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Merck Announces Data from 48-Week Phase 2b Study of Investigational HIV Therapy Doravirine (MK-1439) in Treatment-Naive Patients
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Phase 3 Clinical Trial Enrollment Scheduled to Start by the End of 2014
Monday, November 3, 2014 5:00 am EST
WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the presentation of results from a Phase 2b clinical trial evaluating the safety and efficacy of once-daily oral doravirine, an investigational next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI), plus tenofovir/emtricitabine (TDF/FTC) compared to efavirenz plus TDF/FTC in previously untreated patients with HIV-1 infection. Results were presented as a poster (#0434) and oral presentation by Dr. Josep M. Gatell, head, Infectious Diseases and AIDS Units-IDIBAPS, Hospital Clinic, Barcelona, at the 12th International Congress on HIV Drug Therapy being held in Glasgow, United Kingdom, Nov. 2-6.
The primary safety analysis from the expansion phase of the study compared the incidence of central nervous system (CNS) adverse events (AEs) by Week 8 in patients who received doravirine 100 mg plus TDF/FTC (n=108) versus patients who received efavirenz with TDF/FTC (n=108). The results showed a significantly lower incidence of one or more of reported CNS AEs (all causality) among the doravirine-treated group compared to the efavirenz-treated group (22.2 % vs. 43.5 %, respectively; p<0.001). The most common (occurring in more than 5 percent of patients) CNS AEs in the doravirine-and efavirenz-treated groups, respectively, were dizziness (9.3 % vs. 27.8 %), insomnia (6.5 % vs. 2.8 %), abnormal dreams (5.6 % vs. 16.7 %) and nightmares (5.6 % vs. 8.3 %).
Interim results for this ongoing Phase 2b study, including the primary efficacy analysis for dose selection based on 24-week data from the dose-ranging cohort of the study, were previously presented at the 21st Conference on Retroviruses and Opportunistic Infections (CROI) in March 2014.
"This program underscores Merck's ongoing commitment to the research and development of new therapeutic options for patients with HIV," said Dr. Hedy Teppler, executive director, Infectious Diseases, Merck Research Laboratories. "We are encouraged by the antiviral activity and the overall tolerability profile of doravirine and look forward to initiating Phase 3 studies."
Additional follow-up data through 48 weeks of treatment showed a 76 percent (n=126/166) overall virologic response rate (HIV RNA <40 c/ml) for all doravirine doses (25, 50, 100 and 200 mg) that is comparable to 71 percent (n=30/42) reported for patients administered efavirenz (600 mg). In addition, all treatment groups showed increased CD4 cell counts relative to baseline, consistent with the 24-week findings.
After 48 weeks of treatment, patients in the dose ranging part of the study who received doravirine demonstrated a lower overall incidence of drug-related adverse events (36.7%; n=166) than those who received efavirenz (57.1%; n=42).
The most commonly reported drug-related clinical adverse events in the doravirine and efavirenz groups respectively were abnormal dreams (10.2% vs. 9.5%); nausea (7.8% vs. 2.4%); fatigue (7.2% vs. 4.8%); diarrhea (4.8% vs. 9.5%) and dizziness (3.0% vs. 23.8%). Doravirine-treated patients also had a lower incidence of laboratory abnormalities in routine clinical tests including increased total cholesterol (6.8% for doravirine vs. 31.6% for efavirenz) and LDL cholesterol (6.3% for doravirine vs. 18.4% for efavirenz).
Merck plans to initiate the first Phase 3 clinical trial of doravirine by the end of 2014, NCT02275780. The study will enroll treatment-na•ve patients and compare the efficacy, safety and tolerability of doravirine and ritonavir-boosted darunavir, both in combination with other anti-retroviral therapy.
About the Phase 2b Study
The Phase 2b randomized, double blind, dose-ranging clinical trial (NCT01632345) evaluated the efficacy, safety and tolerability of once-daily doravirine (25, 50, 100 and 200 mg) compared to once-daily efavirenz 600 mg, both in combination with TDF/FTC, in previously untreated HIV-1 infected patients. The study has two parts:
· In Part 1, the dose-ranging phase, patients received once daily doravirine (N=166) at one of four doses (25, 50, 100 or 200 mg) or efavirenz (n=42), both in combination with TDF/FTC. The doravirine dose to be used in Part 2 of the Phase 2b study and in Phase 3 was selected based on the Week 24 safety and efficacy data in doravirine-treated patients. After dose selection, all doravirine-treated patients were switched to the selected dose (100 mg doravirine) for the expansion phase of the study.
· In Part 2, the expansion phase, an additional 132 patients were enrolled to receive 100 mg doravirine (n=66) or efavirenz (n=66), both in combination with TDF/FTC, to enable an assessment of the CNS safety and tolerability profile of doravirine.
The planned total treatment duration in the Phase 2 study is 96 weeks.
About Doravirine
Doravirine, also known as MK-1439, is an investigational next-generation, NNRTI being developed by Merck for the treatment of HIV-1 infection. In preclinical studies, doravirine showed potent antiviral activity against HIV-1. In early clinical studies, doravirine demonstrated a pharmacokinetic profile supportive of a once-daily dosing schedule and did not show a significant food effect.
Merck's Commitment to HIV
For more than 25 years, Merck has been at the forefront of the response to the HIV epidemic, and has helped to make a difference through our proud legacy of commitment to innovation, collaboration with the community, and expanding global access to medicines. Merck is dedicated to applying our scientific expertise, resources and global reach to deliver healthcare solutions that support people living with HIV worldwide.
About Merck
Today's Merck is a global healthcare 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 healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook and YouTube.
Forward-Looking Statement
This news release includes "forward-looking statements" within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of Merck'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; Merck'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 Merck's patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.
Merck 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 Merck's 2013 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).
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