Merck Announces Results from Studies Evaluating Investigational Hepatitis C Treatments, MK-5172 and MK-8742, in Treatment-Naïve

  Merck Announces Results from Studies Evaluating Investigational Hepatitis C
  Treatments, MK-5172 and MK-8742, in Treatment-Naïve Patients with Genotype 1
  Infection

          Clinical Findings Support Advancement into Phase 3 Trials

Business Wire

WHITEHOUSE STATION, N.J. -- April 10, 2014

Merck (NYSE:MRK), known as MSD outside of the United States and Canada, today
announced additional data from the ongoing C-WORTHy study, a multi-arm Phase 2
clinical trial evaluating the efficacy and safety of a once-daily, all-oral
regimen combining MK-5172, an investigational hepatitis C virus (HCV) NS3/4A
protease inhibitor, and MK-8742, an investigational HCV NS5A replication
complex inhibitor, among patients with chronic HCV Genotype 1 infection (GT1).
In an interim analysis of treatment-naïve, non-cirrhotic patients administered
a 12-week regimen of MK-5172/MK-8742, with and without ribavirin (RBV), a
sustained viral response^1 (SVR) was observed in 98 percent (42/43) of
patients administered MK-5172/MK-8742 alone and 94 percent (75/80) in those
administered MK-5172/MK-8742 plus RBV. These data were presented, along with
data on an 8-week regimen, at the 49th Annual Meeting of the European
Association for the Study of the Liver (EASL), also known as The International
Liver Congress™ 2014, in London, UK.

“These Phase 2 results add to growing evidence for the potential efficacy of
MK-5172 and MK-8742 for treatment of chronic HCV infection,” said Dr. Eliav
Barr, vice president, Infectious Diseases, Merck Research Laboratories. “These
findings are integral to advancing our research of these investigational
candidates into C-EDGE, the Phase 3 clinical program that will seek to more
broadly evaluate the potential of MK-5172/MK-8742 in diverse patient
populations.”

C-WORTHy Study Design

C-WORTHy is a two-part, parallel-group, randomized (within group) clinical
trial evaluating a range of subpopulations of patients with HCV GT1 infection.
The study evaluated different treatment durations of MK-5172 (100 mg once
daily) plus MK-8742 (50 mg once daily), with or without RBV. A total of 471
patients with HCV GT1 RNA levels of ≥10,000 IU/mL were enrolled in C-WORTHy
across 16 arms.

Key Findings for MK-5172/MK-8742

The interim results presented were from treatment-naïve, non-cirrhotic
patients who received one of 3 regimens: A) MK-5172/MK-8742 + RBV for 8 weeks
(N=30), B) MK-5172/MK-8742 + RBV for 12 weeks (N=85), and C) MK-5172/MK-8742
(without RBV) for 12 weeks (N=44), (see table 1).

Table 1 – Interim Results from the C-WORTHy Trial Showing Treatment-Naïve,
Non-Cirrhotic Patients with HCV GT1 Infection (Intention-to-Treat (ITT)
Analysis)

                                                           
                            MK-5172 +           MK-5172 +           MK-5172 +
                            MK-8742             MK-8742 +           MK-8742 +
Parameter                 (NO RBV)          RBV               RBV
                            (12 Weeks)          (12 Weeks)          (8 Weeks)
                            (N =44)             (N = 85)            (N =30)
SVR4-24^†, % (n)          98% (43)          94% (80)          83% (25)
No SVR, % (n)
Breakthrough              0                 1% (1)            0
Relapse                   2% (1)            1% (1)            17% (5)
Non-virologic             0                 4% (3)            0
Discontinuation
By Sub-genotype
GT1a                      97% (29)          94% (49)          83% (25)
GT1b^§                    100% (14)         94% (31)          --
† Part A: 100% of patients completed Follow-up week (FU)24; Part B: 8 week
arm: 93% have completed FU8; 12 week arm: 100% of patients have completed FU4;
2 patients (Part A) and 1 patient (Part B) discontinued early and are counted
as failures.

§ Two patients with GT1 (non-a, non-b) were enrolled; these are analyzed with
GT1b.

Among the five patients who relapsed in the eight-week regimen arm of PN035B,
two patients had very low MK-5172 and MK-8742 levels during the course of
therapy. The relationship between this finding and the relapse is being
investigated.

The most common adverse events recorded in the RBV and RBV-free treatment
groups, respectively, were fatigue (32%, 23%), headache (20%, 33%), nausea
(21%, 16%), diarrhea (13%, 9%) and insomnia (13%, 7%). There were no early
discontinuations due to drug-related adverse events and no clinically
significant abnormalities detected in routine laboratory analysis of
hematologic markers.

PN038 Study Design and Findings

Additionally, new data from PN038, a Phase 2 dose-ranging clinical trial
evaluating MK-5172 once-daily with peginterferon alfa-2b and ribavirin (PR,
weekly), were presented, evaluating SVR24 in treatment-naïve, non-cirrhotic
patients with GT1 infection. PN038 is  a Phase 2 clinical trial investigating
the efficacy and safety of MK-5172 doses (25 mg, 50 mg, and 100 mg) once-daily
with PR over a 12-week treatment cycle in GT1 treatment-naïve, non-cirrhotic
patients (n=87). The analysis presented was ITT, in which all patients who did
not achieve SVR (including those who dropped out for non-virologic reasons),
were recorded as failures.

MK-5172 at doses of 50 mg and 100 mg with PR for 12 weeks of treatment
achieved SVR24 rates of 75.0 percent (21/28) and 83.3 percent (25/30),
respectively, supporting use of MK-5172 below 100 mg dose (see table 2).

Table 2: PN038 Virologic Responses – (ITT Analysis)


Patients with HCV RNA <25 IU/mL / total # of patients (%)
            MK-5172 25 mg       MK-5172 50 mg       MK-5172 100 mg
        with PR          with PR          with PR
            (N=29)              (N=28)              (N=30)
TW*4     93.1% (27/29)    96.4% (27/28)    100.0% (30/30)
TW12     93.1% (27/29)    96.4% (27/28)    96.7% (29/30)
SVR12    48.3% (14/29)    75.0% (21/28)    86.7% (26/30)
SVR24    48.3% (14/29)    75.0% (21/28)    83.3% (25/30)

*Treatment week

The most common recorded adverse experiences recorded across all treatment
arms were: fatigue (61%), headache (46%), nausea (43%), and decreased appetite
(43%). These adverse experiences did not appear to be dose-related.

One patient discontinued therapy after seven days of dosing with MK-5172 100
mg, plus PR and experienced muscle inflammation (creatine kinase >5x upper
limits of normal [ULN]), elevated transaminases to >3x ULN, and total
bilirubin >2x ULN, associated with a positive toxicology screen for ethanol.
There were no other clinically significant transaminase elevations recorded in
this study.

About Merck’s Phase 3 HCV Program: C-EDGE

Based on the results of the Phase 2 clinical program, Merck has initiated
Phase 3 clinical trials for MK-5172/MK-8742. The Phase 3 program, called
C-EDGE, will evaluate the safety and efficacy of MK-5172/MK-8742 with and
without ribavirin in various genotypes and across a broad range of patient
populations with chronic HCV. Study cohorts will include: C-EDGE TN (GT1,
GT4-6; treatment-naive ± cirrhosis), C-EDGE CO-INFXN (GT1, GT4-6;
treatment-naive ± cirrhosis with HIV/HCV co-infection), C-EDGE RECOVERY (GT1,
GT4-6; treatment-naive ± cirrhosis; ± HIV/HCV co-infection on opiate
substitution therapy), and C-EDGE TE (GT1, GT4-6; prior failed treatment with
peginterferon/ribavirin; ± HIV/HCV co-infection). Study information can be
found at www.clinicaltrials.gov.

Merck’s Commitment to HCV

For more than 25 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 healthcare solutions that
support people living with HCV worldwide.

About Merck

Today's Merck is a global healthcare leader working to help the world be well.
Merck is known as MSD outside of the United States and Canada. Through our
prescription medicines, vaccines, biologic therapies, and consumer care 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 healthcare through far-reaching policies,
programs and partnerships. For more information, visit www.merck.com and
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Merck 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. 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’s
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.
Additional factors that could cause results to differ materially from those
described in the forward-looking statements can be found in Merck’s 2013
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 Defined as HCV RNA below the limit of quantification or below the limit of
detection at the last visit on record – 4, 8, 12, or 24 weeks after the
completion of therapy

Contact:

Merck
Media:
Caroline Lappetito, 267-305-7639
Sarra Herzog, 201-669-6570
or
Investors:
Carol Ferguson, 908-500-1101
Justin Holko, 908-423-5088
 
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