Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has accepted for review two New Drug Applications (NDAs) for doravirine, the company’s investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of HIV-1 infection in adults. The NDAs include data for doravirine (DOR) as a once-daily tablet for use in combination with other antiretroviral agents, and for use of doravirine with lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) in a once-daily fixed-dose combination single tablet as a complete regimen (DOR/3TC/TDF). The FDA has set a target action date of Oct. 23, 2018, for both applications under the Prescription Drug User Fee Act (PDUFA).

“Since the earliest days of the epidemic, Merck has sustained our commitment to research and meeting the needs of people living with HIV. Doravirine was engineered by our research team to provide a meaningful new treatment approach and address unmet medical needs in the treatment of HIV-1 infection,” said Dr. George Hanna, associate vice president, global clinical development, Merck Research Laboratories. “We have been pleased with the clinical findings to date and look forward to working with the FDA as it reviews our applications."

The NDAs are based upon the findings at Week 48 of two ongoing Phase 3 trials, DRIVE-FORWARD and DRIVE-AHEAD, evaluating the efficacy and safety of doravirine and the fixed-dose combination regimen of DOR/3TC/TDF, respectively. These data were previously presented at CROI-2017 and IAS 2017, respectively.

About Doravirine

Doravirine (MK-1439, DOR) is an investigational NNRTI being evaluated by Merck for the treatment of HIV-1 infection. DOR is being evaluated in several ongoing clinical trials both as a once-daily single-entity tablet in combination with other antiretroviral agents in a tailored regimen, and as a once-daily fixed-dose combination (DOR/3TC/TDF) in a complete single tablet regimen. Phase 3 trials include DRIVE-FORWARD, a trial comparing DOR to once-daily ritonavir-boosted darunavir (DRV+r), each administered in combination with FTC/TDF or abacavir (ABC)/3TC, in treatment-naïve adults; DRIVE-AHEAD, a trial comparing DOR/3TC/TDF to EFV/FTC/TDF in treatment-naïve adults; and DRIVE-SHIFT, a trial evaluating a switch to DOR/3TC/TDF in HIV-1 infected adults who are currently virologically suppressed on another antiretroviral regimen. Other ongoing Phase 2 clinical trials include an evaluation of DOR/3TC/TDF in treatment-naïve adults with transmitted resistance to NNRTIs and in individuals switching from EFV due to intolerability.

About DRIVE-FORWARD

DRIVE-FORWARD is a multicenter, double-blind, randomized non-inferiority trial in which 769 treatment-naïve adults with HIV-1 infection received either DOR (100 mg) or DRV+r (800 mg +100 mg), both administered orally once-daily in combination with either TDF/FTC or ABC/3TC. The primary endpoint of the clinical trial was the proportion of participants with HIV-1 RNA less than 50 copies/mL at Week 48. Secondary endpoints included an evaluation of the effects of DOR and DRV+r on fasting serum lipids, change from baseline in CD4+ T-cell count, and evaluation of safety and tolerability. The trial consists of a 96-week double-blind treatment period (base study) and an open label extension after participants complete the base study. For further information regarding DRIVE-FORWARD please visit www.clinicaltrials.gov clinical trial registry number NCT02275780.

About DRIVE-AHEAD

DRIVE-AHEAD is an ongoing Phase 3 multicenter, double-blind, randomized, active comparator-controlled clinical trial evaluating the safety and efficacy of a once-daily, single-tablet, fixed-dose combination consisting of DOR/3TC/TDF (100mg/300mg/300mg) versus a once daily, single-tablet, fixed-dose combination of EFV/FTC/TDF (600mg/200mg/300mg) in treatment-naïve HIV-1 infected adults. The primary endpoint of the clinical trial was the proportion of participants with HIV-1 RNA less than 50 copies/mL at Week 48. The primary safety endpoint was the proportion of participants with neuropsychiatric adverse events through Week 48 in the following pre-specified categories: dizziness, sleep disorders and disturbances, and the inability to think clearly or concentrate. Secondary endpoints included an evaluation of the effects of DOR/3TC/TDF and EFV/FTC/TDF on fasting serum lipids, change from baseline in CD4+ T-cell count, and evaluation of safety and tolerability. The trial consists of a 96-week double-blind treatment period (base study) and an open label extension after participants complete the base study. For further information regarding DRIVE-AHEAD please visit www.clinicaltrials.gov clinical trial registry number NCT02403674.