Real-World Study Shows ZEPATIER® (Elbasvir and Grazoprevir) Resulted in High Rates of Sustained Virologic Response in Patients with Chronic Hepatitis C Infection Who Have Chronic Kidney Disease


October 21, 2017 1:00 pm ET

Observational Analysis Evaluated Patients in U.S. Veterans Affairs System

Merck (NYSE:MRK), known as MSD outside of the United States and Canada,
today announced the presentation of findings from a retrospective
database analysis of patients with chronic hepatitis C virus (HCV)
genotype (GT) 1 or 4 infection who have chronic kidney disease (CKD) and
were treated with ZEPATIER® (elbasvir and grazoprevir) in the
U.S. Department of Veterans Affairs (VA) healthcare system. Among
patients who completed therapy, the analysis showed 95.6 percent
(714/747) of patients with severe CKD (stages 4-5, defined as estimated
glomerular filtration rate (eGFR) <30 mL/min/1.73 m2) and
97.1 percent (758/781) of patients with moderate CKD (stage 3, defined
as eGFR 30-59 mL/min/1.73 m2) achieved sustained virologic
response (SVR), defined as HCV RNA below the limit of quantification at
least 10-12 weeks after the end of treatment. For patients with missing
HCV RNA data after at least 10-12 weeks after treatment completion,
analyses were conducted on a post-hoc basis using the last HCV RNA data
available after week 4 after therapy completion. The response rates in
the real-world setting of the VA further supplement findings from controlled
clinical studies
 of ZEPATIER. These findings will be presented today
at The
Liver Meeting® 2017
taking place in Washington, D.C.

In the United States, ZEPATIER is indicated for the treatment of chronic
HCV GT1 or GT4 infection in adults. ZEPATIER is indicated for use with
ribavirin (RBV) in certain patient populations. The U.S. Prescribing
Information for ZEPATIER includes a Boxed Warning about the risk of
hepatitis B virus (HBV) reactivation in patients co-infected with HCV
and HBV. In controlled clinical studies of ZEPATIER, SVR was the primary
endpoint defined as HCV RNA less than lower limit of quantification at
12 weeks after the cessation of treatment (SVR12).

“These results demonstrate that U.S. veterans with chronic hepatitis C
infection can achieve virologic cure in a real-world setting despite
having co-morbid chronic kidney disease,” said Jennifer Kramer,
investigator, Center for Innovations in Quality, Effectiveness and
Safety at the Michael E. DeBakey VA Medical Center, Houston, Texas, and
assistant professor of medicine, department of medicine, Baylor College
of Medicine. “There is an ongoing need for an increased focus on
screening and treating veterans and others who are disproportionately
impacted by this disease.”

The retrospective observational analysis included 5,845 patients with
chronic HCV infection who received ZEPATIER (elbasvir and grazoprevir)
between February 1 and December 31, 2016. Patients were identified from
the VA Corporate Data Warehouse, a national repository of VA electronic
medical records. Presence of chronic kidney disease was measured via
eGFR, per the National Kidney Foundation’s Modification of Diet in Renal
Disease equation. Of 4,693 patients evaluated in the per protocol
population, 16.6 percent (781/4693) had CKD stage 3 and 15.9 percent
(747/4693) had CKD stages 4 or 5. Please see additional information
below about the design, methodology and limitations of this
observational analysis.

“Researching the needs of veterans is part of our collective
responsibility to those who have served our country,” said Susan Shiff,
senior vice president, Center for Observational and Real-World Evidence,
Merck. “The robust nature of VA medical data enables us to study the
effectiveness of ZEPATIER for the treatment of chronic hepatitis C
infection in people with kidney disease and other comorbid conditions in
that real-world setting.”

Adverse event data were not collected as part of this real-world data

Most patients with chronic kidney disease in the analysis were male
(96.9%, 1481/1528); African American (67.5%, 1031/1528) and either had
GT1a infection (52.2%, 798/1528) or GT1b infection (42.1%, 644/1528).
The mean age for patients in the study with chronic kidney disease was
64.9 years. Comorbid conditions as defined by ICD-9/10 codes in the VA
database included depression (58.5%, 894/1528), diabetes (69.2%,
1057/1528), compensated cirrhosis (18.6%, 284/1528), and HIV (5.0%,
76/1528). In the study, 19.9 percent of patients (304/1528) were coded
as having decompensated cirrhosis; ZEPATIER is not for use in patients
with moderate or severe hepatic impairment (Child Pugh B or C). See
Selected Safety Information below for more information.

Study Methodology

The database included patients ages 18 and older with chronic HCV
infection who initiated treatment with ZEPATIER between February 1,
2016, and December 31, 2016, and had at least one inpatient or
outpatient visit within a year prior to treatment (n=5845). The study
excluded patients without ≥2 eGFR values at least 90 days apart or
on-treatment HCV RNA data, patients who did not receive 12-16 weeks of
treatment with ZEPATIER and patients who received RBV >1 month after
initiating treatment (n=1152).

SVR was defined in the protocol for these analyses as HCV RNA below the
limit of quantification at least 10-12 weeks after the end of treatment.
For patients with missing HCV RNA data at week 10-12 after treatment
completion, analyses were conducted on a post-hoc basis using HCV RNA
data captured starting from week 4 after therapy completion. SVR data at
least 12 weeks after completion of therapy was available for 81.9% of
the analysis population.

About Real-World Data Analyses and Associated Limitations

Real-world studies analyze data generated outside of randomized clinical
trials, such as through analyses of electronic medical records or claims
databases, to provide insight into how medicines perform or are used
from a clinical and economic viewpoint in real-world clinical settings.
Information from real-world analyses alone does not provide sufficient
evidence to validate efficacy or safety of a therapeutic regimen and
does not provide a substitute for evidence obtained from randomized
controlled clinical trials.

This study is subject to certain limitations. The VA population may not
be generalizable to the entire U.S. population, due in part to the
potential for a differing demographic make-up and/or risk factors. Bias
may exist as diagnoses and co-morbidities were identified through
ICD-9/10 codes. Treatment completion was identified through prescription
records which may not reflect adherence. Database analyses are also
prone to errors in coding and missing data, including unavailable SVR
data. Additionally, some laboratory data including data on the presence
of baseline NS5A resistance associated substitutions was not available
at the time of this analysis.

About the VA Corporate Data Warehouse (CDW)

The Department of Veterans Affairs Veterans Healthcare Administration
(VHA) is supported by one of the largest integrated healthcare
information systems in the United States. The VHA’s Corporate Data
Warehouse (CDW) was developed in 2006 to accommodate the massive amounts
of data being generated from more than 20 years of use and to streamline
the process of knowledge discovery to application.



(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. In
the United States, ZEPATIER is indicated for the treatment of chronic
HCV GT1 or 4 infection in adults. ZEPATIER is indicated for use with
ribavirin (RBV) in certain patient populations. The efficacy of ZEPATIER
has not been established in patients who have previously failed
treatment with other regimens that included an NS5A inhibitor.

Selected Safety Information about ZEPATIER

The US Prescribing Information for ZEPATIER contains a Boxed Warning
about the risk of hepatitis B virus (HBV) reactivation in patients
coinfected with HCV and HBV. Healthcare professionals should test all
patients for evidence of current or prior HBV infection by measuring
hepatitis B surface antigen (HBsAg) and hepatitis B core antibody
(anti-HBc) before initiating treatment with ZEPATIER. HBV reactivation
has been reported in HCV/HBV coinfected patients who were undergoing or
had completed treatment with HCV direct-acting antivirals and were not
receiving HBV antiviral therapy. Some cases have resulted in fulminant
hepatitis, hepatic failure, and death. Healthcare professionals should
monitor HCV/HBV coinfected patients for clinical and laboratory signs of
hepatitis flare or HBV reactivation during HCV treatment and
post-treatment follow-up. Healthcare professionals should initiate
appropriate patient management for HBV infection as clinically indicated.

HBV reactivation has been reported in HBsAg positive patients and also
in patients with serologic evidence of resolved HBV infection (ie, HBsAg
negative and anti-HBc positive). The risk of HBV reactivation may be
increased in patients receiving some immunosuppressant or
chemotherapeutic agents. HBV reactivation is characterized as an abrupt
increase in HBV replication manifesting as a rapid increase in serum HBV
DNA level. In patients with resolved HBV infection, reappearance of
HBsAg can occur. Reactivation of HBV replication may be accompanied by
hepatitis, ie, increases in aminotransferase levels and, in severe
cases, increases in bilirubin levels, liver failure, and death can occur.

ZEPATIER (elbasvir and grazoprevir) is not for use in patients with
moderate or severe hepatic impairment (Child Pugh B or C). ZEPATIER is
also not for use with inhibitors of organic anion transporting
polypeptides 1B1/3 (OATP1B1/3) that are known or expected to
significantly increase grazoprevir plasma concentrations (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
(elbasvir and grazoprevir) 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 (elbasvir and grazoprevir) 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 Merck

For more than a century, Merck, a leading global biopharmaceutical
company known as MSD outside of the United States and Canada, has been
inventing for life, bringing forward medicines and vaccines for many of
the world’s most challenging diseases. 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. Today, Merck continues to be at the forefront of
research to advance the prevention and treatment of diseases that
threaten people and communities around the world – including cancer,
cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease
and infectious diseases including HIV and Ebola. For more information,
and connect with us on TwitterFacebookInstagram,
and LinkedIn.

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. 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 2016 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), including the Boxed Warning about the risk of hepatitis B
virus (HBV) reactivation in patients coinfected with HCV and HBV, at

and the Patient Information for ZEPATIER at

Pam Eisele, 267-305-3558
Michael Close, 267-305-1211
Teri Loxam, 908-740-1986
Amy Klug, 908-740-1898

Unsubscribe from email alerts