Merck to Release Findings from Integrated Analysis of Six Phase 2 and 3 Clinical Trials Evaluating Investigational Elbasvir/Grazoprevir in Patients with Chronic Hepatitis C Genotype 1, 4 or 6 Infection and Compensated Cirrhosis at The Liver Meeting®
November 15, 2015 12:00 am ET
Patients with Compensated Liver Cirrhosis Among Most Difficult-to-Treat
KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced the presentation of results from an integrated analysis
of patients with compensated liver cirrhosis (Child-Pugh class A) from
six Phase 2 and 3 clinical trials evaluating the efficacy and safety of
the investigational once-daily tablet elbasvir/grazoprevir1
(50mg/100mg) with or without ribavirin (RBV) in patients with chronic
hepatitis C virus (HCV) genotypes (GT) 1, 4 or 6 infection. Results from
the full analysis set (FAS) (n=402) demonstrate that treatment-naïve
patients with compensated liver cirrhosis who received
elbasvir/grazoprevir with or without RBV for 12 weeks achieved sustained
virologic response 12 weeks after the completion of treatment (SVR12, or
virologic cure) at rates of 90 percent (28/31) and 98 percent (135/138),
respectively. Treatment-experienced patients who received
elbasvir/grazoprevir with or without RBV for 12 weeks achieved virologic
cure rates of 91 percent (74/81) and 89 percent (48/54), respectively.
Treatment-experienced patients who received elbasvir/grazoprevir with or
without RBV for 16 or 18 weeks achieved virologic cure rates of 100
percent (49/49) and 94 percent (46/49), respectively. These data will be
presented during an oral presentation at The
Liver Meeting® (Abstract #42).
“Patients with chronic hepatitis C virus infection and compensated
cirrhosis have historically been difficult to treat because their
bodies’ ability to respond to antiviral therapy is compromised,” said
Dr. Ira Jacobson, site chair, department of medicine, Mount Sinai Beth
Israel, New York. “In this integrated analysis of data from multiple
trials, patients treated with elbasvir/grazoprevir were able to achieve
high virologic cure rates, often without the addition of ribavirin.”
The integrated analysis included patients with compensated liver
cirrhosis (Child-Pugh class A) from six Phase 2 and 3 clinical trials,
the individual results of which have been previously presented: C-WORTHy,
TE and C-SALVAGE.
The analysis evaluated the efficacy and safety of investigational
once-daily elbasvir/grazoprevir with or without RBV for 12 weeks in
treatment-naïve patients (n=169) and 12 and 16 or 18 weeks in
treatment-experienced patients (n=233). Of the treatment-experienced
patients, 64 percent (150/233) were prior non-responders, 21 percent
(49/233) were prior relapsers and 15 percent (34/233) were previously
treated with HCV NS3/4A protease inhibitors (simeprevir, telaprevir and
Two sets of patients were analyzed. In the FAS, the assessment included
all randomized patients who received at least one dose of drug (n=402).
The integrated analysis also assessed a modified full analysis set
(mFAS) (n=398) that excluded four patients who discontinued treatment
for reasons unrelated to the study drug: one treatment-naïve patient on
12 weeks of elbasvir/grazoprevir without RBV; two treatment-experienced
patients on 12 weeks of elbasvir/grazoprevir without RBV; and one
treatment-experienced patient on 12 weeks of elbasvir/grazoprevir with
RBV. Compensated cirrhosis was determined by one of the following
methods: liver biopsy, FibroScan, AST to platelet ratio or FibroTest.
Summary of SVR12 Findings: FAS
|12||12||12||12||16 or 18||16 or 18|
* Virologic failure occurred in one percent (2/138) of patients
including one breakthrough and one relapse.
† Virologic failure occurred in 10 percent (3/31) of patients
including one breakthrough and two relapses.
§ Virologic failure occurred in seven percent (4/54) of
patients including four relapses.
‡ Virologic failure occurred in seven percent (6/81) of
patients including six relapses.
# Virologic failure occurred in six percent (3/49) of
patients including two rebounds and one relapse.
Summary of SVR12 Findings: mFAS2
|Without RBV (n=137)*|
|All Patients||99% (135/137)**|
* In the additional population of treatment naïve patients administered
elbasvir/grazoprevir with RBV for 12 weeks, 90% (28/31) achieved SVR12.
** Virologic failure occurred in one percent (2/137) of patients
including one breakthrough and one relapse.
|Without RBV (n=52)*||With RBV (n=49)**|
|Duration (Weeks)||12||16 or 18|
|All Patients||92% (48/52)***||100% (49/49)|
† Prior null response, partial response or relapse with pegylated
* In the additional population of treatment-experienced patients
administered elbasvir/grazoprevir with RBV for 12 weeks, 93% (74/80)
** In the additional population of treatment-experienced patients
administered elbasvir/grazoprevir without RBV for 16 or 18 weeks, 94%
(46/49) achieved SVR12.
*** Virologic failure occurred in eight percent (4/52) of patients
including four relapses.
The most common adverse events (AEs) reported in patients who received
elbasvir/grazoprevir, or elbasvir/grazoprevir with RBV, and placebo
were: fatigue (15%, 31% and 18%, respectively), headache (17%, 21% and
14%, respectively) and nausea (4%, 14% and 14%, respectively). One
serious drug-related AE occurred in a patient taking
elbasvir/grazoprevir due to severe abdominal pain without associated
symptoms. Seven patients discontinued due to treatment-related AEs (two
patients taking elbasvir/grazoprevir; four patients taking
elbasvir/grazoprevir with RBV; and one patient taking placebo).
Elbasvir/grazoprevir is Merck’s investigational, once-daily, fixed-dose
combination therapy containing elbasvir (HCV NS5A replication complex
inhibitor) and grazoprevir (HCV NS3/4A protease inhibitor). Merck’s
broad clinical trials program includes evaluations of
elbasvir/grazoprevir with or without ribavirin for multiple HCV
genotypes, together with patients with difficult-to-treat conditions,
such as cirrhosis, advanced chronic kidney disease, HIV/HCV
co-infection, inherited blood disorders and those on opioid agonist
therapy. In July 2015, the U.S. Food and Drug Administration (FDA)
granted Priority Review for the New Drug Application for
elbasvir/grazoprevir with a Prescription Drug User Fee Act (PDUFA)
action date of Jan. 28, 2016.
In April 2015, the FDA granted Breakthrough Therapy Designation for
elbasvir/grazoprevir for the treatment of patients with chronic HCV GT1
infection with end stage renal disease on hemodialysis, and Breakthrough
Therapy Designation for elbasvir/grazoprevir for the treatment of
patients with chronic HCV GT4 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
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.
Today’s Merck is a global health care 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 health care through
far-reaching policies, programs and partnerships. For more information,
and connect with us on Twitter,
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1 Elbasvir is an HCV NS5A replication complex inhibitor and
grazoprevir is an HCV NS3/4A protease inhibitor.
2 Data presented in Tables 2a and 2b include regimens by
treatment population with the highest rates of SVR or comparable SVR
without the addition of RBV.
Doris Li, 908-246-5701
Sarra Herzog, 201-669-6570
Teri Loxam, 908-740-1986
Justin Holko, 908-740-1879