Results from Merck’s Phase 3 Study Evaluating ZEPATIER™ (elbasvir and grazoprevir) in Patients with Chronic Hepatitis C Receiving Treatment for Opioid Dependence Published in Annals of Internal Medicine
August 8, 2016 KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the publication of results from C-EDGE CO-STAR . C-EDGE CO-STAR is a Phase 3 trial evaluating the use of ZEPATIER™ (elbasvir and grazoprevir) 50mg/100mg tablets in patients with chronic hepatitis C (HCV) genotype (GT) 1, GT4 and GT6 infection receiving opioid agonist therapy (OAT) (methadone and buprenorphine), commonly used to treat opioid addiction. The results, recently published online in the Annals of Internal Medicine , showed treatment with 12 weeks of ZEPATIER resulted in high rates of sustained virologic response 12 weeks after the completion of therapy (SVR12, considered virologic cure based on undetectable HCV RNA levels). These results and full study design were previously presented at The Liver Meeting® in November 2015.
“C-EDGE CO-STAR is the first phase 3 clinical trial dedicated to evaluating direct-acting antiviral therapy for chronic hepatitis C infection in patients on opioid agonist therapy without excluding patients actively using drugs with high abuse potential,” said Dr. Alain Litwin, professor of medicine and psychiatry and behavioral sciences at Albert Einstein College of Medicine, New York. “This study demonstrates that people who inject drugs can be effectively treated with direct-acting antiviral therapy.”
The published efficacy results from the randomized, double-blind, placebo-controlled C-EDGE CO-STAR trial showed 92 percent (184/201) of patients receiving ZEPATIER for 12 weeks in the study’s immediate treatment group achieved SVR12, with comparable rates across GT1a (94%, 144/154), GT1b (93%, 28/30) and GT4 (92%, 11/12) patients; in the limited number of GT6 patients, SVR12 was 20 percent (1/5). These results classify patients who cleared their baseline infection but subsequently acquired a new infection as treatment failures; previously presented results from this trial considered these patients as treatment successes, according to the study protocol. A supportive analysis showed that the vast majority of patients were adherent to therapy, despite ongoing use of drugs of potential abuse (e.g., cocaine, heroin, amphetamines) by the majority of patients throughout the trial. The rates of adverse events were generally comparable between active treatment and placebo groups, with the most common adverse events (greater than 10%) in both groups including fatigue (16%, 20%), headache (12%, 13%) and nausea (11%, 9%), respectively. Secondary efficacy endpoint (SVR24) and reinfection analyses were presented at The International Liver Congress™ in April 2016.
“Merck continues to take a leadership role in exploring the potential to treat chronic hepatitis C infection in underserved and undertreated patient populations, including those who continue to use illicit drugs,” said Dr. Eliav Barr, vice president, infectious diseases, Merck Research Laboratories. “These findings contribute to the robust body of evidence supporting the efficacy and safety profile of ZEPATIER in a broad range of patients with chronic hepatitis C genotype 1 or genotype 4 infection.”
About ZEPATIER™ (elbasvir and grazoprevir) 50mg/100mg Tablets
ZEPATIER is a fixed-dose combination product containing elbasvir, a HCV NS5A inhibitor, and grazoprevir, an HCV NS3/4A protease inhibitor, and is indicated with or without ribavirin (RBV) for treatment of chronic HCV GT 1 or 4 infection in adults. ZEPATIER is not indicated to treat chronic HCV GT6 infection.
Selected Safety Information about ZEPATIER
ZEPATIER is not for use in patients with moderate or severe hepatic impairment (Child Pugh B or C). ZEPATIER is also not for use with organic anion transporting polypeptides 1B1/3 (OATP1B1/3) inhibitors (e.g., atazanavir, darunavir, lopinavir, saquinavir, tipranavir, cyclosporine), strong cytochrome P450 3A (CYP3A) inducers (e.g., carbamazepine, phenytoin, rifampin, St. John’s Wort), and efavirenz. If ZEPATIER is administered with RBV, healthcare professionals should refer to the prescribing information for RBV as the contraindications, warnings and precautions, adverse reactions and dosing for RBV also apply to this combination regimen.
Elevations of alanine transaminase (ALT) to greater than 5 times the upper limit of normal (ULN) occurred in 1% of subjects, generally at or after treatment week 8. These late ALT elevations were typically asymptomatic and most resolved with ongoing or completion of therapy. Healthcare professionals should perform hepatic lab testing on patients prior to therapy, at treatment week 8, and as clinically indicated. For patients receiving 16 weeks of therapy, additional hepatic lab testing should be performed at treatment week 12.
Patients should be instructed to consult their healthcare professional without delay if they have onset of fatigue, weakness, lack of appetite, nausea and vomiting, jaundice or discolored feces. Healthcare providers should consider discontinuing ZEPATIER if ALT levels remain persistently greater than 10 times ULN. ZEPATIER should be discontinued if ALT elevation is accompanied by signs or symptoms of liver inflammation or increasing conjugated bilirubin, alkaline phosphatase, or international normalized ratio.
The concomitant use of ZEPATIER with certain drugs may lead to adverse reactions or reduced therapeutic effect due to drug interactions. Certain strong CYP3A inhibitors may increase the plasma concentration of ZEPATIER, leading to possibly clinically significant adverse reactions. Moderate CYP3A inducers may decrease the plasma concentration of ZEPATIER, leading to reduced therapeutic effect and possible development of resistance. Coadministration of ZEPATIER with these drugs is not recommended. Physicians should consult the Prescribing Information for potential drug interactions.
In subjects receiving ZEPATIER for 12 weeks, the most commonly reported adverse reactions of all intensity (greater than or equal to 5% in placebo-controlled trials) were fatigue, headache and nausea. In subjects receiving ZEPATIER with RBV for 16 weeks, the most commonly reported adverse reactions of moderate or severe intensity (greater than or equal to 5%) were anemia and headache.
Selected Dosage and Administration Information for ZEPATIER (elbasvir and grazoprevir)
ZEPATIER is a single tablet taken once daily. The recommended dosing is 12 or 16 weeks with or without RBV, depending on HCV genotype, prior treatment history and, for patients with genotype 1a infection, presence of certain baseline NS5A resistance-associated polymorphisms. See Prescribing Information for ZEPATIER for specific dosage regimens and durations. Refer to RBV prescribing information for RBV dosing and dosage modifications when ZEPATIER is given with RBV. To determine dosage regimen and duration of ZEPATIER for genotype 1a patients, testing for the presence of virus with one or more baseline NS5A resistance-associated polymorphisms at positions 28, 30, 31, or 93 is recommended prior to initiating treatment.
About Chronic HCV Infection and Injection Drug Use
Injection drug use is responsible for the majority of new and existing HCV infections in high-income countries. It is estimated that 60 to 80 percent of people who inject drugs are tested positive with chronic HCV infection.
Merck’s Commitment to HCV
For more than 30 years, Merck has been at the forefront of the response to the HCV epidemic. Merck’s chronic HCV clinical development programs have included more than 135 clinical trials in approximately 40 countries and have enrolled nearly 10,000 participants. As part of our longstanding leadership in infectious diseases, Merck collaborates with the scientific and patient communities to develop and deliver innovative solutions to support people living with chronic HCV worldwide.
For 125 years, 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.
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).
# # #
Please see Prescribing Information for ZEPATIER (elbasvir and grazoprevir) at http://www.merck.com/product/usa/pi_circulars/z/zepatier/zepatier_pi.pdf and the Patient Information for ZEPATIER at http://www.merck.com/product/usa/pi_circulars/z/zepatier/zepatier_ppi.pdf