Week 96 results from the Phase III DRIVE-FORWARD clinical trial of doravirine in combination with other antiretroviral agents for treatment of HIV-1 infection in adult patients with no prior antiretroviral treatment history.- Merck Inc.

Merck Inc. has announced Week 96 results from the Phase III DRIVE-FORWARD clinical trial evaluating the efficacy and safety of doravirine (DOR), the company’s investigational non-nucleoside reverse transcriptase inhibitor (NNRTI), in combination with other antiretroviral agents, for the treatment of HIV-1 infection in adult patients with no prior antiretroviral treatment history (treatment-naïve).

At Week 96, 73.1 percent (277/379) of the group treated with once-daily DOR achieved viral suppression as measured by the proportion of patients who achieved HIV-1 RNA of less than 50 copies/mL, compared to 66.0 percent (248/376) of the group treated with once-daily ritonavir-boosted darunavir (DRV+r) (treatment difference: 7.1%, 95% confidence interval: 0.5, 13.7). These study results were presented as a late-breaking abstract at the 22nd International AIDS Conference (AIDS 2018) taking place July 23-27, 2018, in Amsterdam.

Previously, the findings at Week 48 demonstrated that once-daily DOR met its primary efficacy endpoint of non-inferiority compared to DRV+r, each in combination with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or abacavir/lamivudine (ABC/3TC). These data were presented at the Conference on Retroviruses and Opportunistic Infections in 2017.

In DRIVE-FORWARD, 766 participants (n=383 in each treatment group) with no antiretroviral treatment history were randomized and received either DOR (100 mg) once daily or DRV+r (800 mg and 100 mg, respectively) once daily, each in combination with FTC/TDF or ABC/3TC selected by the investigator. In this trial, after 96 weeks of treatment, the proportion of participants achieving HIV-1 RNA less than 50 copies/mL was 73.1 percent (277/379) in the DOR group and 66.0 percent (248/376) in the DRV+r group (treatment difference: 7.1%, 95% confidence interval: 0.5, 13.7). Results for participants with high baseline viral load (HIV-1 RNA greater than 100,000 copies/mL) were 65.4 percent (51/78) for DOR and 65.2 percent (43/66) for DRV+r (treatment difference: -1.1%, 95% confidence interval: -17.6, 15.3). In addition, the mean change from baseline in CD4+ T-cell count at 96 weeks was 224 cells/mm3 for DOR and 207 cells/mm3 for DRV+r (treatment difference: 17.4 cells/mm3, 95% confidence interval: -14.5, 49.3). In terms of resistance, two participants in the DOR treatment group (15 with successful genotype test) developed genotypic and phenotypic resistance to DOR through 96 weeks of treatment. The rate of discontinuation of therapy due to adverse events was 1.6 percent (6/383) in the DOR group and 3.4 percent (13/383) in the DRV+r group.

At Week 96 mean changes from baseline in fasting serum blood lipids for the DOR and DRV+r treated groups in levels of low density lipoprotein cholesterol (LDL-C) were DOR -0.4 mg/dL and DRV+r 14.0 mg/dL (treatment difference: -14.6, 95% confidence interval: -18.2, -11.0); and in levels of non-high density lipoprotein cholesterol (non-HDL-C) were DOR -0.5 mg/dL and DRV+r 17.7 mg/dL (treatment difference: -18.4, 95% confidence interval: -22.5, -14.3). Mean changes from baseline in total cholesterol, high density lipoprotein cholesterol (HDL-C), and triglycerides for the DOR-treated group and the DRV+r treated group were 4.1 mg/dL and 21.9 mg/dL (treatment difference: -18.1, 95% confidence interval: -22.5, -13.7), 4.5 mg/dL and 4.2 mg/dL (treatment difference: 0.4, 95% confidence interval: -1.3, 2.1), and -1.1 mg/dL and 22.5 mg/dL (treatment difference: -25.7, 95% confidence interval: -36.6, -14.7), respectively.