Paris
-- March 1, 2011 -- Bristol-Myers Squibb (NYSE:BMY) announced
today that Baraclude (entecavir) has been approved by the
European Commission on February 28th 2011 to treat chronic
hepatitis B (CHB) in adult patients with evidence of
decompensated liver disease.
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Entecavir
(Baraclude) Tablet
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Baraclude
was already approved in Europe in June 2006 for use in
adult 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 marketing authorization in the
27 countries of the European Union. In the U.S., the Food
and Drug Administration (FDA) approved the decompensated
indication for Baraclude in October 2010.
Decompensated
liver disease is characterized 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). Currently,
the median survival rate in decompensated patients is
two to three years, with only 28% of patients surviving
for more than five years. Once liver disease progresses
to the decompensated 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 Jorg Petersen. "The
data used to support this indication shows that Baraclude
is efficacious in treating decompensated patients."
This
approval is based on a randomized, open-label, multi-centre
study (ETV-048) that compared the efficacy and safety
of Baraclude (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 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 achieved an undetectable viral load (less
than or equal to 300 copies/mL) compared to 20% (18/91)
of patients on adefovir [Hepsera].
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, adefovir, or tenofovir
[Viread].
Patients
were randomized to receive Baraclude (1.0 mg once daily)
or adefovir (10.0 mg once daily) and were analyzed 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 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 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 arm
and -3.90 in the adefovir arm). In addition a greater
proportion of patients on Baraclude 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 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 than 15.3 for adefovir. Further
the normalization of ALT (alanine aminotransferase enzyme)
was achieved to a higher proportion in the Baraclude-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% (33/71)].
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 and adefovir, respectively; and on-study cumulative
rates of HCC were 12% (12/102) and 20% (18/89) for Baraclude
and adefovir, respectively.
Baraclude
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 patients and 66% of the adefovir patients
and discontinuations due to adverse events occurred in
7% of the Baraclude patients and 6 % of the adefovir patients.
Important
Information About Baraclude
Discovered
at Bristol-Myers Squibb, Baraclude is indicated for the
treatment of chronic hepatitis B virus (HBV) infection
in adults with:
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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. |
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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, 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.
