Findings Presented at The International
Liver Congress™ 2017 Show High Rates of Sustained Virologic
Response (SVR12) in Genotype 1 Patients for Whom Direct-Acting
Antiviral Therapy Had Previously Failed
Merck (NYSE: MRK), known as MSD outside of the United States and
Canada, today announced the first sustained virologic response1
(SVR) results 12 weeks after completion of therapy (SVR12,
considered virologic cure) from C-SURGE, an ongoing, open label
Phase 2 clinical trial evaluating MK-3682B [uprifosbuvir
(MK-3682)2/grazoprevir3/rusazvir4], the company’s investigational
triple-combination therapy in treatment-experienced patients with
hepatitis C virus (HCV) genotype (GT) 1 infection for whom
treatment with approved direct-acting antiviral regimens had
failed. The study showed that 100 percent (43/43) of patients who
completed 16 weeks of treatment plus ribavirin (RBV) achieved SVR12
and 100 percent (49/49) of patients who completed 24 weeks of
treatment achieved SVR12 (abstract PS-159). These results will be
presented today at The International Liver Congress™ 2017.
“Despite the significant progress made to address the worldwide
epidemic of chronic hepatitis C infection, there remains a need for
additional treatment options,” said Dr. Heiner Wedemeyer, lead
study investigator and research group leader in the department of
gastroenterology, hepatology and endocrinology at Hannover Medical
School, Germany. “We are encouraged by the high virologic cure
rates in the difficult-to-treat patients observed in the C-SURGE
study and look forward to further evaluation of this
investigational triple-combination therapy.”
The Phase 2 C-SURGE study enrolled 94 patients who were
randomized to receive a once-daily regimen of MK-3682B for either
16 weeks with RBV (n=45) or 24 weeks without RBV (n=49); one
patient in the 16-week arm withdrew prior to starting treatment. Of
the 93 patients who received treatment (full analysis set), 57 had
previously received a regimen of ledipasvir/sofosbuvir (LDV/SOF)
for 12 to 24 weeks, 14 had previously received LDV/SOF for 8 weeks
and 22 had previously received ZEPATIER® (elbasvir and grazoprevir)
for 12 weeks. Seventy-eight patients who received treatment had at
least one baseline NS5A resistance-associated substitution (RAS) at
positions 28, 30, 31 or 93. Eighty patients who received treatment
in C-SURGE had GT1a infection, and 40 patients had compensated
cirrhosis. In the full analysis set, 98 percent of patients who
received MK-3682B for 16 weeks with RBV (43/44) and 100 percent of
patients who received MK-3682B for 24 weeks without RBV (49/49)
achieved SVR12.
Results from the modified full analysis set, which excludes one
patient in the 16-week arm who withdrew after three doses of
treatment, show that 100 percent of patients receiving treatment
with MK-3682B for 16 weeks with RBV (43/43) and 100 percent of
patients receiving treatment with MK-3682B for 24 weeks without RBV
(49/49) achieved SVR12.
Across the combined treatment arms, the most common adverse
events (AEs) reported in the full analysis set were fatigue (35%),
headache (13%), diarrhea (9%), rash (9%) and pruritus (5%). There
were no drug-related serious AEs, and no patients discontinued
treatment due to a drug-related AE.
SVR8 results from the C-SURGE study were previously presented at
The Liver Meeting® 2016.
About MK-3682B
MK-3682B is Merck’s investigational triple-combination therapy
in Phase 2 development for the treatment of chronic HCV infection.
MK-3682B combines an HCV nucleotide analogue NS5B polymerase
inhibitor (MK-3682), an HCV NS3/4A protease inhibitor (grazoprevir,
MK-5172) and an HCV NS5A inhibitor (ruzasvir, MK-8408).
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.
Selected Safety Information about ZEPATIER (elbasvir and
grazoprevir)
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 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
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
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 more than a century, Merck, a leading global
biopharmaceutical company known as MSD outside of the United States
and Canada, has been 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.
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 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) 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
______________________1 Measured as HCV RNA less than 15 IU/mL.2
MK-3682 is an HCV nucleotide analogue NS5B polymerase inhibitor.3
Grazoprevir is an HCV NS3/4A protease inhibitor (100mg).4 Rusazvir
(MK-8408) is an HCV NS5A inhibitor.
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version on businesswire.com: http://www.businesswire.com/news/home/20170422005018/en/
MerckMedia:Doris Li, 908-740-1903Michael Close,
267-305-1211orInvestors:Teri Loxam, 908-740-1986Amy Klug,
908-740-1898
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