What can we help you find?

April 22, 2017 6:00 am ET

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.

Merck
Media:
Doris Li, 908-740-1903
Michael Close, 267-305-1211
or
Investors:
Teri Loxam, 908-740-1986
Amy Klug, 908-740-1898