BARACLUDE(R) (entecavir) Approved by the European Commission for the Treatment of Chronic Hepatitis B in Adult Patients With Evidence of Decompensated Liver Disease
the European Commission on
(CHB) in adult patients with evidence of decompensated liver disease.
BARACLUDE(r) was already approved in
patients with CHB 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.
This approval grants BARACLUDE(r) marketing authorisation in the 27
countries of the European Union. In the U.S., the Food and Drug
Administration (FDA) approved the decompensated indication for BARACLUDE(r)
Decompensated liver disease is characterised by failure of the liver to
maintain adequate function, usually due to severe scarring, leading to
fibrosis and/or cirrhosis caused by chronic liver inflammation. It
represents the end stage of hepatitis. Natural history data demonstrate that
up to 40% of patients with CHB develop cirrhosis over their lifetimes, at a
reported rate of 2-6% per year. Among CHB patients with cirrhosis, 3-5%
per year progress to decompensated cirrhosis and 2-5% develop hepatocellular
carcinoma (HCC).[2,3] Currently, the median survival rate in decompensated
patients is two to three years, with only 28% of patients surviving for more
than five years.[1,4] Once liver disease progresses to the decompenstated
stage, a liver transplant is often necessary.
“The approval of this additional indication is an important milestone for
CHB patients living with decompensated liver disease, a difficult to treat
population whose mortality rates are high,” said Professor
“The data used to support this indication shows that BARACLUDE(r) is
efficacious in treating decompensated patients.”
This approval is based on a randomised, open-label, multi-centre study
(ETV-048) that compared the efficacy & safety of BARACLUDE(r) (1.0 mg once
daily) with adefovir (10.0 mg once daily) administered in patients with HBeAg
positive or negative CHB who had evidence of liver decompensation.
Data demonstrated that BARACLUDE(r) showed greater viral suppression
compared to adefovir at 24 and 48 weeks following treatment initiation. At 48
weeks, 57% (57/100) of patients treated with BARACLUDE(r) achieved an
undetectable viral load (less than or equal to 300 copies/ml) compared to 20%
(18/91) of patients on adefovir.
ETV-048 Study Results
The 048 study evaluated 191 patients who were either HBeAG-positive or
HBeAG-negative. Patients were either treatment-naive or had been previously
treated excluding pre-treatment with BARACLUDE(r), adefovir or tenofovir.
Patients were randomised to receive BARACLUDE(r) (1.0 mg once daily) or
adefovir (10.0 mg once daily) and were analysed through 48 weeks.
Baseline demographics were similar for both groups. Importantly, at
baseline, patients had a mean CPT (child-pugh score) of 8.81 in the
BARACLUDE(r) arm and 8.35 in the adefovir arm, and the mean MELD (Model for
End stage Liver Disease) score was 17.1 and 15.3, respectively. Both of these
parameters measure the severity of hepatic decompensation.
The mean age of the study population was 52 years and the majority of the
subjects were male (74%) and either Asian (54%) or Caucasian (33%).
In the primary efficacy endpoint of mean change from baseline in serum
HBV DNA at Week 24, BARACLUDE(r) was superior to adefovir (-4.48 versus
-3.40; p < 0.0001).
Secondary efficacy endpoints included mean change from baseline in serum
HBV DNA at Week 48 (-4.66 in the BARACLUDE(r) arm and -3.90 in the adefovir
arm). In addition a greater proportion of patients on BARACLUDE(r) achieved
an undetectable viral load compared to patients on adefovir at 48 weeks: 57%
(57/100) versus 20% (18/91), respectively. Also patients on the BARACLUDE(r)
arm decreased their MELD score from baseline by -2.6% versus -1.7% in the
adefovir arm at Week 48, even though baseline MELD score had been higher with
17.1 for BARACLUDE(r) than 15.3 for adefovir. Further the normalization of
ALT (Alanine Aminotransferase enzyme) was achieved to a higher proportion in
the BARACLUDE(r)-treated patients (less than or equal to 1 x Upper Limit of
Normal) at Week 48 [63% (49/78)] compared with adefovir-treated patients [46%
The time to onset of HCC or death was comparable in the two treatment
groups; on-study cumulative death rates were 23% (23/102) and 33% (29/89) for
patients treated with BARACLUDE(r) and adefovir, respectively; and on-study
cumulative rates of HCC were 12% (12/102) and 20% (18/89) for BARACLUDE(r)
and adefovir, respectively.
BARACLUDE(r) was generally well tolerated and safety results were
comparable between the treatment groups and consistent with those previously
reported for a population with decompensated liver disease. Serious adverse
events occurred in 69% of the BARACLUDE(r) patients and 66% of the
adefovirpatientsand discontinuations due to adverse events occurred in 7% of
the Baraclude patients and 6 % of the adefovir patients.
Important Information About BARACLUDE(r)
Discovered at Bristol-Myers Squibb, BARACLUDE(r) 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.
A higher rate of serious hepatic adverse events (regardless of causality)
has been observed in patients with decompensated liver disease, in particular
in those with Child-Turcotte-Pugh (CTP) class C disease, compared with rates
in patients with compensated liver function. In addition, patients with
decompensated liver disease may be at higher risk for lactic acidosis and
specific renal adverse events such as hepatorenal syndrome. Clinical and
laboratory parameters should be closely monitored in this patient population.
* For full prescribing information for BARACLUDE(r), please consult the
Summary of Product Characteristics.
About Chronic Hepatitis B (CHB)
Chronic hepatitis B is a serious global health issue. Worldwide, more
than 2 billion people have been in contact with the hepatitis B virus and
approximately 350 million people are chronically infected.
About Decompensated Liver Disease
Decompensated liver disease is characterised by failure of the liver to
maintain adequate function, often due to severe scarring leading to fibrosis
and/or cirrhosis caused by chronic liver inflammation. Symptoms of liver
decompensation can include but are not limited to: jaundice (yellowing of the
skin or eyes), ascites (swollen abdomen from abnormal accumulation of fluid),
oesophageal varices (distorted blood vessels that may cause potentially fatal
bleeding), and hepatic encephalopathy ( neuropsychiatric abnormality
resulting in personality changes, intellectual impairment and reduced levels
About Bristol-Myers Squibb
discovering, developing and delivering innovative medicines that help
patients prevail over serious diseases.
BARACLUDE(R) (entecavir) is a registered trademark of Bristol-Myers
1. D’Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic
indicators of survival in cirrhosis: a systematic review of 118 studies. J.
Hepatol. 2006; 44: 217-31.
2. Chu C-M and Liaw Y-F. Hepatitis B virus-related cirrhosis: Natural
history and treatment. Seminars in Liver Disease 2006;26(2):142-152.
3. Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular
carcinoma in cirrhosis: Incidence and risk factors. Gastroenterology
2004;127(5 Suppl 1):S35-S50.
4. Fattovich G, Pantalena M, Zagni I et al. Effect of hepatitis B and C
virus infections on the natural history of compensated cirrhosis: a cohort
study of 297 patients. Am. J. Gastroenterol. 2002; 97: 2886-95.
5. Y. Liaw, et al. Efficacy and Safety of Entecavir versus Adefovir in
Chronic Hepatitis B Patients with Evidence of Hepatic Decompensation.
Abstract and Poster 442. AASLD 2009.
6. World Helath Organization Web site. Fact sheet N- 204.
SOURCE Bristol-Myers Squibb