Final Results from the C-WORTHy Study (Parts
A and B) Presented at The Liver Meeting® and Published in
The Lancet
First Wave of Phase 3 Development Program
for Grazoprevir/Elbasvir is Fully Enrolled; Merck Plans to Submit
New Drug Application in 2015
Merck (NYSE:MRK), known as MSD outside the United States and
Canada, today announced the presentation of results from a
multi-arm Phase 2 clinical trial evaluating grazoprevir/elbasvir
(MK-5172/MK-8742, the company’s investigational NS3/4A protease
inhibitor and NS5A inhibitor, respectively) with or without
ribavirin (RBV) in treatment-naïve and previously-treated (with
peg-interferon/ribavirin [PR]) patients with chronic hepatitis C
virus (HCV) genotype 1 (GT1) infection -- the C-WORTHy study (Parts
A and B). The final results were presented in oral sessions at the
65th American Association for the Study of Liver Diseases (AASLD)
Annual Meeting (also known as The Liver Meeting®) and published as
separate papers online in The Lancet.
“Merck is committed to developing an efficacious, well-tolerated
therapy suitable for a broad spectrum of patients with HCV,” said
Dr. Eliav Barr, vice president, infectious diseases, Merck Research
Laboratories. “We are encouraged by the findings for
grazoprevir/elbasvir in the C-WORTHy trial and look forward to
advancing our broad Phase 3 program, which includes hard-to-cure
patients that are of the highest need and least studied to
date.”
Interim results from the C-WORTHy study were presented in April
2014 at the 49th Annual Meeting of the European Association for the
Study of the Liver (EASL) and announced by Merck.
Results for Treatment-Naïve Cirrhotic Patients and PR
Null-Responders
The results for HCV mono-infected treatment-naïve GT1 patients
with cirrhosis and GT1 prior null-responders with or without
cirrhosis treated with grazoprevir/elbasvir, with or without
ribavirin, for 12 weeks or 18 weeks are shown in table 1. The rates
of sustained viral response,i 12 weeks after the completion of
therapy (SVR12) were greater than, or equal to, 90 percent
regardless of treatment duration or co-administration of RBV.
Table 1
Grazoprevir/ Elbasvir
Treatment Duration (wks)
Treatment-Naïve Patientswith
Cirrhosis
PR-NullsWith or Without
Cirrhosis
12 18 12 18
RBV +RBV -RBV +RBV -RBV + RBV
- RBV +RBV -RBV SVR12, n/N Percent [95% CI]
28/3190%[74, 98]
28/2997%[82,100]
31/32*97%[84,100]
29/3194%[79, 99]
30/32*94%[79, 99]
30/3391%[76, 98]
33/33100%[89, 100]
31/3297%[84, 100]
iiVirologic Failure 3† 1 0 2 0
3 0 1†
*1 treatment-naïve patient and 2 PR-null
patients were lost to follow-up.
†Virologic breakthrough was seen in 1
treatment-naïve patient in the 12-wk +RBV group and in one PR-null
patient in the 18-wk -RBV.
The rate of virologic failure was five percent (6/123) in
treatment-naïve cirrhotic patients and three percent (4/130) in the
null-responder population. Treatment was generally well-tolerated.
The most common adverse events associated with the administration
of grazoprevir/elbasvir in combination with or without RBV were:
fatigue (26%), headache (23%) and asthenia (14%). There were no
early discontinuations due to adverse events with
grazoprevir/elbasvir and no clinically significant abnormalities
observed in routinely evaluated biomarkers.
Results for HCV Mono-Infected and HIV/HCV Co-Infected
Patients
Treatment-naïve, non-cirrhotic mono-infected GT1 patients and
non-cirrhotic HCV GT1 /HIV co-infected patients treated for 12
weeks with grazoprevir/elbasvir with or without RBV, demonstrated
high rates of SVR12, as seen in table 2. Among this patient
population treated for 12 weeks, the overall rate of virologic
failure was four percent (7/188), including three breakthrough
failures and four relapses, in both mono- and co-infected patients.
In patients treated for eight weeks, the rate of virologic failure
was 17 percent (5/30), with five relapses. The most common adverse
events with or without RBV were fatigue (23%), headache (20%),
nausea (15%) and diarrhea (10%). There were no early
discontinuations due to adverse events with grazoprevir/elbasvir
and no clinically significant abnormalities observed in routinely
evaluated biomarkers.
Table 2
Grazoprevir/ ElbasvirTreatment Duration
(wks)
HCV Mono-infected HIV/HCV Co-infected
8*** 12 12
12 12 RBV +RBV +RBV -RBV
+RBV -RBV
SVR12 (n/m)
[95% confidence interval]
80% (24/30*)[61, 92]
93% (79/85*)[85, 97]
98% (43/44)[88, 100]
97% (28/29)[82, 100]
87% (26/30*)[69, 96]
iiVirologic Failure 5 3**† 1 1 2
* 4 HCV mono-infected patients (1 in the
8-wk and 3 in the 12-wk +RBV arms) and 2 HIV/HCV co-infected
patients in the -RBV arm were lost to follow-up.
**Virologic breakthrough was seen in 1
patient, which was a new infection with HCV GT2b (or a minor GT2b
variant at baseline).
***GT1a patients only.
†1 of the patients who relapsed did not
receive grazoprevir and received only elbasvir plus RBV for the
first month of treatment.
About the C-WORTHy Study
C-WORTHy is a randomized, dose response, parallel-group,
multiple-site, double-blind clinical trial comparing diverse
patient populations exposed to different durations of treatment of
grazoprevir/elbasvir with or without RBV in patients with chronic
HCV infection. In C-WORTHy Parts A and B, a total of 471 patients
with chronic HCV GT1 infection with HCV RNA levels of ≥10,000 IU/mL
were enrolled and randomized across 16 arms. The patients include
hard-to-cure sub-populations, including treatment-naïve patients
with liver cirrhosis (12- and 18-week arms, with and without RBV)
and prior-null responder patients with and without cirrhosis (12-
and 18-week arms, with and without RBV). The lead authors of The
Lancet publications and presenters at The Liver Meeting® are Dr.
Eric Lawitz of The Texas Liver Institute and professor of medicine
at The University of Texas Health Science Center, San Antonio, TX
(C-WORTHy Cirrhotic Patients and Prior Null-Responders); and Dr.
Mark Sulkowski, professor of medicine at The Johns Hopkins
University School of Medicine, Baltimore, MD (C-WORTHy HCV
Mono-Infected and HIV/HCV Co-Infected Patients).
About C-EDGE: Merck’s Phase 3 HCV Program
The results of the C-WORTHy study supported the advancement of
grazoprevir/elbasvir into the Phase 3 clinical development program
called C-EDGE. The Phase 3 C-EDGE program is evaluating
grazoprevir/elbasvir with and without RBV in various genotypes and
across a broad range of patient populations with chronic HCV
infection, including treatment-naive patients and patients who
previously failed PR therapy, patients with and without cirrhosis,
patients with chronic kidney disease (including those on
hemodialysis), patients with HIV/HCV co-infection, patients on
opiate substitution therapy and patients with inherited blood
disorders. Merck initiated the first C-EDGE study in April 2014,
and the grazoprevir/elbasvir registration studies within the C-EDGE
program – including C-EDGE TN (treatment-naïve), C-EDGE CO-INFXN
(HIV/HCV co-infected) and C-EDGE TE (treatment-experienced) -- are
now fully enrolled. Results from these trials are anticipated in
the first half of 2015. Learn more at
http://www.merck.com/clinical-trials/.
About Grazoprevir/Elbasvir
Grazoprevir/elbasvir (MK-5172/MK-8742) is an investigational,
oral, once-daily, fixed-dose combination chronic HCV treatment,
consisting of grazoprevir, an investigational oral, once-daily HCV
NS3/4A protease inhibitor, and elbasvir, an investigational oral,
once-daily HCV NS5A replication complex inhibitor. In October 2013,
Merck announced that the U.S. Food and Drug Administration (FDA)
granted Breakthrough Therapy designation to grazoprevir/elbasvir
for treatment of chronic HCV infection. 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. Merck plans to submit the
New Drug Application for grazoprevir/elbasvir in 2015.
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 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 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 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 healthcare
legislation in the United States and internationally; global trends
toward healthcare 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).
i 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.ii Virologic failure is
the inability to achieve or maintain suppression of viral
replication to an HCV RNA level <200 copies/mL.
MerckMedia:Pam Eisele, 267-305-3558Sarra Herzog,
201-669-6570orInvestors:Joe Romanelli, 908-423-5185Justin Holko,
908-423-5088
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