Bristol-Myers
Squibb Company (NYSE:BMY) today announced that the European
Commission has approved Daklinza (daclatasvir), a potent,
pan-genotypic NS5A replication complex inhibitor (in vitro), for
use in combination with other medicinal products across genotypes 1, 2,
3 and 4 for the treatment of chronic hepatitis C virus (HCV) infection
in adults. Daklinza, when used in combination with sofosbuvir, is
an all-oral, interferon-free regimen that provided cure rates of up to
100% in clinical trials, including patients with advanced liver disease,
genotype 3 and those who have previously failed treatment with protease
inhibitors. Daklinza is the first NS5A complex inhibitor approved
in the European Union (EU) and will be available for use in combination
with other medicinal products, providing a shorter treatment duration
(12 or 24 weeks) compared to 48 weeks of treatment with interferon- and
ribavirin-based regimens.
Today’s approval allows for the marketing of Daklinza in all 28
Member States of the EU. The marketing authorization for Daklinza
follows an accelerated assessment by the Committee for Medicinal
Products for Human Use (CHMP), a designation that is granted to new
medicines of major public health interest.
“HCV is a challenging virus to overcome, requiring multiple modes of
attack. With the approval of Daklinza, we have a new class of
drug that disrupts the virus in two ways - by inhibiting both viral
replication and assembly - and when combined with other compounds often
results in cure among even the hardest-to-treat patients,” said Michael
P. Manns, MD, Professor and Chairman, Department of Gastroenterology,
Hepatology, and Endocrinology, Hannover Medical School, Hannover,
Germany.
Of the estimated nine million people living with HCV in the EU, genotype
1 is the most common genotype, though distribution varies across the
region. The burden of liver disease and other morbidities from HCV
infection is significant in Europe, where HCV accounts for 63% of liver
transplants among patients with virus-related liver disease. Patient
populations with high unmet needs include those with advanced liver
disease, protease inhibitor failure, genotype 3, HIV co-infected
patients and those who have undergone liver transplant.
“The eradication of HCV is in sight, and with today’s approval, Daklinza,
in combination with other agents, will be an important option to achieve
cure across many HCV genotypes and patient types for those in the EU who
are in dire need of new treatment choices,” said Emmanuel Blin, Head of
Worldwide Commercialization, Bristol-Myers Squibb. “We are proud to have
discovered, developed and now brought to market this first-in-class NS5A
replication complex inhibitor. We look forward to our continued work
with EU health authorities to ensure Daklinza-based regimens are
available to patients as quickly as possible.”
The approval of Daklinza is supported by data from multiple
studies, including an open-label, randomized study of Daklinza with
sofosbuvir in genotypes 1, 2, and 3, including patients with no response
to prior therapy with telaprevir or boceprevir and patients with
fibrosis. Results showed that a regimen of Daklinza with
sofosbuvir achieved SVR12 (sustained virologic response 12
weeks after the end of treatment; a functional cure) in 99% of
treatment-naïve patients with HCV genotype 1, 100% of patients with
genotype 1 who had failed treatment with either telaprevir or
boceprevir, 96% of those with genotype 2 and 89% of those with genotype
3.
In addition, the regimen resulted in low rates of discontinuation (<1%)
due to adverse events (AEs). The rate of serious adverse
events (SAEs) was low (4.7%). The most common adverse events were
fatigue, headache and nausea. Across clinical studies, Daklinza-based
regimens have been generally well tolerated with low rates of
discontinuation across a range of patients. Ongoing and completed Daklinza
studies have included more than 5,500 patients in a variety of all-oral
regimens and with the current interferon-based standard of care.
The safety of Daklinza for the treatment of hepatitis C has been
demonstrated in diverse patient populations that include elderly
patients, patients with advanced liver disease, post-liver transplant
recipients and patients co-infected with HIV. No unique safety concerns
have been identified in patients who were treated with Daklinza
across clinical studies and in the early access program. Several of
these studies are ongoing.
Recommended regimens and treatment duration for Daklinza combination
therapy include:
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HCV genotype and patient population
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Treatment
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Duration
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Genotype 1 or 4 without cirrhosis
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Daklinza + sofosbuvir
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12 weeks
Consider prolongation of treatment to 24 weeks for patients with
prior treatment including a NS3/4A protease inhibitor (see
sections 4.4 and 5.1).
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Genotype 1 or 4 with compensated cirrhosis
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Daklinza + sofosbuvir
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24 weeks
Shortening treatment to 12 weeks may be considered for previously
untreated patients with cirrhosis and positive prognostic factors
such as IL28B CC genotype and/or low baseline viral load.
Consider adding ribavirin for patients with very advanced liver
disease or with other negative prognostic factors such as prior
treatment experience.
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Genotype 3 with compensated cirrhosis and/or treatment experienced
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Daklinza + sofosbuvir + ribavirin
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24 weeks
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Genotype 4
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Daklinza + peginterferon alfa + ribavirin
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24 weeks of Daklinza in combination with 24-48 weeks of
peginterferon alfa and ribavirin.
If the patient has HCV RNA undetectable at both treatment weeks 4
and 12, all 3 components of the regimen should be continued for a
total duration of 24 weeks. If the patient achieves HCV RNA
undetectable, but not at both treatment weeks 4 and 12, Daklinza
should be discontinued at 24 weeks and peginterferon alfa and
ribavirin continued for a total duration of 48 weeks.
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Daklinza monotherapy is not recommended. The Summary of Product
Characteristics will be available at www.ema.europa.eu.
Commercial availability of Daklinza in the EU will be determined
by individual Member States.
About Hepatitis C
Globally, there are 150 million people infected with HCV and of that, an
estimated 9 million people are living with hepatitis C in the European
Union (EU). Hepatitis C is a virus that infects the liver and is
transmitted through direct contact with infected blood and blood
products. Up to 90 percent of those infected with hepatitis C
will not spontaneously clear the virus and will become chronically
infected. According to the World Health Organization, 20 percent of
people with chronic hepatitis C will develop cirrhosis and, of those,
about 5 to 7 percent of patients may ultimately die of the consequences
of infection.
About Bristol-Myers Squibb’s HCV Portfolio
Bristol-Myers Squibb’s research efforts are focused on advancing
late-stage compounds to deliver the most value to patients with
hepatitis C. At the core of our pipeline is daclatasvir, a potent
pan-genotypic NS5A complex inhibitor (in vitro), which continues
to be investigated in multiple treatment regimens and in people with
co-morbidities.
Daklinza was recently approved in Japan in combination with Sunvepra
(asunaprevir), a NS3/4A protease inhibitor. The Daklinza+Sunvepra
Dual Regimen is Japan’s first all-oral, interferon- and ribavirin-free
treatment regimen for patients with genotype 1 chronic HCV infection,
including those with compensated cirrhosis.
Applications for the daclatasvir Dual Regimen are also under review by
the U.S. Food and Drug Administration (FDA), which granted priority
review status and set a target review date under the Prescription Drug
User Fee Act (PDUFA) of November 30, 2014.
In 2014, the FDA granted Bristol-Myers Squibb’s investigational
daclatasvir Dual Regimen (daclatasvir + asunaprevir) Breakthrough
Therapy Designation for use as a combination therapy in the treatment of
genotype 1b HCV infection.
In 2013, Bristol-Myers Squibb’s investigational all-oral 3DAA Regimen
(daclatasvir/asunaprevir/BMS-791325) also received Breakthrough Therapy
Designation in the U.S., which helped to expedite the start of the
ongoing Phase 3 UNITY Program. Study populations include non-cirrhotic
naïve, cirrhotic naïve and previously treated patients. The daclatasvir
3DAA Regimen is being studied as a fixed-dose-combination treatment with
twice daily dosing.
Additional studies with daclatasvir in combination with sofosbuvir are
being conducted in high unmet need patients, such as pre- and
post-transplant patients, HIV/HCV co-infected patients and patients with
genotype 3 as part of the ongoing Phase 3 ALLY Program.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission
is to discover, develop and deliver innovative medicines that help
patients prevail over serious diseases. For more information, please
visit http://www.bms.com or
follow us on Twitter at http://twitter.com/bmsnews.
Bristol-Myers Squibb Forward Looking Statement
This press release contains "forward-looking statements" as that term
is defined in the Private Securities Litigation Reform Act of 1995
regarding the research, development and commercialization of
pharmaceutical products. Such forward-looking statements are based on
current expectations and involve inherent risks and uncertainties,
including factors that could delay, divert or change any of them, and
could cause actual outcomes and results to differ materially from
current expectations. No forward-looking statement can be guaranteed.
Among other risks, there can be no guarantee that Daklinza will be a
commercially successful product. Forward-looking statements in this
press release should be evaluated together with the many uncertainties
that affect Bristol-Myers Squibb's business, particularly those
identified in the cautionary factors discussion in Bristol-Myers
Squibb's Annual Report on Form 10-K for the year ended December 31,
2013, in our Quarterly Reports on Form 10-Q and our Current Reports on
Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly
update any forward-looking statement, whether as a result of new
information, future events or otherwise.
Copyright Business Wire 2014