Bristol-Myers Squibb to Present New Data on Hepatitis C and Hepatitis B Compounds at The International Liver CongressTM (ILC) 2013

Mon Apr 8, 2013 4:50am EDT

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* New data on an investigational, all-oral, triple DAA regimen of daclatasvir,
asunaprevir and BMS-791325 to be included in official ILC Press Conference on
April 24
* New ALT flare data further characterize profile of peginterferon lambda-1a
(Lambda) as investigational treatment for Chronic Hepatitis B (CHB)
* Breadth of data underscores Company`s commitment to advancing the treatment of
liver disease

PRINCETON, N.J.--(Business Wire)--
Bristol-Myers Squibb Company (NYSE:BMY) announced today that 14 abstracts on the
Company`s research in liver disease have been accepted for presentation at The
International Liver CongressTM 2013, the 48th annual meeting of the European
Association for the Study of the Liver (EASL), in Amsterdam, April 24 - 28. 

Key presentations include:

* New Phase 2 data on an investigational triple direct-acting antiviral (DAA)
regimen of daclatasvir (NS5A replication complex inhibitor), asunaprevir (NS3
protease inhibitor) and BMS-791325 (NS5B non-nucleotide polymerase inhibitor) in
patients with hepatitis C (HCV) genotypes 1a and 1b. The regimen is being
studied as a potential interferon alfa-, ribavirin- and ritonavir-free treatment
option to avoid the tolerability and drug-drug interaction profiles of these
medicines. These triple DAA data will be highlighted in the official ILC Press
Conference on April 24. 
* An analysis of all available safety data on 1,100 patients who received
daclatasvir plus interferon alfa and ribavirin in Phase 2 studies. These data
support the ongoing Phase 3 development program for daclatasvir and further
studies of daclatasvir as a component of DAA-based HCV treatment regimens. 
* A characterization of ALT flares observed in hepatitis B (HBV) treatment with
the investigational interferon Lambda vs. alfa interferon, reflecting differing
profiles for the two compounds. Lambda is being developed as a potential
alternative for alfa wherever interferon is used in the treatment of either HCV
or HBV. 
* An analysis of sustained virologic response with daclatasvir plus sofosbuvir,
with or without ribavirin, in patients with HCV genotype 1 who previously failed
telaprevir or boceprevir.

"Bristol-Myers Squibb has a longstanding commitment to viral hepatitis and has
been at the forefront of the evolving science in both hepatitis B and C," said
Brian Daniels, MD, senior vice president, Global Development and Medical
Affairs, Research and Development, Bristol-Myers Squibb. "The data we are
presenting at the International Liver Congress demonstrate our continued
advancement of research to address unmet medical needs, through the development
of regimens for personalized hepatitis C treatment and increasing options to
treat hepatitis B."

Bristol-Myers Squibb is studying a portfolio of compounds that has the potential
to address unmet medical needs for patients with liver disease, including the
investigational compounds daclatasvir, asunaprevir and BMS-791325 for HCV, and
Lambda for HCV and HBV. In addition to these compounds, the Company`s medicine
BARACLUDE® (entecavir) is approved for the treatment of chronic hepatitis B
(CHB) in adults with evidence of active viral replication and either evidence of
persistent elevations in aminotransferases (ALT or AST), or histologically
active disease. 

The complete list of Bristol-Myers Squibb data presentations is below. Abstracts
can be accessed on the ILC/EASL website at
http://www.easl.eu/_the-international-liver-congress/general-information.

 Title                                                                                                                                                                                                               Date/Time           
 Hepatitis C: Direct-Acting Antiviral Data                                                                                                                                                                                               
                                                                                                                                                                                                                                         
 Synergistic Interactions of HCV NS5A replication Complex Inhibitors Sensitize Resistant Variants and Enhance the Efficacy of Daclatasvir (DCV, BMS-790052) In Vitro and In Vivo                                     April 25            
                                                                                                                                                                                                                     12:15 - 1:30 pm     
 Asunaprevir with Peginterferon and Ribavirin in Treatment-Naïve Patients with Genotype -1 or -4 Chronic Hepatitis C: SVR24 Results From a Randomized Phase 2b Study (AI447016)                                      April 25            
                                                                                                                                                                                                                     12:15 - 1:30 pm     
 Evaluation of Pharmacokinetic Drug-Drug Interaction (DDI) Between BMS-791325, an NS5B Non-Nucleotide Polymerase Inhibitor, Daclatasvir and Asunaprevir in Triple Combination in HCV Genotype 1-Infected Patients    April 25            
                                                                                                                                                                                                                     12:15 - 1:30 pm     
 The Effect of Coadministration of the Proton-Pump Inhibitor Omeprazole on the Pharmacokinetics of Daclatasvir in Healthy Subjects                                                                                   April 26            
                                                                                                                                                                                                                     12:30 - 2:00 pm     
 Exposure-Response Analyses of Asunaprevir in Combination with Daclatasvir ± Peginterferon / Ribavirin Among Patients with Genotype 1 Chronic HCV Infection: Dose Selection for Phase 3 Clinical Trials              April 26            
 -Response Analyses of Asunaprevir in Patients with Genotype 1, Chronic HCV Infection: Dose Selection for Phase 3 Clinical Trials                                                                                    12:30 - 2:00 pm     
 Daclatasvir Combined With Peginterferon Alfa and Ribavirin for 12 or 16 Weeks in Patients With HCV Genotype 2 or 3 Infection: COMMAND GT2/3 Study                                                                   April 27            
                                                                                                                                                                                                                     3:30 - 5:30 pm      
                                                                                                                                                                                                                     
Oral presentation  
 Sustained Virologic Response with Daclatasvir Plus Sofosbuvir ± Ribavirin (RBV) In Chronic HCV Genotype (GT) 1-Infected Patients who Previously Failed Telaprevir (TVR) or Boceprevir (BOC)                         April 27            
                                                                                                                                                                                                                     3:30 - 5:30 pm      
                                                                                                                                                                                                                     
Oral presentation  
 Safety Profile of Daclatasvir in Combination with Peginterferon Alfa and Ribavirin in 1100 Patients with Chronic HCV Infection Treated in Phase 2 Studies                                                           April 27            
                                                                                                                                                                                                                     12:30 - 1:30 pm     
 Pre-Existence, Emergence and Persistence of HCV Genotype 4 NS5A Resistance Variants from the Phase 2b COMMAND-1 Study: Daclatasvir Plus Peginterferon-Alfa/Ribavirin in Treatment-Naïve Patients                    April 27            
                                                                                                                                                                                                                     12:30 - 1:30 pm     
 Hepatitis C: Outcomes Research Data                                                                                                                                                                                                     
 Host Genetic Variants Around IL28A/IL28B Associated with HCV-Related Outcomes Based on R.E.V.E.A.L.-HCV Cohort                                                                                                      April 25            
                                                                                                                                                                                                                     12:15 - 1:30 pm     
 Genome-Wide Association Study to Identify Potential Single Nucleotide Polymorphisms Associated with Spontaneous Hepatitis C Virus Clearance Among Chronic Hepatitis C Patients                                      April 25            
                                                                                                                                                                                                                     12:15 - 1:30 pm     
 Hepatitis B: Peginterferon Lambda-1a Data                                                                                                                                                                                               
 ALT Flares During Treatment With Peginterferon Lambda or Peginterferon Alfa in Patients with HBeAg-Positive Chronic Hepatitis B Infection (CHB)                                                                     April 26            
                                                                                                                                                                                                                     12:30 - 2:00 pm     
 Hepatitis B: BARACLUDE® (entecavir) Data                                                                                                                                                                                                
 Impact of Entecavir Versus Lamivudine on Hepatic Covalently Closed-Circular DNA and Total Hepatic HBV DNA in Nucleoside-Naïve HBeAg Positive Chronic Hepatitis B Patients                                           April 26            
                                                                                                                                                                                                                     12:30 - 2:00 pm     
                                                                                                                                                                                                                                         


INDICATION and IMPORTANT SAFETY INFORMATION aboutBARACLUDE® (entecavir) Tablets:

INDICATION

BARACLUDE is indicated for the treatment of chronic hepatitis B virus (HBV)
infection in adults with evidence of active viral replication and either
evidence of persistent elevations in serum aminotransferases (ALT or AST) or
histologically active disease. 

The following points should be considered when initiating BARACLUDE:

* This indication is based on histologic, virologic, biochemical, and serologic
responses in nucleoside-treatment-naïve and lamivudine-resistant adult subjects
with HBeAg-positive or HBeAg-negative chronic HBV infection and compensated
liver disease. 
* Virologic, biochemical, serologic, and safety data are available from a
controlled study in adult subjects with chronic HBV infection and decompensated
liver disease. 
* Virologic, biochemical, serologic, and safety data are available for a limited
number of adult subjects with HIV/HBV co-infection who have received prior
lamivudine therapy.

IMPORTANT SAFETY INFORMATION

WARNINGS: SEVERE ACUTE EXACERBATIONS OF HEPATITIS B, PATIENTS CO-INFECTED WITH
HIV AND HBV, and LACTIC ACIDOSIS AND HEPATOMEGALY

* Severe acute exacerbations of hepatitis B have been reported in patients who
have discontinued anti-hepatitis B therapy, including entecavir. Hepatic
function should be monitored closely with both clinical and laboratory follow-up
for at least several months in patients who discontinue anti-hepatitis B
therapy. If appropriate, initiation of anti-hepatitis B therapy may be
warranted.
* Limited clinical experience suggests there is a potential for the development
of resistance to HIV (human immunodeficiency virus) nucleoside reverse
transcriptase inhibitors if BARACLUDE (entecavir) is used to treat chronic HBV
infection in patients with HIV infection that is not being treated. Therapy with
BARACLUDE is not recommended for HIV/HBV co-infected patients who are not also
receiving highly active antiretroviral therapy (HAART).
* Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases,
have been reported with the use of nucleoside analogues, alone or in combination
with antiretrovirals.

Warnings and Precautions

* Before initiating BARACLUDE® (entecavir) therapy, HIV antibody testing should
be offered to all patients. BARACLUDE has not been studied as a treatment for
HIV infection and is not recommended for this use. 
* Lactic acidosis with BARACLUDE use has been reported, often in association
with hepatic decompensation, other serious medical conditions, or drug
exposures. Patients with decompensated liver disease may be at higher risk for
lactic acidosis. BARACLUDE should be suspended in any patient who develops
clinical or laboratory findings suggestive of lactic acidosis or pronounced
hepatotoxicity.

Adverse Reactions

* In clinical trials in patients with compensated liver disease, the most common
(≥3%) adverse reactions of any severity with at least a possible relation to
study drug for BARACLUDE-treated subjects were headache, fatigue, dizziness, and
nausea. In these trials, the most common adverse reactions of moderate to severe
intensity (grades 2-4) were diarrhea, dyspepsia, nausea, vomiting, fatigue,
headache, dizziness, somnolence, and insomnia. 
* In the decompensated liver disease trial, the most common adverse reactions of
any severity among patients treated with BARACLUDE, regardless of causality,
included: peripheral edema (16%), ascites (15%), pyrexia (14%), hepatic
encephalopathy (10%), and upper respiratory infection (10%). In this trial, 18%
(18/102) of BARACLUDE (entecavir) patients and 20% (18/89) of adefovir patients
died during the first 48 weeks of therapy. The majority of those deaths were due
to liver related causes.

Drug Interactions

BARACLUDE is primarily eliminated by the kidneys, therefore coadministration of
BARACLUDE with drugs that reduce renal function or compete for active tubular
secretion may increase serum concentrations of either entecavir or the
coadministered drug. Patients should be monitored closely when receiving
BARACLUDE® (entecavir) with other renally-eliminated drugs. 

Pregnancy and Nursing Mothers

* There are no adequate and well-controlled studies of BARACLUDE in pregnant
women. BARACLUDE should be used during pregnancy only if clearly needed and
after careful consideration of the risks and benefits. 
* There are no studies on the effect of BARACLUDE on transmission of HBV from
mother to infant. Therefore, appropriate interventions should be used to prevent
neonatal acquisition of HBV. 
* It is not known whether BARACLUDE is excreted into human milk; however, many
drugs are excreted into breast milk. Due to the potential for serious adverse
reactions in nursing infants from BARACLUDE, risks and benefits should be
considered when deciding whether to discontinue breast-feeding or discontinue
BARACLUDE in nursing women.

Pediatric Use

* Safety and effectiveness of BARACLUDE in pediatric patients below the age of
16 years have not been established.

Renal Impairment

* Dosage adjustment of BARACLUDE is recommended for patients with a creatinine
clearance <50 mL/min, including those on hemodialysis or continuous ambulatory
peritoneal dialysis.

Liver Transplant Recipients

* Renal function must be carefully monitored both before and during treatment
with BARACLUDE in a liver transplant recipient who has received or is receiving
an immunosuppressant that may affect renal function, such as cyclosporine or
tacrolimus.

Dosage and Administration

BARACLUDE® (entecavir) should be administered on an empty stomach (at least 2
hours after a meal and at least 2 hours before the next meal). 

The recommended dose of BARACLUDE:

* in nucleoside-naïve adults and adolescents (16+ yrs) with compensated liver
disease is 0.5 mg once daily 
* in adults and adolescents (16+ yrs) with compensated liver disease, and
refractory to lamivudine or with known lamivudine or telbivudine resistance
mutations (rtM204I/V with or without rtL180M, rtL80I/V, or rtV173L) is 1 mg once
daily 
* in adults with decompensated liver disease is 1 mg once daily

The optimal duration of treatment with BARACLUDE for patients with chronic HBV
infection and the relationship between treatment and long-term outcomes such as
cirrhosis and hepatocellular carcinoma are unknown. 

Additional Information

BARACLUDE is not a cure for HBV. Patients should be advised that treatment with
BARACLUDE has not been shown to reduce the risk of transmission of HBV to others
through sexual contact or blood contamination. 

Please see accompanying Full Prescribing Information, including Boxed WARNINGS,
or click here. 

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 product
development. 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 the clinical
trials of these compounds will support regulatory filings, or that the compounds
will receive regulatory approvals or, if approved, that they will become
commercially successful products. 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, 2012, 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.

BARACLUDE® (entecavir) is a registered trademark of Bristol-Myers Squibb.

Media:
Sonia Choi, 609-252-5132
sonia.choi@bms.com
or
Carrie Fernandez, 609-252-4831
carrie.fernandez@bms.com
or
Investors:
John Elicker, 609-252-4611
john.elicker@bms.com
or
Ranya Dajani, 609-252-5330
ranya.dajani@bms.com
or
Ryan Asay, 609-252-5020
ryan.asay@bms.com

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