Merck's Doravirine, An Investigational Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) For The Treatment Of HIV-1 Infection, Met Primary Efficacy Endpoint I n Pivotal Phase 3 Trial

Merck, known as MSD outside the United States and Canada, today announced results of a pivotal Phase 3 clinical trial evaluating the safety and efficacy of doravirine (MK-1439), an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI).  The study met its primary efficacy endpoint of the proportion of participants achieving levels of HIV-1RNA less than 50 copies/mL after 48 weeks of treatment, demonstrating the non-inferiority of once-daily doravirine (DOR) to once-daily ritonavir-boosted darunavir (DRV+r), each administered with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) or abacavir/lamivudine (ABC/3TC), in previously untreated (treatment naïve) adults with HIV-1 infection.  In addition, a secondary endpoint showed that the DOR-treated group had statistically significant lower levels of fasting low density lipoprotein cholesterol (LDL-C), versus the DRV+r group.  Findings from the ongoing “DRIVE-FORWARD” Phase 3 trial following 48 weeks of treatment were presented as a late-breaking abstract at the annual Conference on Retroviruses and Opportunistic Infections (CROI) being held in Seattle, WA, from February 13-16, 2017.

“Improved understanding of the biology of HIV and growing clinical evidence from current therapies are advancing the management of HIV infection,” said Dr. Kathleen Squires, professor and director of infectious diseases, Thomas Jefferson University, Philadelphia, PA.  “The results of this study provide solid evidence of the efficacy and safety profile of doravirine as a potential treatment option for treatment-naïve HIV-1 patients.”

Data from DRIVE- FORWARD

In the trial, after 48 weeks of treatment, the proportion of participants achieving levels of HIV-1 RNA less than 50 copies/mL following once-daily DOR (100 mg) or once-daily

DRV+r (800 mg and 100 mg respectively), each in combination with either TDF/FTC or ABC/3TC, was 83.8 percent (321/383) and 79.9 percent (306/383), respectively; with a treatment difference (95 % confidence interval) of  3.9  [-1.6, 9.4].  Increases in mean CD4+ T-cell counts from baseline were similar for the DOR and DRV+r treatment groups:  193 and 186 cells/mm3, respectively.

In addition, comparable efficacy was observed for participants with baseline levels of HIV-1 RNA greater than 100,000 copies/mL:  81.0 percent (64/79) for DOR and 76.4 percent (55/72) for DRV+r; with a treatment difference (95% confidence interval) of 3.0 [-11.2, 17.1].  One out of 383 participants developed phenotypic and genotypic resistance in the DOR arm (the patient came off study at Week 24 because of non-adherence).  None of the 383 participants receiving DRV+r developed phenotypic and genotypic resistance.

The rates of reported adverse drug reactions were 31 percent (117/383) for DOR and 32 percent (123/383) for DRV+r.  Discontinuations due to adverse events for the DOR andDRV+r treatment groups were 2 percent (6/383) and 3 percent (12/383), respectively.  The most common adverse events for DOR and DRV+r (occurring in greater than or equal to 10 percent of participants) were:  diarrhea (14% vs. 22%); headache (14% vs. 11%); nausea (11% vs. 12%) and nasopharyngitis (8% vs. 10 %), respectively.

Analysis of fasting serum blood lipids for the DOR and DRV+r treated groups showed a statistically significant difference (p<0.0001) in mean changes from baseline in the levels of LDL-C (-4.5 mg/dL vs. +9.9 mg/dL) and non-high density lipoprotein cholesterol (non-HDL-C)

(-5.3 mg/dL vs. +13.8 mg/dL), respectively.  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 -1.4 mg/dL, +3.9 mg/dL, and -3.1 mg/dL vs. +17.9 mg/dL, +4.2 mg/dL, and +22 mg/dL, respectively.

“Merck has been at the forefront of research into HIV for three decades,” said Dr. George Hanna, associate vice president, clinical research, Merck Research Laboratories. “We are encouraged by these results, which provide additional insights into the efficacy and safety of doravirine.”           

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 100 mg doravirine or 800 mg darunavir plus 100 mg ritonavir, both administered orally once-daily in combination with eitherTDF/FTC or ABC/3TC.  The primary endpoint of the clinical trial was the proportion of participants with HIV-1 RNA copies of less than 50 copies/mL at Week 48.  There were a number of secondary endpoints, including 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.

For further information regarding DRIVE-FORWARD please visit www.clinicaltrials.govclinical trial registry number NCT02275780.     

About Doravirine
Doravirine is an investigational NNRTI being evaluated by Merck for the treatment of HIV-1 infection.  In early clinical studies, doravirine demonstrated a pharmacokinetic profile supportive of once-daily dosing and the ability to be dosed with or without food.

 Doravirine is also being evaluated in several ongoing studies as a fixed dose single tablet regimen with 3TC and TDF (DOR/3TC/TDF).  Phase 2 studies include an evaluation of DOR/3TC/TDF in treatment-naïve participants with transmitted resistance to NNRTIs and in people switching from efavirenz due to intolerability. Phase 3 studies include DRIVE-AHEAD, a trial comparing DOR/3TC/TDF to efavirenz/ FTC/TDF in treatment-naïve participants, and DRIVE-SHIFT, a trial evaluating a switch to DOR/3TC/TDF in people who are currently virologically suppressed on another antiretroviral regimen.

About Merck
For over a century, Merck has been a global health care leader working to help the world be well.  Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs, and partnerships. For more information, visit www.merck.com and connect with us onTwitter, Facebook, YouTube and LinkedIn.