on our encouraging phase 3 study findings, we plan to file regulatory applications in Q4 2017.”

The findings were presented as part of a late-breaking oral session at the annual International Conference on HIV Science in Paris.