Merck Announces Presentation of New Findings for ZEPATIER™ (Elbasvir and Grazoprevir) in Patients with Chronic Hepatitis C at The Liver Meeting®


November 12, 2016 8:00 am ET

KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside of the United States and Canada,
today announced results from multiple analyses at The
Liver Meeting® 2016
, which provide additional evidence
supporting the use of ZEPATIER™ (elbasvir and grazoprevir) 50mg/100mg
tablets in chronic hepatitis C virus (HCV) genotype (GT) 1- or
GT4-infected patient populations, including those who receive opioid
agonist therapy (OAT), are infected with chronic HCV GT1b, use proton
pump inhibitors (PPIs) or have moderate kidney disease.

“Work remains to be done in the community’s efforts to reduce the global
burden of chronic hepatitis C, and Merck is committed to pursuing this
goal,” said Dr. Eliav Barr, senior vice president, global clinical
development, infectious diseases and vaccines, Merck Research
Laboratories. “Our clinical development program continues to yield
meaningful evidence for ZEPATIER in specific patient populations.”


: Interim Results from the Three Year
Follow-Up (3YFU) Trial (Abstract #871)

The CO-STAR Three Year Follow-Up (3YFU) Trial is an observational
cohort study to evaluate chronic HCV reinfection and injecting risk
behaviors in patients who were treated with ZEPATIER during the

study. C-EDGE CO-STAR is a Phase 3 clinical trial
including patients with chronic HCV GT1, GT4 and/or GT6 infection who
are on OAT (methadone and buprenorphine). The study does not exclude
patients who are actively using drugs with high abuse potential. Primary
efficacy and safety results from C-EDGE CO-STAR were previously
presented at The
Liver Meeting® in November 2015
. Interim results
presented today are from the ongoing 3YFU study.

The median time from the end-of-treatment (EOT) in the C-EDGE CO-STAR
study to the first visit as part of the 3YFU study was 330 days (range:
206-485). Of the 199 patients in the 3YFU study, 108 (54%) reported any
drug use (non-injecting or injecting) in the past six months, 40 of whom
(37%) reported injection drug use in the past month. At the first visit
in the 3YFU study, two individuals (1%) tested positive for evidence of
HCV, suggesting that chronic HCV reinfection was uncommon among patients
on OAT in the first year following treatment with ZEPATIER, despite
ongoing drug use.

GT1b Integrated Analysis (Abstract #874)

A retrospective integrated analysis of data from 11 Phase 2 and Phase 3
trials in the clinical development program for ZEPATIER was conducted to
evaluate its efficacy in patients infected with GT1b, the most common
chronic HCV genotype globally and the second-most common in the United
States. The analysis included 1,070 patients with chronic HCV GT1b
infection who received ZEPATIER for 12 weeks, including: patients who
were treatment naïve or had prior experience with peginterferon
alfa/interferon and ribavirin (RBV), with or without an NS3/4A protease
inhibitor; those who were compensated cirrhotic or non-cirrhotic; and
those with or without HIV-1 co-infection.

The analysis showed 97 percent of patients (1040/1070) achieved
sustained virologic response 12 weeks after the completion of therapy
(SVR12, considered virologic cure). Of the patients who did not achieve
SVR12, 15 were virologic failures (1%) and 15 patients were lost to
follow-up (1%). Rates of SVR12 were consistently high regardless of
patient characteristics, including prior treatment experience (97%,
212/219), presence of compensated cirrhosis (99%, 188/189) and HIV-1
co-infection (94%, 51/54).

Serious adverse events occurred in 3 percent of patients (35/1070) who
received active treatment, and 2.9 percent (3/105) of those who received
placebo in studies that included a placebo arm.

Pooled Analysis in Patients with Self-Reported PPI Use (Abstract #869)

This post-hoc analysis of patients with chronic HCV GT1 and GT4
infection in six studies in the Phase 3 clinical program for ZEPATIER
assessed SVR12 among patients who self-reported concomitant use of
proton pump inhibitors (PPIs). Pharmacokinetic interactions leading to
reduced drug concentrations have previously been reported for some HCV
NS5A inhibitors when given concomitantly with PPIs.

Overall, 12 percent (162/1322) of patients in the post-hoc analysis who
received ZEPATIER reported baseline use of PPIs. Of those patients, 96
percent (155/162) achieved SVR12, compared to 97 percent (1129/1160) of
patients without PPI use, suggesting that PPI use was not a predictive
factor in achieving SVR12.

This abstract received Presidential Poster of Distinction recognition at The
Liver Meeting® 2016

Pooled Dataset Analysis in Patients with Moderate Kidney Disease
(Abstract #889)

This integrated analysis of data from the Phase 2 and Phase 3 clinical
development program for ZEPATIER was conducted to evaluate its impact on
renal function, including in patients with chronic kidney disease (CKD)
stage 3 (estimated glomerular filtration rate [eGFR] less than 60 and
greater than or equal to 30 mL/min/1.73m2).1 The
safety and efficacy profile of ZEPATIER in patients with more severe
renal disease was described in the

study, presented at the
International Liver Congress™ in April 2015
and subsequently
published in The Lancet by Roth et al.

The analysis included 32 patients with stage 3 CKD and 1,657 patients
with eGFR greater than or equal to 60 mL/min/1.73m2 who were
treated with ZEPATIER with or without RBV for 8 (n=91, 5%), 12 (n=1238,
73%), 16 (n=211, 12%), or 18 (n=149, 9%) weeks. Among the 32 patients
with stage 3 CKD, kidney function improved or remained stable in 38
percent (12/32) and 63 percent (20/32), respectively, at the end of

About ZEPATIER™ (elbasvir and grazoprevir) 50mg/100mg Tablets

ZEPATIER is a fixed-dose combination product containing elbasvir, an HCV
NS5A inhibitor, and grazoprevir, an HCV NS3/4A protease inhibitor. In
the United States, ZEPATIER is indicated with or without ribavirin (RBV)
for treatment of chronic HCV GT1 or 4 infection in adults. ZEPATIER is
not indicated to treat chronic HCV GT6 infection. ZEPATIER was approved
in the United States on January 28, 2016, and is also approved in the
European Union, Canada, Japan, Australia, Saudi Arabia, Israel and
Switzerland, with additional regulatory approvals anticipated.

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.

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
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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
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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
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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 (

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

and the Patient Information for ZEPATIER at


1 Estimated glomerular filtration rate (eGFR) is a measure of
kidney function.

Doris Li, (908) 246-5701
Sarra Herzog, (201) 669-6570
Teri Loxam, (908) 740-1986
Amy Klug, (908) 740-1898

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