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 analysis.
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.
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. 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,
visit www.merck.com and connect with us
on Twitter, Facebook, Instagram, YouTube
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 (www.sec.gov).
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
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
View source
version on businesswire.com: http://www.businesswire.com/news/home/20171021005005/en/
MerckMedia:Pam Eisele, 267-305-3558orMichael Close,
267-305-1211orInvestors:Teri Loxam, 908-740-1986orAmy Klug,
908-740-1898
Merck (NYSE:MRK)
Historical Stock Chart
From Apr 2024 to May 2024
Merck (NYSE:MRK)
Historical Stock Chart
From May 2023 to May 2024