Last updated on April 24, 2014 at 6:42 EDT

Interim Phase II Data of Merck’s Investigational MK-5172 in Combination Therapy in Chronic Hepatitis C Virus Genotype 1 Infection to be Presented at the American Association for the Study of Liver Diseases (AASLD) Annual Meeting

November 10, 2012

BOSTON, MA, Nov. 10, 2012 /CNW/ – Merck announced interim results from a
Phase II, multi-center, randomized, dose-ranging study (n=332)
assessing the safety and antiviral activity of MK-5172, an
investigational, once-daily, oral NS3/4A protease inhibitor for the
treatment of chronic hepatitis C virus (HCV) genotype 1 infection in
combination therapy in treatment-naïve patients. These data will be
presented this week at The American Association for the Study of Liver
Diseases (AASLD) 2012 Annual Meeting.

The primary efficacy endpoint of the study was to evaluate the complete
early viral response (cEVR) of four regimens of MK-5172 in combination
with peginterferon alfa-2b and ribavirin (P/R) compared to the control
arm in which patients received a 4-week lead-in of P/R followed by the
addition of boceprevir (VICTRELIS(TM)). cEVR was assessed by the proportion of patients who achieved
undetectable virus (HCV RNA) at week 12 and at week 16 in the control. 
The MK-5172 regimens had rates of cEVR that ranged from 82.8 to 93
percent, versus the control rate of 74.2 percent.

“These initial results are promising as they show we increased viral
eradication rates with MK-5172, said Alnoor Ramji, M.D., Clinical
Assistant Professor at the University of British Columbia and a study
investigator.” At present, we will continue to treat persons with
genotype 1 hepatitis C with standard of care triple therapy given the
already high eradication rates we can achieve.  Future therapies, such
as MK-5172, may offer higher eradication rates, be better tolerated and
have easier dosing schedules, however, it will be sometime before they
will be available in Canada.”

In the initial cohort, termed the “Vanguard Cohort,” (n=136), 96 percent
of patients (25/26) who received a regimen containing 100 mg QD of
MK-5172 with P/R achieved sustained virologic response (SVR) 12,
defined as having undetectable virus (HCV RNA) 12 weeks after treatment
ended, compared to 54 percent of patients (13/24) in the control arm.
Currently planned studies evaluating interferon-free regimens with
MK-5172 will be dosed at 100 mg QD.

“We are excited by these interim results evaluating MK-5172 in
combination therapy,” said Eliav Barr, M.D., Vice President of
Infectious Disease at Merck Research Laboratories.  “Our commitment to
chronic hepatitis C remains steadfast. We look forward to continuing
our studies of MK-5172, including in interferon-free regimens.”

Other data to be presented on MK-5172 at AASLD includes results from a
preclinical study evaluating the antiviral activities of MK-5172 in
combination with MK-8742, an oral HCV NS5A inhibitor in Phase I

Boceprevir in Canada
Boceprevir was approved for use in Canada in July 2011 for the treatment
of chronic hepatitis C genotype 1 infection, in combination with
peginterferon alpha and ribavirin, in adult patients (18 years of age
and older) with compensated liver disease, including cirrhosis, who are
previously untreated or who have failed previous therapy.(1)

Hepatitis C in Canada
An estimated 250,000 individuals in Canada are infected with HCV and
there are 3,200 to 5,000 newly infected individuals each year.(2) HCV damages the liver and may lead to serious complications, including
death, when left untreated.(3) It is the leading cause of liver transplants in Canada.(4)

About the Study
This Phase II, multi-center, double blind, randomized,
active-controlled, dose ranging, response-guided therapy (RGT) study is
designed to examine the safety and antiviral activity of MK-5172
administered with peginterferon alfa-2b (1.5 µg/kg/week) and an
investigational, weight-based dose of ribavirin (600-1,400 mg/day)
(P/R) in non-cirrhotic, treatment-naïve, adult patients with chronic
HCV genotype 1 infection.  In the study, 332 patients were enrolled in
two cohorts: the Vanguard Cohort of 136 patients, followed by a Second
Cohort of 196 patients. In both cohorts, patients were randomized to
one of four MK-5172 treatment arms (100mg QD, 200 mg QD, 400 mg QD, 800
mg QD). All patients received MK-5172 in combination with P/R for 12
weeks followed by P/R for 12 or 36 weeks, depending on treatment
response at treatment week 4. If the patient’s virus (HCV RNA) was
target not detected (TND; <10 IU/mL) at treatment week (TW) 4, then the
patient was able to stop all therapy at TW 24. If the patient’s virus
was target detected unquantifiable (TD(u); <25 IU/mL) or target
detected quantifiable (TD(q)) at TW 4, then the patient stopped all
therapy at TW 48.  In the control arm, patients received a 4-week
lead-in of P/R followed by the addition of boceprevir, administered as
recommended in the prescribing information.

After the primary TW 12 analysis of the MK-5172 arms in the Vanguard
cohort, patients receiving the 400 mg and 800 mg doses in the Second
Cohort were down-dosed due to elevated liver transaminases and began to
receive 100 mg in an open-label fashion between weeks 3 and 12 of
MK-5172 therapy.

All patients in both cohorts of the study (termed the Combined Cohort
when analyzed together) have reached the primary endpoint of the study,
cEVR, or have discontinued early. cEVR values reflect both those
patients with both undetectable (TND) and detectable unquantifiable
(TD(u)) HCV RNA.  In the Second Cohort, 134 of 156 patients randomized
into the MK-5172 arms are receiving P/R (n=17) or are in the follow-up
phase (n=117) of the study. All patients in the Vanguard Cohort who
received MK-5172 are in the follow-up phase of the study or have
discontinued early.

Of the patients randomized to the MK-5172 arms, 2.3 percent (6/266) met
the protocol-defined criteria for virologic failure: one (1) patient
was re-infected with genotype 3 infection; and four patients had no
detectable (n=3) or low (n=1) levels of MK-5172 at time of failure and
for a period of time prior.  The primary efficacy analysis included the full analysis set (FAS) of
all randomized patients who received at least one dose of study

SVR12 Results in the Vanguard Cohort
In the Vanguard Cohort, higher SVR12 rates were achieved across all
MK-5172 arms compared to control (FAS) – 96.2 percent (25/26) in the
MK-5172 100 mg arm; 86.7 percent (26/30) in the MK-5172 200 mg arm;
87.0 percent (20/23) in the MK-5172 400 mg arm; and 81.5 percent
(22/27) in the MK-5172 800 mg arm; versus 54.2 percent (13/24) in the
control arm. All patients achieving SVR12 had undetectable (TND) HCV

Safety Findings
In the MK-5172 arms of the study, there were two transient liver
abnormalities observed – elevations in bilirubin before TW4, associated
with normalization of ALT/AST levels, and elevations in liver
transaminases (ALT/AST) occurring after TW4.

Of those patients with bilirubin elevation, 92 percent (22/24) occurred
within the first seven to 23 days of therapy, and their bilirubin
levels decreased from peak levels despite continued dosing.

The frequency and severity of ALT/AST elevations were dose dependent.
The frequencies of ALT/AST elevations in the MK-5172 100 mg arm and the
control arm after TW4 were comparable at 2 percent each, (1/66) and
(1/66), respectively.  The frequency of ALT/AST elevations observed in
the MK-5172 200 mg, MK-5172 400 mg and MK-5172 800 mg arms after TW 4
were higher.  One patient in the MK-5172 800 mg arm experienced a
serious adverse event due to elevated ALT and bilirubin levels, which
returned to normal after stopping therapy.

About MK-5172
MK-5172 is an investigational, once-daily, oral HCV NS3/4A protease
inhibitor currently in Phase II development that has demonstrated
potent in vitro antiviral activity.  Early data on MK-5172 has shown a
broad HCV genotypic activity spectrum and in vitro activity against
genotype 1a and 1b viral variants that have been associated with
resistance to other HCV protease inhibitors, including those in
development.  Given the clinical experience of MK-5172 to date,
including its potentially high barrier to resistance and antiviral
activity across HCV genotypes, Merck will evaluate MK-5172 in treatment
regimens in a broad spectrum of patients with chronic HCV infection.

Merck recently announced plans to initiate two new clinical trials
designed to assess the efficacy and safety of MK-5172 in all-oral,
interferon-free combination regimens in non-cirrhotic, treatment-naïve
patients with chronic HCV genotype 1 infection.  More information is
available at http://clinicaltrials.gov using identifiers, NCT01717326 and NCT01716156.

Merck’s Global Commitment to Advancing Hepatitis Therapy
Merck is committed to building on its strong legacy in the field of
viral hepatitis by continuing to discover, develop and deliver vaccines
and medicines to help prevent and treat viral hepatitis. In hepatitis C, company researchers developed the first approved therapy
for chronic HCV in 1991 and the first combination therapy in 1998. In
addition to ongoing studies with VICTRELIS(TM), extensive research efforts are underway to develop additional
innovative oral therapies for viral hepatitis treatment.

About Merck
Today’s Merck is a global healthcare leader working to help the world be
well.  Merck is known as MSD outside the United States and Canada.
Through our medicines, vaccines, biologic therapies, and consumer and
animal 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 healthcare through far-reaching
policies, programs and partnerships. For more information about our
operations in Canada, visit www.merck.ca.

Forward-Looking Statement
This news release includes “forward-looking statements” within the
meaning of the safe harbor provisions of the United States Private
Securities Litigation Reform Act of 1995. Such statements may include,
but are not limited to, statements about the benefits of the merger
between Merck and Schering-Plough, including future financial and
operating results, the combined company’s plans, objectives,
expectations and intentions and other statements that are not
historical facts. Such statements are based upon the current beliefs
and expectations of Merck’s management and are subject to significant
risks and uncertainties. Actual results may differ from those set forth
in the forward-looking statements.

The following factors, among others, could cause actual results to
differ from those set forth in the forward-looking statements: the
possibility that all of the expected synergies from the merger of Merck
and Schering-Plough will not be realized, or will not be realized
within the expected time period; the impact of pharmaceutical industry
regulation and health care legislation in the United States and
internationally; Merck’s ability to accurately predict future market
conditions; dependence on the effectiveness of Merck’s patents and
other protections for innovative products; and the exposure to
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. Additional factors that could cause results to differ
materially from those described in the forward-looking statements can
be found in Merck’s 2011 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).

(TM) Trademark of Schering Corporation, a subsidiary of Merck & Co., Inc. Used under license.

(1) VICTRELIS(TM) Product Monograph, July 27, 2011, p. 3.

(2) Canadian Institutes of Health Research. About the Hep C Research
Initiative. http://www.cihr-irsc.gc.ca/e/38855.html. Accessed October 31, 2012.

(3) Public Health Agency of Canada. http://www.phac-aspc.gc.ca/hepc/pubs/multiling-hepc/index-eng.php.
Accessed October 31,

(4) Canadian Liver Foundation. http://www.liver.ca/Liver_Disease/. Accessed October 31, 2012.


Source: PR Newswire