In Phase 3 Clinical Trials, ZEPATIER
Achieved High Cure (SVR) Rates Across Diverse Populations of
Patients With Chronic Hepatitis C, Including Those With Compensated
Cirrhosis, Renal Impairment or on Opioid Agonist Therapy
MSD (tradename of Merck & Co., Inc., Kenilworth, N.J., USA
(NYSE: MRK)) today announced that the European Commission has
approved ZEPATIER™ (elbasvir/grazoprevir) with or without ribavirin
(RBV) for the treatment of chronic hepatitis C virus (HCV) genotype
(GT) 1 or GT4 infection in adults. ZEPATIER is MSD’s once-daily,
fixed-dose combination tablet containing the NS5A inhibitor
elbasvir (50mg) and the NS3/4A protease inhibitor grazoprevir
(100mg). This approval allows marketing of ZEPATIER tablets in the
28 countries that are members of the European Union, as well as
European Economic Area members, Iceland, Liechtenstein and Norway.
MSD continues to work to supply the EU market, with product
launches estimated to begin between the fourth quarter of 2016 and
the first quarter of 2017. Product launches are expected to
continue across the EU through 2017.
“The approval of ZEPATIER in the European Union, following
approvals in the United States and Canada earlier this year, is an
important step in offering a new and effective treatment for
millions of people infected with hepatitis C virus genotype 1 or
4,” said Dr. Roger M. Perlmutter, president, Merck Research
Laboratories, a U.S.-based division of Merck & Co., Inc.,
Kenilworth, N.J., USA. “ZEPATIER is the most recent advance from
MSD in our more than 30-year effort to combat the effects of
hepatitis C virus infection, and hence, to reduce the burden of
this disease around the world.”
Thousands of chronic HCV patients worldwide participated in the
ZEPATIER clinical development program, which was designed to
include patients with known treatment challenges, such as those
with compensated cirrhosis and those for whom treatment with
peginterferon plus RBV, with or without an HCV protease inhibitor,
has not worked. In the trials, overall sustained virologic response
(SVR) 12 weeks after the completion of therapy (SVR12, considered
virologic cure based on undetectable HCV RNA levels) was achieved
in 96 percent (301/312) of chronic HCV GT1b-infected patients
treated with ZEPATIER for 12 weeks. In chronic HCV GT1a-infected
patients, 93 percent (483/519) and 95 percent (55/58) achieved cure
following treatment with ZEPATIER for 12 weeks or ZEPATIER plus RBV
for 16 weeks, respectively. Additionally, 94 percent (61/65) and
100 percent (8/8) of chronic HCV GT4-infected patients achieved
cure following treatment with ZEPATIER for 12 weeks or ZEPATIER
plus RBV for 16 weeks, respectively.
Chronic HCV infection, caused by a blood-borne virus, is a major
public health concern affecting more than 170 million people
globally, 15 million of whom are living in Europe. Of the six
genotypes of chronic HCV infection, GT1 is the most common in
Europe accounting for approximately 66 percent of cases, and GT1b
infection is the most prevalent sub-genotype in the majority of
European countries. In addition, the prevalence of GT4 infection is
increasing in Europe.
“Given the complexities of chronic hepatitis C, it is critical
to have a variety of effective treatment options to ensure diverse
types of patients have the highest possible chance to achieve
cure,” said Professor Rafael Esteban, M.D., chief of the internal
medicine and liver unit of the Hospital Universitario Val d’Hebron,
Barcelona, Spain, and professor of medicine at the Universidad
Autonoma de Barcelona. “In clinical trials, ZEPATIER achieved high
cure rates among a broad range of chronic hepatitis C patients with
genotype 1 or 4 infection, from patients who are treatment-naïve to
many of those whose chronic HCV infection has been historically
difficult-to-treat, providing an important new option in the fight
against this global public health epidemic.”
A 12-week, once-daily regimen is recommended for patients with
chronic HCV GT1 or GT4 infection. For certain patients, a regimen
of ZEPATIER plus RBV for 16 weeks should be considered. The
recommended regimens and durations for treatment with once-daily
ZEPATIER in chronic HCV patients with or without compensated
cirrhosis (Child-Pugh A only) are included in the chart below. No
dose adjustments are required when using ZEPATIER with
acid-reducing agents.
HCV Genotype Treatment and Duration GT1a
ZEPATIER for 12 weeks
ZEPATIER for 16 weeks plus RBV* should be
considered in patientswith baseline HCV RNA level >800,000 IU/ml
and/or the presence of specific NS5Apolymorphisms‡ to minimise the
risk of treatment failure.
GT1b ZEPATIER for 12 weeks GT4
ZEPATIER for 12 weeks
ZEPATIER for 16 weeks plus RBV* should be
considered in patients withbaseline HCV RNA level >800,000 IU/ml
to minimise the risk of treatment failure.
*In the clinical studies, the dose of RBV
was weight-based (<66 kg = 800 mg/day, 66 to 80 kg =
1,000mg/day, 81 to 105 kg = 1,200 mg/day, >105 kg = 1,400
mg/day) administered in two divided doses withfood.
‡NS5A polymorphisms, causing at least a
5-fold reduction in activity of elbasvir, included
L/M28T/A,R/Q30E/H/R/G/K/L/D, L31M/V/F, H58D and Y93C/H/N.
“Expanding the treatment landscape is always meaningful for the
patient community as we continue to build upon the strides made in
recent years to raise awareness of and treat chronic hepatitis C
worldwide,” said Charles Gore, president, World Hepatitis Alliance.
“Competition helps fuel dialogue and ensure people know chronic
hepatitis C is treatable. With new treatment options, more patients
may be able to achieve cure, and hopefully share their stories to
inspire others to get treated.”
ZEPATIER Clinical Trial Program
The efficacy and safety of ZEPATIER were evaluated in eight
clinical studies in approximately 2,000 patients. The development
program was designed to investigate ZEPATIER across diverse chronic
HCV patients, including those on opioid agonist therapy, with
chronic kidney disease or with HCV/HIV-1 co-infection. The primary
efficacy endpoint in all studies was SVR12. An overview of the
studies is provided below. For full study details, see the Summary
of Product Characteristics
at http://ec.europa.eu/health/documents/community-register/2016/20160722135308/anx_135308_en.pdf.
Study Patient Population Study Arms
and Duration
C-EDGE TN
(double-blind)
GT1, GT4 or GT6 TN +/-cirrhosis
- ZEPATIER for 12 weeks (N=316)
- Placebo for 12 weeks (N=105)
C-EDGE COINFECTION(open-label)
GT1, GT4 or GT6 TN withHCV/HIV-1
co-infection +/-cirrhosis
- ZEPATIER for 12 weeks (N=218)
C-SURFER
(double-blind)
GT1 TN or TE with Stage 4 orStage 5
chronic kidney disease+/- cirrhosis
- ZEPATIER* for 12 weeks (N=122,including 11 patients in
open-labelintensive PK arm)
- Placebo for 12 weeks (N=113)
C-WORTHY
(open-label)
GT1 or GT3 TN +/- cirrhosis,TE null
responders +/- cirrhosis,
TN with HCV/HIV-1 co-infectionwithout
cirrhosis
- ZEPATIER* for 8, 12 or 18 weeks(N=31, 136 and 63,
respectively)
- ZEPATIER* + RBV† for 8, 12 or 18weeks (N=60, 152 and
65,respectively)
C-SCAPE
(open-label)
GT4 or GT6 TN withoutcirrhosis
- ZEPATIER* for 12 weeks (N=14)
- ZEPATIER* + RBV† for 12 weeks(N=14)
C-EDGE TE
(open-label)
GT1, GT4 or GT6 TE +/-cirrhosis, and +/-
HCV/HIV-1co-infection
- ZEPATIER for 12 or 16 weeks(N=105 and 105, respectively)
- ZEPATIER + RBV† for 12 or 16weeks (N=104 and
106,respectively)
C-SALVAGE
(open-label)
GT1 TE with HCV proteaseinhibitor regimen‡
+/- cirrhosis
- ZEPATIER* + RBV† for 12 weeks(N=79)
C-EDGE
CO-STAR
(double-blind)
GT1, GT4 or GT6 TN on opioidagonist
therapy, +/- cirrhosis
- ZEPATIER for 12 weeks (N=201)
- Placebo for 12 weeks (N=100)
GT = Genotype
TN = Treatment-Naïve
TE = Treatment-Experienced (failed prior
treatment with interferon [IFN] or peginterferon alfa [pegIFN]with
or without RBV or were intolerant to prior therapy)
PK = pharmacokinetic
*Elbasvir 50mg + grazoprevir 100mg
co-administered as single agents
†RBV was administered at a total daily
dose of 800mg to 1,400mg based on weight
‡Failed prior treatment with boceprevir,
telaprevir, or simeprevir in combination with pegIFN + RBV
Important Safety Information about ZEPATIER
(elbasvir/grazoprevir)
ZEPATIER is contraindicated in patients with hypersensitivity to
the active substances or to any of the excipients and in patients
with moderate or severe hepatic impairment (Child-Pugh B or C).
Co-administration of ZEPATIER with inhibitors of organic anion
transporting polypeptide 1B (OATP1B) or with inducers of cytochrome
P450 3A (CYP3A) or p-glycoprotein (P-gp) is also
contraindicated.
The rate of late alanine transaminase (ALT) elevations during
treatment is directly related to the plasma exposure to
grazoprevir. During clinical studies with ZEPATIER with or without
RBV, < 1 % of subjects experienced elevations of ALT from normal
levels to greater than 5 times the upper limit of normal (ULN).
Higher rates of late ALT elevations occurred in females (2 %
[11/652]), Asians (2 % [4/165]), and subjects aged ≥ 65 years (2 %
[3/187]). These late ALT elevations generally occurred at or after
treatment week 8.
Hepatic laboratory testing should be performed prior to therapy,
at treatment week 8, and as clinically indicated. For patients
receiving 16 weeks of therapy, additional hepatic laboratory
testing should be performed at treatment week 12. Patients should
be instructed to consult their healthcare professional without
delay if they have onset of fatigue, weakness, lack of appetite,
nausea and vomiting, jaundice or discoloured faeces.
Discontinuation of ZEPATIER should be considered if ALT levels are
confirmed to be greater than 10 times the ULN. ZEPATIER should be
discontinued if ALT elevation is accompanied by signs or symptoms
of liver inflammation or increasing conjugated bilirubin, alkaline
phosphatase, or international normalised ratio (INR).
ZEPATIER contains lactose monohydrate. Patients with rare
hereditary problems of galactose intolerance, the Lapp lactase
deficiency, or glucose-galactose malabsorption should not take this
medicinal product. ZEPATIER contains 3.04 mmol (or 69.85 mg) sodium
per dose. To be taken into consideration by patients on a
controlled sodium diet.
In clinical studies, the most commonly reported adverse
reactions (greater than 10%) were fatigue and headache. Less than 1
% of subjects treated with ZEPATIER with or without RBV had serious
adverse reactions (abdominal pain, transient ischaemic attack and
anaemia). Less than 1 % of subjects treated with ZEPATIER with or
without RBV permanently discontinued treatment due to adverse
reactions. The frequency of serious adverse reactions and
discontinuations due to adverse reactions in subjects with
compensated cirrhosis were comparable to those seen in subjects
without cirrhosis.
When ZEPATIER was studied with RBV, the most frequent adverse
reactions to ZEPATIER + RBV combination therapy were consistent
with the known safety profile of RBV.
Very common (≥ 1/10) adverse reactions identified with ZEPATIER,
based on pooled data from patients treated for 12 weeks without
RBV, include headache and fatigue. Common (≥ 1/100 to < 1/10)
adverse reactions include decreased appetite, insomnia, anxiety,
depression, dizziness, nausea, diarrhea, constipation, upper
abdominal pain, abdominal pain, dry mouth, vomiting, pruritus,
alopecia, arthralgia, myalgia, asthenia, irritability.
Common adverse reactions of fatigue, headache, and nausea
occurred at a similar frequency in patients treated with ZEPATIER
or placebo.
For detailed information, please visit
http://ec.europa.eu/health/documents/community-register/2016/20160722135308/anx_135308_en.pdf.
MSD’s Commitment to HCV and Treatment Access
For more than 30 years, MSD has been at the forefront of the
response to chronic HCV infection, and we continue to work to
advance scientific understanding of this significant global public
health epidemic. MSD’s chronic HCV clinical development programs
have included more than 135 clinical trials in approximately 40
countries and have enrolled nearly 10,000 participants.
MSD believes scientific advancements must be supported by a
commitment to access to make a meaningful difference in the lives
of patients. While the latest innovations in chronic HCV treatment
that have become available over recent years provide Europe with an
unprecedented opportunity to significantly reduce the burden of
HCV, an urgent medical need remains. It is estimated that less than
one in five diagnosed chronic HCV patients are currently treated in
the largest countries within Europe (France, Germany, Italy, Spain
and United Kingdom), with thousands of new cases each year. As part
of our longstanding leadership in infectious disease and experience
in delivering market-defined access programs, MSD will continue to
collaborate with stakeholders to ensure ZEPATIER is an option for
all patients for whom it is indicated. Together, we believe we can
facilitate the collective goal of addressing the global burden of
chronic HCV.
About MSD
For 125 years, MSD has been a global health care leader working
to help the world be well. MSD is a tradename of Merck & Co.,
Inc., Kenilworth, N.J., USA. 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.
Forward-Looking Statement of Merck & Co., Inc.,
Kenilworth, N.J., USA
This news release of Merck & Co., Inc., Kenilworth, N.J.,
USA (the “company”) includes “forward-looking statements” within
the meaning of the safe harbor provisions of the U.S. Private
Securities Litigation Reform Act of 1995. These statements are
based upon the current beliefs and expectations of the company’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; the company’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 the company’s patents and other
protections for innovative products; and the exposure to
litigation, including patent litigation, and/or regulatory
actions.
The company 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 the company’s 2015
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).
# # #
Please see European Summary of Product Characteristics for
ZEPATIER (elbasvir/grazoprevir) at
http://ec.europa.eu/health/documents/community-register/2016/20160722135308/anx_135308_en.pdf.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20160729005054/en/
MerckMedia:Pamela Eisele, +1 267 305 3558orSarra Herzog, +1 201
669 6570orInvestors:Teri Loxam, +1 908 740 1986orAmy Klug, +1 908
740 1898
Merck (NYSE:MRK)
Historical Stock Chart
From Mar 2024 to Apr 2024
Merck (NYSE:MRK)
Historical Stock Chart
From Apr 2023 to Apr 2024