Food and Drug Administration Approves Baraclude (entecavir)
as a Treatment for Chronic Hepatitis B Patients with Evidence
of Decompensated Liver Disease
load reduction at 48 weeks in difficult-to-treat chronic hepatitis
B patient population
At 48 weeks, 57 percent (57/100) of patients treated with
Baraclude achieved an undetectable viral load compared to
20 percent (18/91) of patients who received adefovir
Princeton, N.J. -- October 18, 2010 -- Bristol-Myers Squibb
Company (NYSE:BMY) announced today that the U.S. Food and
Drug Administration (FDA) has approved the supplemental New
Drug Application (sNDA) of Baraclude for the treatment of
chronic hepatitis B (CHB) in adult patients with decompensated
liver disease. Baraclude is indicated for the treatment of
CHB 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.
This new approval is based on virologic, biochemical, serologic,
and safety data from a controlled, ongoing, open-label Phase
IIIb study (ETV-048). This study compares BARACLUDE (1 mg
once daily) to adefovir (10 mg once daily) in CHB patients
with decompensated liver disease. Data demonstrated that Baraclude
was effective in this patient population. Baraclude showed
greater viral suppression compared to adefovir at 48 weeks
following treatment initiation.
"This additional indication for Baraclude is important
news as it is now proven to be an effective treatment option
for physicians to help in managing chronic hepatitis B patients
with decompensated liver disease,: said Dr. Naoky Tsai, MD,
professor of medicine at the John A. Burns School of Medicine
at the University of Hawaii, Honolulu.
Decompensated liver disease refers to failure of the liver
to maintain adequate function, often due to severe scarring
of the liver. Chronic hepatitis B infection is commonly associated
with chronic liver inflammation and can lead to decompensated
A key study endpoint of ETV-048 was the proportion of subjects
with undetectable HBV DNA viral load (< 300 copies/mL).
A greater proportion of patients on Baraclude (entecavir)
achieved an undetectable viral load compared to patients on
adefovir at 48 weeks: 57 percent (57/100) versus 20 percent
In the Baraclude arm, the most common adverse reactions of
any severity, regardless of causality, occurring through Week
48 were peripheral edema (16 percent), ascites (15 percent),
pyrexia (14 percent), hepatic encephalopathy (10 percent),
and upper respiratory infection (10 percent).
Additional ETV-048 Study Outcomes
Among patients with baseline abnormal alanine aminotransferase
(ALT), a higher proportion of Baraclude-treated patients achieved
ALT normalization (< 1 x Upper Limit of Normal)
at Week 48 [63 percent (49/78)] compared with adefovir-treated
patients [46 percent (33/71)].
One secondary study endpoint was the improvement in Child-Turcotte-Pugh
(CTP) Score, which scores patients on the severity of chronic
liver disease. Within this study, 61 percent (61/100) of patients
on Baraclude and 67 percent (61/91) of patients on adefovir
had an improvement or no worsening of the CTP Score at Week
48 compared to their baseline values.
Additionally, at Week 48 hepatitis B surface antigen (HBsAg)
loss was observed in 5 percent (5/100) of Baraclude-treated
patients and in none of the adefovir-treated patients (0/91).
Study ETV-048 Design
Study ETV-048 is a randomized, open-label Phase IIIb study
of BARACLUDE compared to adefovir in HBeAg-positive or HBeAg-negative
patients with chronic hepatitis B infection and evidence of
hepatic decompensation (CTP score > 7 with no upper
limit). Subjects were either HBV-treatment naïve or
previously treated predominantly with lamivudine or interferon-alpha.
Patients were randomized to receive Baraclude 1 mg once daily
(n=100) or adefovir 10 mg once daily (n=91). At baseline,
subjects had a mean serum HBV DNA by PCR of 7.83 log10 copies/mL
and mean ALT level of 100 U/L; 54% of subjects were HBeAg-positive;
35% had genotypic evidence of lamivudine resistance. The baseline
mean CTP score was 8.6.
About Baraclude (entecavir)
Baraclude, a nucleoside analogue discovered at Bristol-Myers
Squibb, was first approved in March 2005 for use in adult
chronic hepatitis B patients with compensated liver disease.
The initial approval was based on histologic, virologic, biochemical,
and serologic responses in nucleoside-treatment-naïve
and lamivudine-resistant adult subjects with HBeAg-positive
or HBeAg-negative CHB infection and compensated liver disease.
About Chronic Hepatitis B
Chronic hepatitis B is a serious viral infection that causes
damage to the liver. An estimated 1.25 million Americans are
chronically infected with hepatitis B, and over half are of
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 www.bms.com
or follow us on Twitter at www.twitter.com/bmsnews.
Squibb Company. U.S. Food and Drug Administration Approves Baraclude
(entecavir) as a Treatment for Chronic Hepatitis B Patients
with Evidence of Decompensated Liver Disease. Press release.
October 18, 2010.
Y. Liaw, M. Gigi, et al. Efficacy and Safety of Entecavir Versus
Adefovir in Chronic Hepatitis B Patients with Evidence of Hepatic
Decompensation. 60th Annual Meeting of the American Association
for the Study of Liver Diseases. Presented October 30 -- November
3, 2009. Poster Number 422.
Hepatitis B Foundation Website. Glossary. www.hepb.org/hepb/glossary.htm.
Accessed September 15, 2010.
Asian Liver Center Website. FAQ about Hepatitis B. www.liver.stanford.edu/Education/faq.html.
Accessed September 7, 2010.