- Oral presentation on BARACLUDE® (entecavir) reinforces continued clinical development commitment in hepatitis B
- Oral presentations on hepatitis C investigational compounds BMS-790052 and BMS-650032 demonstrate advancement of robust pipeline
- Breadth of data highlights Company’s commitment to pursuing research that aims to improve the management of liver disease
PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol-Myers Squibb Company (NYSE: BMY) announced today that 22 abstracts on the Company’s research in liver disease have been accepted for presentation at The Liver Meeting® 2011, the 62nd annual meeting of the American Association for the Study of Liver Diseases (AASLD), in San Francisco, November 4 - 8. Bristol-Myers Squibb is advancing a portfolio of compounds that has the potential to address unmet medical needs for patients with liver disease, including BARACLUDE® (entecavir) for chronic hepatitis B (CHB), and the investigational compounds BMS-790052, BMS-650032 and PEG-Interferon lambda (Lambda) for hepatitis C (HCV) and brivanib for hepatocellular carcinoma (HCC).
Key presentations include an oral presentation on BARACLUDE monotherapy vs. combination therapy for CHB and two oral presentations of Phase II data on the Company’s investigational HCV direct-acting antivirals (DAAs). These presentations will highlight:
- The first data from the BE-LOW study, a Phase IIIb comparative study of BARACLUDE plus tenofovir vs. BARACLUDE monotherapy in treatment-naïve adults with CHB
- The first results from a Phase IIb study of the NS5A replication complex inhibitor BMS-790052 plus peginterferon alfa and ribavirin (alfa/RBV) in treatment-naive HCV genotype 1 and 4 patients, evaluating virologic response through 12 weeks on treatment (eRVR)
- The first results of a Phase IIa study of the dual DAA regimen of BMS-790052 and the NS3 protease inhibitor BMS-650032 in HCV genotype 1b-infected patients who have not responded to prior alfa/RBV therapy (null responders), evaluating sustained virologic response 12 weeks post-treatment (SVR12)
“Bristol-Myers Squibb is at the forefront of innovation in researching the treatment of liver diseases. In hepatitis C, where there remain considerable unmet medical needs, our goal is to increase treatment options for patients by developing a portfolio of compounds with different mechanisms of action,” 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 Liver Meeting help to expand our understanding of the potential efficacy and safety profiles of these investigational compounds and support the recent initiation of a broad Phase III development program in HCV.”
The Company will also present new data that further describe the mechanistic and clinical profile of Lambda, and real-world data that add to the understanding of the prevalence of and current treatment patterns in HBV, HCV and HCC, including an oral presentation of data from the BRIDGE study in HCC. The BRIDGE study is designed to develop global understanding of HCC, including assessment of treatment by geography and etiology, and associated clinical outcomes.
The complete list of Bristol-Myers Squibb data presentations is below. Abstracts can be accessed on the AASLD website at http://aasld2011.abstractcentral.com/login.
|Hepatitis B: BARACLUDE Clinical Data|
|Entecavir (ETV) monotherapy for 96 weeks is comparable to combination therapy with ETV plus tenofovir (TDF) in nucleos(t)ide-naïve patients with chronic hepatitis B (CHB): the BE-LOW study||Presidential Plenary III
8:00 am PST
|Hepatitis B: Outcomes Research / Real-World Data|
|Real World Data on Long Term Treatment Initiation in patients with Chronic Hepatitis B: cohort observations in France, Germany, Poland, Romania and Turkey||Nov. 5|
|Cost-effectiveness of entecavir versus adefovir for the treatment of chronic hepatitis B in patients with decompensated cirrhosis||Nov. 5|
|Treatment Patterns, Health Care Use, and Costs associated with First-Line Treatment for Chronic Hepatitis B with Entecavir versus Tenofovir||Nov. 5|
|Treatment Patterns, Health Care Use, and Costs associated with First-Line Treatment for Chronic Hepatitis B with Oral Antivirals Recommended by Current Guidelines versus Oral Antivirals Not Recommended by Current Guidelines||Nov. 5|
|Hepatitis C: Direct-Acting Antiviral Data|
|Dual Oral Combination Therapy with the NS5A Inhibitor BMS-790052 and the NS3 Protease Inhibitor BMS-650032 Achieved 90% Sustained Virologic Response (SVR12) in HCV Genotype 1b-Infected Null Responders||Nov. 7
3:30 pm PST
|BMS-790052, A NS5A Replication Complex Inhibitor, Combined with Peginterferon Alfa-2a and Ribavirin in Treatment-Naive HCV-Genotype 1 or 4 Patients: Phase 2b AI444010 Study Interim Week 12 Results||Presidential Plenary III
9:00 am PST
|Poster #381||Evaluation of drug interaction potential of the HCV protease inhibitor BMS-650032 at 200mg twice daily (BID) in metabolic cocktail and P-glycoprotein (P-gp) probe studies in healthy volunteers||Nov. 5|
|Poster #LB-20||Combination Therapy of Treatment-Naïve and Nonresponder Patients with HCV Genotype 1 Infection with BMS-790052, an NS5A Replication Complex Inhibitor, in Combination with Peginterferon Alfa-2a and Ribavirin||Nov. 7|
|Poster #LB-22||BMS-790052, an NS5A Replication Complex Inhibitor, in Combination with Peginterferon Alpha-2b and Ribavirin in Japanese Treatment-Naïve and Nonresponder Patients with Chronic HCV Genotype 1 Infection||Nov. 7|
|Poster #1362||Single-Dose Pharmacokinetics of BMS-790052 in Subjects with Hepatic Impairment Compared With Healthy Subjects||Nov. 7|
|Poster #1340||BMS-790052 Has No Effect on the Pharmacokinetics of a Combined Oral Contraceptive Containing Ethinyl Estradiol and Norgestimate in Healthy Female Subjects||Nov. 7|
|Hepatitis C: PEG-Interferon Lambda Data|
|Poster #376||The Effect of Pegylated Interferon Lambda on the Expression of Interferon Stimulated Genes in Whole Blood in Chronic Hepatitis C Patients in a Phase 2a Study||Nov. 5|
|Poster #1058||Implementation of an HCV Model for Il-28B Genotype Treatment Duration Optimization and Cure Rate Maximization for Pegylated Interferon Lambda||Nov. 6|
|Poster #1343||Pegylated Interferon Lambda Ameliorates Ribavirin (RBV)-Induced Anemia in HCV Patients by Maintaining Compensatory Erythropoiesis: Analysis of EMERGE Phase 2b Results through Week 12||Nov. 7|
|Poster #1344||Safety and Efficacy of Pegylated Interferon Lambda (peg-lambda) Compared to Pegylated Interferon α-2a (peg-alfa) in HCV-Infected Patients (G1/2/3) With Compensated Cirrhosis: EMERGE Phase IIB Efficacy and Safety Results through Week 12||Nov. 7|
|Poster #1363||Less severe flu-like symptoms with PEG-Interferon Lambda in Phase IIb Study of treatment-naive chronic hepatitis C (CHC) patients||Nov. 7|
|Hepatitis C: Epidemiology / Real-World Data|
|Poster #412||Prevalence of HCV and Host IL28B Genotypes in China||Nov. 5|
|Poster #1045||Adverse Events in Patients With Chronic Hepatitis C Treated With PegIFN-alfa and Ribavirin in Real-World Setting||Nov. 6|
|Poster #1084||Virologic Response among Hepatitis C (HCV) Patients Treated in Clinical Practice||Nov. 6|
|Poster #1736||Single nucleotide polymorphisms near IL28B and IL28A genes are associated with spontaneous seroclearance of HCV RNA in untreated patients with HCV infection||Nov. 7|
|Hepatocellular Carcinoma: Outcomes Research|
|Observations of Hepatocellular Carcinoma (HCC) Management Patterns from the Multinational HCC BRIDGE Study: First Overall Analysis of the North American Cohort||Nov. 8
11:15 am PST
INDICATION and IMPORTANT SAFETY INFORMATION about BARACLUDE® (entecavir)
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 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 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.
- 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 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.
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 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.
- Safety and effectiveness of BARACLUDE in pediatric patients below the age of 16 years have not been established.
- Dosage adjustment of BARACLUDE is recommended for patients with a creatinine clearance <50 mL/min, including those on hemodialysis or continuous ambulatory peritoneal dialysis.
- The safety and efficacy of BARACLUDE in liver transplant recipients are unknown. 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 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.
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 Full Prescribing Information, including boxed WARNINGS, available at www.BARACLUDE.com.
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.
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