BARACLUDE® (entecavir) Demonstrated Greater Antiviral Efficacy Compared to Adefovir in New Study of Chronic Hepatitis B Patients with Evidence of Decompensated Cirrhosis

Study Addresses Unmet Medical Need for Difficult-to-Treat Patient Population
BOSTON--(Business Wire)--
Bristol-Myers Squibb (NYSE: BMY) today announced 48-week data from an ongoing
study (ETV-048) of chronic hepatitis B patients with decompensated cirrhosis, in
which BARACLUDE demonstrated greater viral suppression compared to adefovir. The
new BARACLUDE data were presented today at the 60th Annual Meeting of the
American Association for the Study of Liver Diseases.

Decompensated cirrhosis is characterized by severe scarring of the liver caused
by chronic liver inflammation, including inflammation associated with chronic
hepatitis B infection. It is estimated that 15 to 25 percent of chronic
hepatitis B patients die from complications of liver disease.1Currently, the
median survival rate in decompensated patients is two to three years, with only
28 percent of patients surviving for more than five years.2,3 The treatment of
chronic hepatitis B patients with decompensated cirrhosis remains an area of
unmet medical need, and these patients often require liver transplant.

"This study represents an important first step in addressing an unmet medical
need, as this is one of the first comparative studies to evaluate the safety and
efficacy of antiviral therapy in this difficult-to-treat patient population,"
said Professor Hugo Cheinquer, ETV-048 study investigator and associate
professor of gastroenterology and hepatology, Universidade Federal Do Rio Grande
Do Sul, Porto Alegre, Brazil. "Chronic hepatitis B is a lifelong disease and
these data suggest that treatment with BARACLUDE may offer chronic hepatitis B
patients with decompensated cirrhosis a treatment option."

Study Results through Week 48

The primary study endpoint of ETV-048 was the mean change from baseline HBV DNA
at Week 24, analyzed by linear regression and adjusted for baseline HBV DNA and
lamivudine resistance status. The study successfully met its primary objective;
at Week 24, BARACLUDE achieved a greater reduction in viral load than adefovir:
-4.48 (0.200) versus -3.40 (0.251) log copies/mL, respectively (p < 0.0001).

A statistically significant difference was observed in the proportion of
patients achieving undetectable viral load [HBV DNA <300 copies/mL as measured
by polymerase chain reaction (PCR)] and ALT normalization. At 24 weeks, 49
percent (49/100) of patients treated with BARACLUDE® (entecavir) achieved an
undetectable viral load, compared with 16 percent (15/91) of patients who
received adefovir; at 48 weeks, 57 percent (57/100) of patients on BARACLUDE
achieved an undetectable viral load, compared with 20 percent (18/91) of
patients on adefovir (p< 0.0001). Also, among patients with baseline abnormal
ALT, a higher proportion of BARACLUDE-treated patients achieved ALT
normalization at Weeks 24 and 48 [59 percent (46/78) and 63 percent (49/78)
respectively, compared with 39 percent (28/71) and 46 percent (33/71) of
adefovir-treated patients].

Additionally, of the 100 patients treated with BARACLUDE, 66 percent had an
improvement or no worsening of the Child-Pugh Score (which assesses severity of
hepatic decompensation), with 32 percent of patients having achieved a ≥ 2-point
reduction in Child-Pugh score at Week 24; these rates were 61 percent and 35
percent, respectively, at Week 48. Findings at Weeks 24 and 48 were comparable
for patients receiving adefovir; 71 percent saw an improvement or no worsening
of the Child-Pugh Score and 24 percent achieved a ≥ 2-point reduction in
Child-Pugh score at Week 24; these rates were 67 percent and 27 percent,
respectively, at Week 48. Patients treated with BARACLUDE also experienced an
improvement of the Model for End-Stage Liver Disease (MELD) Score (another
scoring system that assesses severity of hepatic decompensation). The change
from baseline for patients treated with BARACLUDE was a decrease of 2.6 points
compared with 1.7 points for patients treated with adefovir at Week 48.

The overall safety profile was comparable across the two treatments. As might be
expected in this patient population, the overall incidence of adverse events was
high with 89 percent (91/102) for the BARACLUDE arm and 97 percent (86/89) for
the adefovir arm. Serious adverse events occurred in 69 percent (70/102) and 66
percent (59/89) of BARACLUDE- and adefovir-treated patients, respectively. Rates
for death and hepatocellular carcinoma (HCC) were comparable. Overall, 23
percent (23/102) of BARACLUDE-treated patients died compared with 33 (29/89)
percent of adefovir-treated patients. HCC occurred in 12 percent (12/102) of the
BARACLUDE® (entecavir) arm compared with 20 (18/89) percent of the adefovir arm.
Renal function was monitored for all patients. Increases in serum creatinine
levels of ≥0.5 mg/dL from baseline were observed in 17 percent (17/102) of
BARACLUDE-treated and 24 percent (21/89) of adefovir-treated patients.

About Study ETV-048

Study ETV-048 is a randomized, open-label, comparative Phase IIIb study of
BARACLUDE compared to adefovir in treatment-naïve and lamivudine-experienced
patients with chronic hepatitis B infection and decompensated cirrhosis
(Child-Pugh score ≥ 7). The 195 adult patients (191 treated) were HBeAg-positive
or HBeAg-negative, and nucleos(t)ide-naïve or lamivudine pre-treated.

Patients were randomized to receive BARACLUDE 1 mg or adefovir 10 mg daily and
were treated for a minimum of 96 weeks. Baseline patient populations were
comparable in the two treatment arms. Patients had a mean MELD score of 17 and
15, respectively, in the BARACLUDE and adefovir treatment groups. Approximately
one third of patients were previously exposed and resistant to lamivudine.

The primary study endpoint was the mean change from baseline HBV DNA at Week 24,
analyzed by linear regression and adjusted for baseline HBV DNA and lamivudine
resistance status.

Secondary study endpoints specific to measuring improvement in cirrhosis
included the MELD Score, an exam which scores patients on the severity of
chronic liver disease, and the Child-Pugh Score (greater than or equal to a
two-point decrease), which were evaluated at baseline, Week 24 and Week 48.

About Chronic Hepatitis B

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. 4

INDICATION and IMPORTANT SAFETY INFORMATION about BARACLUDE® (entecavir)
Tablets:

INDICATION:

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.

This indication is based on histologic, virologic, biochemical, and serologic
responses in nucleoside-naïve and lamivudine-resistant adult patients with
HBeAg-positive or HBeAg-negative chronic HBV infection with compensated liver
disease. Limited data are available in adult patients with HIV/HBV co-infection
who have received prior lamivudine therapy. BARACLUDE has not been evaluated in
patients with decompensated liver disease.

IMPORTANT SAFETY INFORMATION:

* Severe acute exacerbations of hepatitis B have been reported in patients who
have discontinued anti-hepatitis B therapy, including BARACLUDE. 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). 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 and severe hepatomegaly with steatosis, including fatal cases,
have been reported with the use of nucleoside analogues alone or in combination
with antiretrovirals.
* There are no adequate and well-controlled studies of BARACLUDE® (entecavir) 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. Risks and benefits should be considered when deciding
whether to discontinue breastfeeding 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 (CAPD).
* 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.
* Since entecavir is primarily eliminated by the kidneys, 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 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.
* The most common adverse events of moderate to severe intensity among patients
treated with BARACLUDE® (entecavir) in clinical trials included: headache (4%),
fatigue (3%), diarrhea (1%), and dyspepsia (1%).

The recommended dose of BARACLUDE is 0.5 mg once daily in nucleoside-naïve
adults, and 1 mg once daily in lamivudine-refractory adults. 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 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.

Please see Full Prescribing Information, including boxed WARNINGS. For more
information, please visit www.BARACLUDE.com.

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. For more information, please visit www.bms.com.

BARACLUDE® (entecavir) is a registered trademark of Bristol-Myers Squibb.

References

1. NHS Choices. Complications of hepatitis B. Available at
http://www.nhs.uk/Conditions/Hepatitis-B/Pages/Complications.aspx. Accessed 15
September 2009

2. 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. 7 Ginés P, Quintero E, Arroyo V et al. Compensated
cirrhosis: natural history and prognostic factors. Hepatology 1987; 7: 122-8.

3. 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.

4. World Health Organization Web site. Fact sheet N°204.
http://www.who.int/mediacentre/factsheets/fs204/en/. Accessed August 28, 2009.

Bristol-Myers Squibb
Media:
Cristi Barnett
Office: 609-252-6028
Mobile: 609-306-1750
cristi.barnett@bms.com
or
Investors:
John Elicker
Office: 609-252-4611
john.elicker@bms.com

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