KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), 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 from Feb. 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. “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 and DRV+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.”
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 either TDF/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.gov clinical trial registry number NCT02275780.
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.
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 on Twitter, Facebook, YouTube and LinkedIn.
Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA
This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.
Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.
The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s 2015 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).