San Francisco, CA (PRWEB) November 09, 2011
Bristol-Myers Squibb Company (NYSE: BMY) today announced 96-week results from the BE‐LOW™ study, a Phase IIIb clinical trial comparing BARACLUDE monotherapy (0.5mg once daily) with BARACLUDE (0.5mg once daily) plus tenofovir (300mg once daily) in treatment-naïve adult patients with HBeAg-positive and HBeAg-negative chronic hepatitis B (CHB) with compensated liver disease. In this study, no statistically significant difference was observed between the two treatment arms in the primary efficacy endpoint of HBV DNA <50 IU/mL (approximately 300 copies per mL) (1) at 96 weeks: 76.4% in the BARACLUDE monotherapy arm and 83.2% in the BARACLUDE plus tenofovir arm (p=0.0882). Overall, both study arms had similar safety profiles. Serious adverse events (SAEs) in this study were reported in 6.6% (12/182) of patients in the BARACLUDE monotherapy arm and in 7.1% (14/197) of patients in the BARACLUDE plus tenofovir arm. These data were reported at the 62nd annual meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco, California (Abstract #223, presented orally during the Presidential Plenary Session on Viral Hepatitis).
“In these 96-week data comparing entecavir monotherapy to combination of entecavir plus tenofovir, we found that combination therapy did not result in statistically significant difference in virologic response compared to entecavir monotherapy. The BE-LOW study data confirmed the results of previous studies showing limited or no benefit of combination therapy compared to monotherapy for treatment-naïve patients with chronic hepatitis B,” said principal investigator Anna Lok, MD, FRCP, director of clinical hepatology and professor in the department of internal medicine at the University of Michigan Medical School in Ann Arbor.
In this study, 379 nucleos(t)ide-naïve patients with CHB were randomized to receive either BARACLUDE (entecavir) 0.5 mg once daily (n=182) or BARACLUDE 0.5 mg plus tenofovir 300 mg once daily (n=197). Key findings at week 96 are:
- A comparable proportion of patients in both treatment arms achieved the primary efficacy endpoint of HBV DNA <50 IU/mL at 96 weeks: 76.4% (139/182) in the BARACLUDE monotherapy arm and 83.2% (164/197) in the BARACLUDE plus tenofovir arm (p=0.0882).
- Among HBeAg-positive patients, the proportion achieving HBV DNA <50 IU/mL was 69.8% (88/126) in the BARACLUDE monotherapy arm versus 80.4% (111/138) in the BARACLUDE plus tenofovir arm (p=0.0460). Further analysis suggested that this difference could be accounted for by the subset of patients with a high baseline viral load. Among those HBeAg-positive patients with a baseline viral load <10^8 IU/mL, 83% achieved HBV DNA less than 50 IU/mL in both treatment arms (BARACLUDE monotherapy 39/47; BARACLUDE plus tenofovir 44/53; p=ns). However, for those with a baseline viral load ≥108 IU/mL, 62% (49/79) of the patients in the BARACLUDE monotherapy arm and 78.8% (67/85) of the patients in the BARACLUDE plus tenofovir arm achieved HBV DNA <50 IU/mL.
- Among HBeAg-negative patients, the proportion achieving HBV DNA <50 IU/mL was 91.1% (51/56) in the BARACLUDE monotherapy arm versus 89.8% (53/59) in the BARACLUDE plus tenofovir arm.
Secondary efficacy endpoints measured in the study included alanine aminotransferase (ALT) normalization, HBeAg seroconversion, and HBeAg loss. ALT normalization was observed in 81.9% (149/182) of patients in this study in the BARACLUDE (entecavir) monotherapy arm versus 69% (136/197) in the BARACLUDE plus tenofovir arm. HBeAg seroconversion was observed in 32.5% (41/126) of patients in the BARACLUDE (entecavir) monotherapy arm versus 21.7% (30/138) in the BARACLUDE plus tenofovir arm in this study.
Two patients (1.1%) in the BARACLUDE monotherapy arm compared to five patients (2.5%) in the BARACLUDE plus tenofovir arm discontinued treatment prior to week 96. Patients who discontinued therapy prior to week 96 were considered treatment failures.
The overall adverse event profiles were similar across study arms. A total of three deaths occurred among treated patients, all on the BARACLUDE plus tenofovir arm: one due to bile duct tumor; one due to a late-onset exacerbation of hepatitis which was associated with breakthrough viremia while on continued treatment; and one due to cardiac arrest. One patient (0.5%) in the BARACLUDE monotherapy arm and two patients (1.0%) in the BARACLUDE plus tenofovir arm experienced on treatment ALT flares, defined as greater than 2 x baseline ALT and greater than 10 x ULN. No patients (0.0%) in either arm experienced off-treatment ALT flares. Six patients (3.3%) in the BARACLUDE monotherapy arm and four (2.0%) patients in the BARACLUDE plus tenofovir arm experienced serum creatinine increase ≥0.3 mg/dL. A total of five malignancies occurred among patients in the study: four (2.2%) patients in the BARACLUDE monotherapy arm and one (0.5%) patient in the BARACLUDE plus tenofovir arm. In the BARACLUDE monotherapy arm, there were three diagnoses of hepatocellular carcinoma (two on-treatment and one off-treatment) and one case of gastric cancer. In the BARACLUDE plus tenofovir arm there was one case of breast cancer.
Two patients (1.0%) in the BARACLUDE monotherapy arm and seven patients (3.6%) in the BARACLUDE plus tenofovir arm experienced virologic breakthrough. No recognized genotypic resistance mutations were observed in either treatment arm.
About The Study
The BE-LOW study is an open-label, multicenter, Phase IIIb study of 379 nucleos(t)ide-naïve patients with CHB. The patients were randomized 1:1 and treated with either BARACLUDE 0.5 mg once daily (n=182) or BARACLUDE 0.5 mg plus tenofovir 300 mg once daily (n=197). Nucleos(t)ide-naïve, HBeAg-negative CHB patient enrollment was capped at 30%. The primary efficacy endpoint was the proportion of patients with HBV DNA <50 IU/mL at week 96.
About Chronic Hepatitis B
Approximately 350 million people worldwide are chronically infected with hepatitis B (approximately 5% of the world’s population) and 75% of these cases occur in the Asia-Pacific region.(2) Most people with chronic hepatitis B show no signs or symptoms, so many of those chronically infected are unaware of their status. A blood test can diagnose chronic hepatitis B. Patients should speak with their doctor about options available for this condition.
Discovered at Bristol-Myers Squibb, BARACLUDE® is indicated for the treatment of chronic hepatitis B virus (HBV) infection in adults with:
- compensated liver disease and evidence of active viral replication, persistently elevated serum alanine aminotransferase (ALT) levels and histological evidence of active inflammation and/or fibrosis
- decompensated liver disease
- For full prescribing information for BARACLUDE®, please consult the Summary of Product Characteristics.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company committed to discovering, developing and delivering innovative medicines that help patients prevail over serious diseases.
BARACLUDE® (entecavir) is a registered trademark of Bristol-Myers Squibb Company.
Media: Annie Simond, +33 1 58 83 65 66, annie.simond(at)bms(dot)com
(1) HBV DNA carries the genetic blueprint of the hepatitis B virus. The number of HBV DNA “copies” found in a person’s blood, or “viral load,” indicates how rapidly the virus is reproducing in their liver. Low levels of HBV DNA, recognized as 300 copies per milliliter or less, indicate an “inactive” hepatitis B infection.
(2) Hou J, Liu Z, Gu F. Epidemiology and Prevention of Hepatitis B Virus Infection. Int J Med Sci 2005; 2:50 - 57. Available from http://www.medsci.org/v02p0050.htm Accessed November 2011