Clinical Findings Support Advancement into
Phase 3 Trials
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 response1 (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)
Parameter MK-5172 +
MK-8742(NO RBV)(12 Weeks)(N =44)
MK-5172 + MK-8742 + RBV(12 Weeks)(N =
85) MK-5172 + MK-8742 +RBV(8
Weeks)(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
Discontinuation 0 4%
(3) 0 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 with
PR(N=29) MK-5172 50 mg
with PR (N=28) MK-5172 100
mg with PR(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 connect with us on Twitter, Facebook and
YouTube.
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
MerckMedia:Caroline Lappetito, 267-305-7639Sarra Herzog,
201-669-6570orInvestors:Carol Ferguson, 908-500-1101Justin Holko,
908-423-5088
Merck (NYSE:MRK)
Historical Stock Chart
From Mar 2024 to Apr 2024
Merck (NYSE:MRK)
Historical Stock Chart
From Apr 2023 to Apr 2024