KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the presentation of results from the company's Phase 3 C-EDGE CO-STAR clinical trial evaluating the efficacy and safety of the investigational once-daily tablet elbasvir/grazoprevir1 (50mg/100mg) in patients with chronic hepatitis C virus (HCV) genotypes (GT) 1, 4 or 6 infection who inject drugs and are receiving opioid agonist therapy (OAT). Ninety-five percent (189/198) of patients treated with elbasvir/grazoprevir for 12 weeks in the pre-specified primary efficacy analysis population achieved sustained virologic response 12 weeks after the completion of treatment (SVR12, considered virologic cure). Adherence to treatment was high, with 97 percent of patients taking at least 95 percent of their study medication over the 12 weeks of therapy. These findings will be featured today at the American Association for the Study of Liver Diseases' President's Press Conference at The Liver Meeting® and presented in an oral session on Sunday, November 15 (Abstract #40).
"Injection drug use is a major factor fueling the global hepatitis C crisis, yet people with chronic hepatitis C virus infection who inject drugs often remain overlooked and underserved," said Dr. Ronald Nahass, president, ID CARE, New Jersey. "Patients in this study with chronic hepatitis C virus infection on opioid agonist therapy, including many who continued to use drugs during the trial, were able to complete treatment with elbasvir/grazoprevir and achieve high virologic cure rates."
C-EDGE CO-STAR is a Phase 3 randomized, double-blind, placebo-controlled study evaluating treatment with elbasvir/grazoprevir in patients with chronic HCV GT1, 4 or 6 infection who are on OAT (e.g., methadone, buprenorphine). The study randomized 301 patients to one of two study arms: an immediate treatment group (ITG) that received elbasvir/grazoprevir (blinded) for 12 weeks (n=201), and a deferred treatment group (DTG) that received 12 weeks of placebo (control arm) followed by a four-week follow-up period and then elbasvir/grazoprevir (open-label) for 12 weeks (n=100).
The primary efficacy analysis – or modified full analysis set (mFAS) – excluded patients who discontinued treatment for reasons unrelated to study drug (n=3) and classified patients who had cleared their baseline infection but subsequently acquired a new infection as treatment successes (n=5). In the mFAS, 96 percent of GT1a patients (147/153), 97 percent of GT1b patients (28/29), 100 percent of GT4 patients (11/11) and 60 percent of GT6 patients (3/5) achieved virologic cure when treated with elbasvir/grazoprevir for 12 weeks. Results for patients with GT6 infection were limited by the small number of GT6 patients enrolled. In a supportive efficacy analysis based on the full analysis set (FAS), which included all subjects with HCV GT1, 4 or 6 infection who received at least one dose of study drug, the overall SVR12 rate in the ITG was 92 percent (184/201).
Of the 301 patients evaluated across both treatment groups, 76 percent had GT1a infection, 21 percent had cirrhosis and 7 percent had HIV/HCV co-infection. All patients were on OAT at baseline. The use of non-prescribed drugs, such as cocaine and/or amphetamines, was observed in 59 percent of patients at baseline and remained steady throughout the trial; however, adherence to treatment with elbasvir/grazoprevir was high.
In the mFAS, virologic failures occurred in nine patients in the ITG, including seven relapses and two discontinuations for reasons deemed related to study drug; in the FAS, an additional five reinfections and three discontinuations for non-treatment related reasons were counted as treatment failures. Across the ITG on active study medication and DTG on placebo, four patients (1%) discontinued treatment due to adverse events (AE), including two patients (1%) in the ITG and two (2%) in the DTG. Two patients (1% across both groups) reported a serious drug-related AE (0.5% in the ITG, 1% in the DTG). The most common AEs in the ITG versus the DTG, respectively, were fatigue (16% versus 20%), headache (13% versus 14%), nausea (11% versus 9%) and diarrhea (10% versus 9%). One patient receiving placebo died for reasons unrelated to the study drug.
"Limited research has been conducted in people with chronic hepatitis C virus infection undergoing treatment for injection drug use because of the perceived challenges and complexities involved in treating this population," said Dr. Eliav Barr, vice president, infectious diseases, Merck Research Laboratories. "This is one of the largest clinical trials to date evaluating an all-oral, once-daily, ribavirin-free investigational treatment regimen for patients with chronic hepatitis C virus infection on opioid agonist therapy and reflects Merck's ongoing commitment to study the diverse real-world population of people living with this disease."
About Chronic HCV Infection and Opioid Agonist Therapy
Injection drug use is the most common risk factor for chronic HCV in the United States, and rates of transmission and reinfection are higher among injection drug users than in other people with HCV.i,ii In the United States, 67 percent to 84 percent of this population on OAT has been infected with HCV.iii
Elbasvir/grazoprevir is Merck's investigational, once-daily, fixed-dose combination therapy containing elbasvir (HCV NS5A replication complex inhibitor) and grazoprevir (HCV NS3/4A protease inhibitor). Merck's broad clinical trials program includes evaluations of elbasvir/grazoprevir with or without ribavirin for multiple HCV genotypes, together with patients with difficult-to-treat conditions, such as cirrhosis, advanced chronic kidney disease, HIV/HCV co-infection, inherited blood disorders and those on opioid agonist therapy. In July 2015, the U.S. Food and Drug Administration (FDA) granted Priority Review for the New Drug Application for elbasvir/grazoprevir with a Prescription Drug User Fee Act (PDUFA) action date of Jan. 28, 2016.
In April 2015, the FDA granted Breakthrough Therapy Designation for elbasvir/grazoprevir for the treatment of patients with chronic HCV GT1 infection with end stage renal disease on hemodialysis, and Breakthrough Therapy Designation for elbasvir/grazoprevir for the treatment of patients with chronic HCV GT4 infection. Breakthrough Therapy Designation is intended to expedite the development and review of a candidate that is planned for use, alone or in combination, to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.
Merck's Commitment to HCV
For nearly 30 years, Merck has been at the forefront of the response to the HCV epidemic. Merck employees are dedicated to applying their scientific expertise, resources and global reach to deliver innovative healthcare solutions that support people living with HCV worldwide.
Today's Merck is 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, NJ, USA
This news release of Merck & Co., Inc., Kenilworth, NJ, USA (the "company") 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 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 healthcare legislation in the United States and internationally; global trends toward healthcare 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 2014 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).
1 Elbasvir is an HCV NS5A replication complex inhibitor and grazoprevir is an HCV NS3/4A protease inhibitor.
i CDC (2015). Hepatitis C FAQs for Health Professionals. <http://www.cdc.gov/hepatitis/hcv/hcvfaq.htm>.
ii Grady BP et al. Hepatitis C virus reinfection following treatment among people who use drugs. Clin Infect Dis. 2013 Aug;57 Suppl 2:S105-10.
iii CDC (2002). Methadone Maintenance Treatment.
Doris Li, 908-246-5701
Sarra Herzog, 201-669-6570
Teri Loxam, 908-740-1986
Justin Holko, 908-740-1879