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April 23, 2015 2:30 am ET

C-SURFER Trial is First to Investigate an All-Oral Ribavirin-Free Hepatitis C Treatment Regimen in Treatment-Naïve and Treatment-Experienced Patients with Advanced Chronic Kidney Disease Infected with Hepatitis C Virus Genotype 1

KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced the first presentation of data from C-SURFER, the
company’s Phase 2/3 clinical trial evaluating the investigational
once-daily treatment regimen of grazoprevir (100mg) and elbasvir (50mg)
in patients with advanced chronic kidney disease (CKD) infected with
chronic hepatitis C virus (HCV) genotype 1 (GT1).¹
Treatment-naïve patients and patients who failed prior pegylated
interferon HCV therapy, with or without cirrhosis, all of whom had CKD
stages 4 or 5, were enrolled.² Following 12 weeks of
treatment with grazoprevir and elbasvir, 99 percent (115/116) of
patients in the pre-specified primary population for analysis of
efficacy data achieved a sustained virologic response 12 weeks after the
completion of treatment (SVR12).³ These data will be
presented today at The
International Liver Congress^TM 2015 – the 50^th
annual congress of the European Association for the Study of the Liver
(late breaking E-Poster #LP02).

“There is an unmet medical need to treat chronic hepatitis C virus
infection in patients with advanced chronic kidney disease,” said Dr.
Howard Monsour, Jr., chief of hepatology, Houston Methodist Hospital,
Houston, Texas. “In this trial, the first to investigate an all-oral
ribavirin-free treatment regimen in treatment-naïve and
treatment-experienced CKD patients, treatment with grazoprevir and
elbasvir for 12 weeks was effective in this study population with HCV
genotype 1 infection.”

The ongoing C-SURFER Phase 2/3 clinical trial is a randomized,
parallel-group, placebo-controlled study evaluating patients infected
with chronic HCV GT1 with advanced CKD with or without liver cirrhosis.
Patients were randomized to one of two study arms:

• Immediate treatment group (ITG), grazoprevir plus elbasvir (blinded)
  once-daily for 12 weeks (n=111);
• Deferred treatment group (DTG), initially placebo (control arm) for 12
  weeks followed by a four week follow-up period and then treatment with
  grazoprevir plus elbasvir (open label) once-daily for 12 weeks (n=113).

In addition, 11 patients received grazoprevir plus elbasvir (open label)
once-daily for 12 weeks with intensive pharmacokinetic sampling.

Of the 122 patients who received grazoprevir plus elbasvir, 83 percent
were treatment-naïve, 36 percent had diabetes, 18 percent had stage 4
CKD, 82 percent had stage 5 CKD, 75 percent were receiving hemodialysis
and 45 percent were African-American. Among those patients who received
at least one dose of grazoprevir plus elbasvir, five percent (6/122)
were excluded from the pre-specified primary efficacy analysis
population, or modified full analysis set, due to missing data caused by
death or early discontinuation for reasons unrelated to study drug. In
the modified full analysis set, 99 percent (115/116) of patients
receiving grazoprevir plus elbasvir achieved SVR12. One GT1b infected,
non-cirrhotic, interferon-intolerant patient showed a viral relapse at
follow-up week 12. Within the modified full analysis set, efficacy was
consistent across the patient sub-populations assessed. In a supportive
analysis of all 122 patients who received at least one dose of
grazoprevir plus elbasvir in the ITG arms, including patients who did
not complete the study for reasons not related to study drug, 94 percent
(115/122) of patients achieved SVR12.

“Merck’s broad clinical development program includes studies dedicated
to bringing a once-daily regimen to diverse populations of patients
infected with chronic HCV, including certain types of patients with
co-morbidities, such as advanced chronic kidney disease,” said Dr. Eliav
Barr, vice president, infectious diseases, Merck Research Laboratories.
“These data highlight how emerging innovations in chronic hepatitis C
treatment may lead to new options for patient populations in which it
historically has been difficult to achieve high rates of sustained viral
clearance.”

No patients in the ITG arms discontinued treatment due to adverse events
(AEs), while four percent (5/113) of patients in the comparator placebo
phase of the DTG arm discontinued treatment due to AEs. The rates of
serious AEs reported were 14 percent (16/111) in the ITG arms and 17
percent (19/113) in the placebo control DTG arm. The most common
treatment-related AEs in the ITG arms and DTG arm (placebo) were
headache (17%, 17%), nausea (15%, 16%) and fatigue (10%, 15%),
respectively. There were four deaths reported during the initial
treatment phase and the first 14 days of study follow-up. One patient
(1%) in the open label arm died from cardiac arrest (not considered
related to study medicine) and three patients (2%) in the placebo group
died from aortic aneurysm, pneumonia and an unknown cause.

On April 8, 2015, the company announced that the U.S. Food and Drug
Administration (FDA) had granted Breakthrough Therapy designation to
grazoprevir/elbasvir for the treatment of patients infected with chronic
HCV GT1 with end-stage renal disease on hemodialysis and patients
infected with chronic HCV GT4. Breakthrough Therapy designation is
intended to expedite the development and review of a candidate that is
planned for use, alone or in combination, to treat a serious or
life-threatening disease or condition when preliminary clinical evidence
indicates that the drug may demonstrate substantial improvement over
existing therapies on one or more clinically significant endpoints.

About C-SURFER

C-SURFER
is a Phase 2/3 clinical trial evaluating Merck’s investigational
grazoprevir plus elbasvir in patients infected with chronic HCV GT1 and
with advanced chronic kidney disease (stages 4 and 5, including patients
on hemodialysis) with or without liver cirrhosis, which are among those
with HCV infection who are most difficult to treat, over 12 weeks.

About Chronic HCV Infection and Chronic Kidney Disease

Chronic HCV infection is both a cause and complication of the treatment
of CKD. In patients with CKD, chronic HCV infection is associated with
an increased risk of accelerated loss of remaining kidney function,
kidney transplant failure and death. Furthermore, patients with chronic
HCV infection and advanced CKD represent an unmet need due to a lack of
demonstrated HCV treatment options for this group.

About Grazoprevir/Elbasvir

Grazoprevir/elbasvir is an investigational, once-daily single tablet
regimen consisting of grazoprevir (NS3/4A protease inhibitor) and
elbasvir (NS5A replication complex inhibitor). As part of Merck’s broad
clinical trials program, grazoprevir/elbasvir is being studied in
multiple HCV genotypes and in patients with difficult-to-treat
conditions such as HIV/HCV co-infection, advanced chronic kidney
disease, inherited blood disorders, liver cirrhosis and those on opiate
substitution therapy.

Merck’s Commitment to HCV

For nearly 30 years, Merck has been at the forefront of the response to
the HCV epidemic. Merck employees are dedicated to applying their
scientific expertise, resources and global reach to deliver innovative
health care solutions that support people living with HCV worldwide.

About Merck

Today’s Merck is 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 www.merck.com
and connect with us on Twitter,
Facebook
and YouTube.

Forward-Looking Statement

This news release 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 Merck’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; Merck’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 Merck patents and other protections
for innovative products; and the exposure to litigation, including
patent litigation, and/or regulatory actions.

Merck undertakes no obligation to publicly update any forward-looking
statement, whether as a result of new information, future events or
otherwise except as required by applicable law. Additional factors that
could cause results to differ materially from those described in the
forward-looking statements can be found in Merck’s 2014 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).

¹ In Phase 2 studies, grazoprevir/elbasvir are administered
as two separate tablets

² Stages 4 and 5 chronic kidney disease are defined as
severely or very severely reduced kidney function, based on estimated
glomerular filtration rate <30 mL/min/1.73m²

³ Includes patients who received ≥1 dose of study drug and
excluded those with missing data because of death or early
discontinuation for reasons unrelated to study drug

Media:
Doris Li, 908-246-5701
or
Sarra Herzog, 201-669-6570
or
Investors:
Joe Romanelli, 908-740-1986
or
Justin Holko, 908-740-1879