Interim Phase II Data of Merck's Investigational MK-5172 in Combination Therapy in Chronic Hepatitis C Virus Genotype 1

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 
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 rateswith 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 development. 
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 
treatment. 
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 RNA. 
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
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the safe harbor provisions of the United States Private Securities Litigation 
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under license. 
References 
___________________
(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, 2012. 
(4) Canadian Liver Foundation. http://www.liver.ca/Liver_Disease/. Accessed 
October 31, 2012. 
Media Contacts: 
Sheila Murphy Merck 514-428-2748 sheila.murphy@merck.com  
Julia Miller Edelman 416-849-2996 julia.miller@edelman.com 
SOURCE: MERCK 
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