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 4:05 pm ET

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 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
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

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.

About Merck

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
and connect with us on Twitter,
and LinkedIn.

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# # #

Please see Prescribing Information for ZEPATIER (elbasvir and
grazoprevir) at

and the Patient Information for ZEPATIER at

Pamela Eisele, 267-305-3558
Sarra Herzog, 201-669-6570
Teri Loxam, 908-740-1986
Amy Klug, 908-740-1898

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