Merck Announces Findings for Investigational Triple-Combination Chronic Hepatitis C Therapy Showing High Rates of Sustained Virologic Response in People with Genotypes 1, 2 or 3 Infection


November 13, 2016 8:00 am ET

Phase 2 Data Presentations at The Liver Meeting ® Detail SVR12 Rates from Two Studies as Well as SVR8 Rates in Patients for Whom Direct-Acting Antiviral Treatment Previously Failed

KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside of the United States and Canada,
today announced the presentation of results from three Phase 2 clinical
trials evaluating MK-3682B (MK-3682/grazoprevir/ruzasvir1),
the company’s investigational all-oral, triple-combination regimen for
the treatment of chronic hepatitis C (HCV) infection (informally
referred to as MK3). Results from Part B of


demonstrated high rates of sustained virologic response2
(SVR) 12 weeks after the completion of therapy (SVR12, considered
virologic cure) in patients with chronic HCV genotype (GT) 1 or GT3
infection who received eight weeks of treatment with MK-3682B. Findings
from C-CREST 1 & 2 Part B also demonstrated high rates
of SVR12 in GT1, GT2 and GT3-infected patients who received MK3 for 12
or 16 weeks. Findings from Part C of


and interim results from the ongoing

study showed high rates of SVR12 and SVR8, respectively, in chronic HCV
patients who had failed prior treatment with investigational or approved
direct-acting antiviral regimens. These results will be announced in
oral presentations at The
Liver Meeting® 2016
today (C-CREST 1 & 2 Parts
B and C) and tomorrow (C-SURGE).

“Across the chronic hepatitis C treatment landscape, incredible progress
has been made in a remarkably short amount of time, but there remains a
need for more options, particularly for patients who do not achieve
sustained virologic response with treatment regimens available today,”
said Dr. Eliav Barr, senior vice president, global clinical development,
infectious diseases and vaccines, Merck Research Laboratories. “The
strong findings observed following treatment with MK-3682B are an
encouraging step towards Merck’s goal of developing and delivering a
shorter-duration, pan-genotypic next-generation treatment regimen for
more patients with chronic hepatitis C infection.”


& 2 Part B Overview and Findings

Part B of C-CREST 1 & 2 – ongoing, open-label Phase 2
clinical trials – was designed to evaluate the safety and efficacy of
MK-3682B in patients with chronic HCV GT1, GT2 or GT3 infection, with or
without cirrhosis. Patients with GT2 or GT3 infection received MK-3682B
with or without RBV. All patients with GT1 or GT2 infection were
treatment-naïve. Fifty six percent (189/337) of patients with GT3
infection were treatment naïve and 44 percent (148/337) were previously
treated with peginterferon/ribavirin (RBV). The primary endpoint of the
study was the proportion of patients in each treatment arm who achieved

Eight weeks of treatment with MK-3682B resulted in SVR12 rates of 95
percent, 86 percent and 95 percent in GT1, GT2 and GT3 patients,
respectively. A 12-week treatment duration resulted in high SVR12 rates
in all genotypes (GT1, 99%; GT2, 97%; GT3, 97%). Efficacy was comparable
in patients with and without cirrhosis. There were no virologic failures
in the patients with GT1 or GT2 infection who received 12 weeks of
MK-3682B. Efficacy results are presented in the table below. Results
from Part A of C-CREST 1 & 2 were previously reported
at The
Liver Meeting® in November 2015


Summary of SVR12 Findings

Population     N     MK-3682B

+/- RBV

8 weeks


+/- RBV

12 weeks


+/- RBV

16 weeks

GT1a     90     93% (39/42)     98% (47/48)    
GT1b     86     98% (45/46)     100% (40/40)    
GT2     151     86% (54/63)     97% (60/62)     100% (26/26)
GT3*     337     95% (98/103)     97% (155/159)     96% (72/75)

*28 percent (29/103), 36 percent (58/159) and 81 percent (61/75)
patients with GT3 infection receiving eight, 12 or 16 weeks
therapy, respectively, were previously treated with


Among patients who received at least one dose of MK-3682B with or
without RBV, the overall most common adverse events (AEs) reported
(greater than 10% incidence in either treatment arm) were headache
(22%), fatigue (19%) and nausea (13%). There were two drug-related
serious AEs, both considered related to RBV only. Nine patients
discontinued study drug due to AEs, four of whom discontinued RBV only.
One patient died due to AEs not related to the study drug.

“As a scientist and physician who regularly treats patients with chronic
hepatitis C, the importance of continuing to research this complex
disease and its many complications is evident,” said Dr. Eric Lawitz,
vice president, scientific and research development, The Texas Liver
Institute and clinical professor of medicine, The University of Texas
Health Science Center, San Antonio. “The virologic cure rates observed
in Part B of C-CREST 1 & 2 clearly demonstrate the
potential for MK3 and support further study of this investigational


Overview and Preliminary Findings

C-SURGE is an ongoing, open-label Phase 2 clinical trial designed
to evaluate MK-3682B with or without RBV in chronic HCV GT1 patients who
previously failed therapy with either ledipasvir/sofosbuvir (LDV/SOF) or
ZEPATIER™ (elbasvir and grazoprevir). The study enrolled 94 patients
randomized to receive 16 weeks of MK-3682B plus RBV (n=45) or 24 weeks
of MK-3682B without ribavirin (n=49); one patient in the 16 week arm
withdrew prior to starting treatment. Of the 93 patients who received
treatment in this study, 61 percent (57/93) had previously received 12
to 24 weeks of treatment with LDV/SOF; 15 percent (14/93) had received 8
weeks of LDV/SOF; and 24 percent (22/93) had received 12 weeks of
ZEPATIER. A majority of patients (84%, 78/93) had at least one baseline
NS5A resistance-associated variant (RAV) at positions 28, 30, 31 or 93.

Interim results from the modified full analysis set (mFAS), which
excludes one patient in the 16-week arm who withdrew due to
administrative reasons after receiving three doses of study medication,
show all patients (43/43) who have completed treatment with MK-3862B
plus RBV for 16 weeks achieved SVR8. All patients (49/49) in the mFAS
who received MK-3682B for 24 weeks have completed treatment and remain
subject to follow-up; the interim results show of those in the 24-week
arm who have reached follow-up weeks four and eight, 100 percent have
achieved SVR4 (38/38) and SVR8 (30/30), respectively. SVR12 is the
primary outcome measure of this ongoing trial. Final results will be
presented at a future scientific congress.

Among patients who received at least one dose of MK-3682B with or
without RBV, the overall most common AEs reported were fatigue (35%),
headache (13%), diarrhea (9%), rash (9%) and pruritus (5%). There were
no drug-related serious AEs, and no patients discontinued due to a
drug-related AE.

C-CREST 1 & 2

Part C Overview and Findings

Part C of C-CREST 1 & 2 was designed to evaluate
retreatment with MK-3682B plus RBV for 16 weeks among patients who
previously failed an investigational triple-therapy regimen
(MK-3682/grazoprevir/ruzasvir or MK-3682/grazoprevir/elbasvir). The
study enrolled 24 patients with GT1 (n=2), GT2 (n=14) or GT3 (n=8)
infection. All patients (23/23) who completed treatment achieved SVR12.
One GT2 patient discontinued treatment after a single dose due to
drug-related serious AEs. Among patients who received at least one dose
of MK-3682B plus RBV, the most common AEs reported (greater than 20%
incidence) were headache (33%), fatigue (25%), nausea (25%), rash (21%)
and insomnia (21%).

About MK-3682B

MK-3682B (informally referred to as MK3) 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) 50 mg/100mg tablets

ZEPATIER is a fixed-dose combination product containing elbasvir, an HCV
NS5A inhibitor, and grazoprevir, an HCV NS3/4A protease inhibitor.
ZEPATIER is indicated with or without ribavirin (RBV) for treatment of
chronic HCV genotypes 1 or 4 infection in adults.

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
and connect with us on Twitter,
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
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Reform Act of 1995. These statements are based upon the current beliefs
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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
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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 MK-3682 is an HCV nucleotide analogue NS5B polymerase
inhibitor. Grazoprevir (MK-5172) is an HCV NS3/4A protease inhibitor.
Ruzasvir (MK-8408) is an HCV NS5A inhibitor.

2 Measured as HCV RNA less than 15 IU/mL.

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

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