Daclatasvir+sofosbuvir+ribavirin regimen for
12 or 16 weeks achieved SVR12 rates of 88% and 92%, respectively,
in genotype 3 patients with advanced fibrosis or cirrhosis
Bristol-Myers Squibb Company (NYSE:BMY) today announced
late-breaking data from the Phase 3 ALLY-3+ trial investigating a
regimen of Daklinza (daclatasvir, DCV) in combination with
sofosbuvir (SOF) and ribavirin (RBV) in genotype 3 hepatitis C
(HCV) patients with advanced fibrosis or cirrhosis, for treatment
durations of 12 and 16 weeks. This patient population is one of the
most difficult to treat, among whom sustained virologic response
(SVR) rates, or cure, have proved harder to achieve.
The results show that 100% of patients in the advanced fibrosis
(F3) cohort achieved SVR12 in both the 12- and 16-week arms of the
study. SVR12 rates were 83% and 89% in patients with cirrhosis in
the 12- and 16-week arms, respectively. Results will be presented
today at The Liver Meeting® 2015, the annual meeting of The
American Association for the Study of Liver Diseases (AASLD), in
San Francisco, CA, November 13 – 17.
Daklinza is an NS5A replication complex inhibitor approved by
the U.S. Food and Drug Administration (FDA) for use with sofosbuvir
for the treatment of adults with HCV genotype 3. Sustained
virologic response (SVR) rates are reduced in HCV genotype
3-infected patients with cirrhosis receiving Daklinza in
combination with sofosbuvir for 12 weeks. Daklinza is
contraindicated in combination with medicinal products that
strongly induce CYP3A and P-glycoprotein transporter, as this may
lead to lower exposure and loss of efficacy
of Daklinza. Daklinza must not be administered as a
monotherapy.
“High cure rates for patients with genotype 3 with advanced
fibrosis or cirrhosis have remained elusive, so we are encouraged
by these results,” said Dr. Alex Thompson, Professor, St. Vincent's
Hospital and the University of Melbourne, Australia. “Our hope with
the ALLY-3+ trial was to study this investigational regimen in the
most difficult-to-cure genotype 3 patients, and to improve cure
rates for this patient population.”
In the ALLY-3+ study, the daclatasvir+sofosbuvir+ribavirin
combination regimen had no discontinuations due to adverse events
(AEs) or treatment-related serious AEs. The most frequent AEs were
insomnia (30%), fatigue (26%) and headache (24%). Additionally,
relapse occurred in four patients (two in the 16-week and two in
the 12-week arm). There was one death (12-week arm; not
treatment-related). There were no virologic breakthroughs.
“Our continued scientific exploration of the potential for
Daklinza used in combination with other direct-acting antivirals
for HCV patients has yielded these encouraging results,” said
Douglas Manion, M.D., head of Specialty Development, Bristol-Myers
Squibb. “We remain committed to delivering therapeutic options to
HCV patients with unmet needs around the globe, including those
with more complicated disease and other difficult-to-treat groups
such as genotype 3 patients with more advanced liver disease who
still need help to achieve cure.”
ALLY-3+ Study Design
This open-label, Phase 3b study in HCV genotype 3-infected
treatment-naive or -experienced patients with advanced fibrosis or
compensated cirrhosis randomized patients 1:1 to receive 12 weeks
versus 16 weeks of Daklinza (60 mg QD) + SOF (400 mg QD) + RBV
(weight-based), stratified by advanced fibrosis or cirrhosis
status.
Fifty patients were treated (12 weeks: 24 patients; 16 weeks: 26
patients). The majority of patients were male (80%), white (98%),
and treatment-experienced (74%; 10% prior relapse on SOF+RBV); 72%
had cirrhosis and 52% had HCV RNA ≥6 million IU/mL. Baseline
characteristics were comparable between arms.
The primary endpoint was to estimate SVR12 in treatment-naive or
-experienced subjects with compensated advanced fibrosis/cirrhosis
(F3-F4) treated for 12 weeks and for 16 weeks.
The full abstract for the presentation, containing the SVR4
data, is available at The Liver Meeting website.
About Genotype 3
Affecting an estimated 54.3 million people (30% of all HCV
patients) worldwide, genotype 3 is the second most common HCV
genotype globally and is considered one of the most difficult to
treat. The more aggressive nature of genotype 3 lies in the damage
it causes to the liver, as it is associated with accelerated
fibrosis progression. Recent research has also shown the risk of
cirrhosis for patients infected with HCV genotype 3 is 31% greater
than for those with HCV genotype 1.
About Bristol-Myers Squibb in HCV
Bristol-Myers Squibb is focused on helping to eradicate
hepatitis C around the world, with a primary emphasis on
difficult-to-treat patients, including those millions in countries
such as China where population-based HCV solutions remain a high
unmet need. Among the company’s data being presented at AASLD this
year is the first all-oral, DAA Phase 3 trial in HCV completed in
China.
In July 2014, Japan became the first country in the world to
approve the use of a daclatasvir-based regimen for the treatment of
chronic hepatitis C. Since then, daclatasvir-based regimens have
been approved in more than 50 countries across Europe, Central and
South America, the Middle East and the Asia-Pacific region.
Indication and Important Safety Information - DAKLINZA™
(daclatasvir)
INDICATION
DAKLINZA™ (daclatasvir) is indicated for use with sofosbuvir for
the treatment of adults with genotype 3 chronic hepatitis C virus
(HCV) infection.
Limitations of Use:
- Sustained virologic response (SVR)
rates are reduced in HCV genotype 3-infected patients with
cirrhosis receiving DAKLINZA in combination with sofosbuvir for 12
weeks.
IMPORTANT SAFETY INFORMATION
- Drugs Contraindicated with
DAKLINZA: strong inducers of CYP3A that may lead to loss of
efficacy of DAKLINZA include, but are not limited to:
- Phenytoin, carbamazepine, rifampin, St.
John’s wort (Hypericum perforatum)
WARNINGS and PRECAUTIONS
- Risk of Adverse Reactions or Loss of
Virologic Response Due to Drug Interactions: Coadministration
of DAKLINZA and other drugs may result in known or potentially
significant drug interactions. Interactions may include the loss of
therapeutic effect of DAKLINZA and possible development of
resistance, dosage adjustments for other agents or DAKLINZA,
possible clinically significant adverse events from greater
exposure for the other agents or DAKLINZA.
- Serious Symptomatic Bradycardia When
Coadministered with Sofosbuvir and Amiodarone: Post-marketing
cases of symptomatic bradycardia and cases requiring pacemaker
intervention have been reported when amiodarone is coadministered
with sofosbuvir in combination with another direct-acting
antiviral, including DAKLINZA. A fatal cardiac arrest was reported
with ledispasvir/sofosbuvir.
- Coadministration of amiodarone with
DAKLINZA in combination with sofosbuvir is not recommended. For
patients taking amiodarone who have no alternative treatment
options, patients should undergo cardiac monitoring, as outlined in
Section 5.2 of the prescribing information.
- Bradycardia generally resolved after
discontinuation of HCV treatment.
Adverse Reactions
- The most common adverse
reactions were (≥ 5%): headache (14%), fatigue (14%), and
nausea (8%), diarrhea (5%).
Drug Interactions
- CYP3A: DAKLINZA is a substrate.
Moderate or strong inducers may decrease plasma levels and effect
of DAKLINZA. Strong inhibitors (e.g., clarithromycin, itraconazole,
ketoconazole, ritonavir) may increase plasma levels of
DAKLINZA.
- P-gp, OATP 1B1 and 1B3, and
BCRP: DAKLINZA is an inhibitor, and may increase exposure to
substrates, potentially increasing or prolonging their adverse
effect.
See Section 7 of the Full Prescribing Information for
additional established and other potentially significant drug
interactions and related dose modification recommendations.
Daklinza in Pregnancy: No data with Daklinza in pregnant
women are available to inform a drug-associated risk. Animal
studies of Daklinza at exposure above the recommended human dose
have shown maternal and embryofetal toxicity. Consider the benefits
and risks of Daklinza when prescribing Daklinza to a pregnant
woman.
Nursing Mothers: Daklinza was excreted into the milk of
lactating rats; it is not known if Daklinza is excreted into human
milk. Consider the benefits and risks to the mother and infant when
breastfeeding.
Please click here for the DAKLINZA full prescribing
information
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 approved for the additional indication
mentioned above. 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,
2014 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.
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version on businesswire.com: http://www.businesswire.com/news/home/20151116005400/en/
Bristol-Myers Squibb CompanyMedia:Robert Perry,
609-419-5378cell:
407-492-4616rob.perry@bms.comInvestors:Ranya Dajani,
609-252-5330ranya.dajani@bms.comBill Szablewski,
609-252-5894william.szablewski@bms.com
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