2011-03-01

BARACLUDE(R) (entecavir) Approved by the European Commission for the Treatment of Chronic Hepatitis B in Adult Patients With Evidence of Decompensated Liver Disease


Paris (ots/PRNewswire) - Bristol-Myers Squibb announcedtoday that BARACLUDE(R) (entecavir) has been approved by the EuropeanCommission on February 28th 2011 to treat chronic hepatitis B (CHB)in adult patients with evidence of decompensated liver disease.

BARACLUDE(r) was already approved in Europe in June 2006 for usein adult patients with CHB with compensated liver disease andevidence of active viral replication, persistently elevated serumalanine aminotransferase (ALT) levels and histological evidence ofactive inflammation and/or fibrosis.

This approval grants BARACLUDE(r) marketing authorisation in the27 countries of the European Union. In the U.S., the Food and DrugAdministration (FDA) approved the decompensated indication forBARACLUDE(r) in October 2010.

Decompensated liver disease is characterised by failure of theliver to maintain adequate function, usually due to severe scarring,leading to fibrosis and/or cirrhosis caused by chronic liverinflammation.[1] It represents the end stage of hepatitis. Naturalhistory data demonstrate that up to 40% of patients with CHB developcirrhosis over their lifetimes, at a reported rate of 2-6% peryear.[1] Among CHB patients with cirrhosis, 3-5% per year progress todecompensated cirrhosis and 2-5% develop hepatocellular carcinoma(HCC).[2,3] Currently, the median survival rate in decompensatedpatients is two to three years, with only 28% of patients survivingfor more than five years.[1,4] Once liver disease progresses to thedecompenstated stage, a liver transplant is often necessary.

"The approval of this additional indication is an importantmilestone for CHB patients living with decompensated liver disease, adifficult to treat population whose mortality rates are high," saidProfessor Jorg Petersen. "The data used to support this indicationshows that BARACLUDE(r) is efficacious in treating decompensatedpatients."

This approval is based on a randomised, open-label, multi-centrestudy (ETV-048) that compared the efficacy & safety of BARACLUDE(r)(1.0 mg once daily) with adefovir (10.0 mg once daily) administeredin patients with HBeAg positive or negative CHB who had evidence ofliver decompensation.

Data demonstrated that BARACLUDE(r) showed greater viralsuppression compared to adefovir at 24 and 48 weeks followingtreatment initiation. At 48 weeks, 57% (57/100) of patients treatedwith BARACLUDE(r) achieved an undetectable viral load (less than orequal to 300 copies/ml) compared to 20% (18/91) of patients onadefovir.

ETV-048 Study Results

The 048 study evaluated 191 patients who were eitherHBeAG-positive or HBeAG-negative. Patients were eithertreatment-naive or had been previously treated excludingpre-treatment with BARACLUDE(r), adefovir or tenofovir.

Patients were randomised to receive BARACLUDE(r) (1.0 mg oncedaily) or adefovir (10.0 mg once daily) and were analysed through 48weeks.

Baseline demographics were similar for both groups. Importantly,at baseline, patients had a mean CPT (child-pugh score) of 8.81 inthe 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 ofhepatic decompensation.

The mean age of the study population was 52 years and themajority of the subjects were male (74%) and either Asian (54%) orCaucasian (33%).[5]

In the primary efficacy endpoint of mean change from baseline inserum 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 baselinein serum HBV DNA at Week 48 (-4.66 in the BARACLUDE(r) arm and -3.90in the adefovir arm). In addition a greater proportion of patients onBARACLUDE(r) achieved an undetectable viral load compared to patientson adefovir at 48 weeks: 57% (57/100) versus 20% (18/91),respectively. Also patients on the BARACLUDE(r) arm decreased theirMELD score from baseline by -2.6% versus -1.7% in the adefovir arm atWeek 48, even though baseline MELD score had been higher with 17.1for BARACLUDE(r) than 15.3 for adefovir. Further the normalization ofALT (Alanine Aminotransferase enzyme) was achieved to a higherproportion in the BARACLUDE(r)-treated patients (less than or equalto 1 x Upper Limit of Normal) at Week 48 [63% (49/78)] compared withadefovir-treated patients [46% (33/71)].

The time to onset of HCC or death was comparable in the twotreatment 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 werecomparable between the treatment groups and consistent with thosepreviously reported for a population with decompensated liverdisease. Serious adverse events occurred in 69% of the BARACLUDE(r)patients and 66% of the adefovirpatientsand discontinuations due toadverse events occurred in 7% of the Baraclude patients and 6 % ofthe adefovir patients.[5]

Important Information About BARACLUDE(r)

Discovered at Bristol-Myers Squibb, BARACLUDE(r) is indicated forthe treatment of chronic hepatitis B virus (HBV) infection in adultswith:

- 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 ofcausality) has been observed in patients with decompensated liverdisease, in particular in those with Child-Turcotte-Pugh (CTP) classC disease, compared with rates in patients with compensated liverfunction. In addition, patients with decompensated liver disease maybe at higher risk for lactic acidosis and specific renal adverseevents such as hepatorenal syndrome. Clinical and laboratoryparameters should be closely monitored in this patient population.

* For full prescribing information for BARACLUDE(r), pleaseconsult 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 Bvirus and approximately 350 million people are chronicallyinfected.[6]

About Decompensated Liver Disease

Decompensated liver disease is characterised by failure of theliver to maintain adequate function, often due to severe scarringleading to fibrosis and/or cirrhosis caused by chronic liverinflammation.[1] Symptoms of liver decompensation can include but arenot limited to: jaundice (yellowing of the skin or eyes), ascites(swollen abdomen from abnormal accumulation of fluid), oesophagealvarices (distorted blood vessels that may cause potentially fatalbleeding), and hepatic encephalopathy ( neuropsychiatric abnormalityresulting in personality changes, intellectual impairment and reducedlevels of consciousness).[1]

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical companycommitted to discovering, developing and delivering innovativemedicines that help patients prevail over serious diseases.

BARACLUDE(R) (entecavir) is a registered trademark ofBristol-Myers Squibb Company.

References

1. D'Amico G, Garcia-Tsao G, Pagliaro L. Natural history andprognostic indicators of survival in cirrhosis: a systematic reviewof 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 Disease2006;26(2):142-152.

3. Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellularcarcinoma in cirrhosis: Incidence and risk factors. Gastroenterology2004;127(5 Suppl 1):S35-S50.

4. Fattovich G, Pantalena M, Zagni I et al. Effect of hepatitis Band C virus infections on the natural history of compensatedcirrhosis: a cohort study of 297 patients. Am. J. Gastroenterol.2002; 97: 2886-95.

5. Y. Liaw, et al. Efficacy and Safety of Entecavir versusAdefovir in Chronic Hepatitis B Patients with Evidence of HepaticDecompensation. Abstract and Poster 442. AASLD 2009.

6. World Helath Organization Web site. Fact sheet N- 204.http://www.who.int/mediacentre/factsheets/fs204/en/. Accessed 3December 2010.

ots Originaltext: Bristol-Myers Squibb GmbH & Co.KG aAIm Internet recherchierbar: http://www.presseportal.de

Contact:Contact: Media: Annie Simond, office: +33-1-58-83-65-66,annie.simond@bms.com

Bristol-Myers Squibb GmbH & Co.KG aA

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BARACLUDE(R) (entecavir) Approved by the European Commission for the Treatment of Chronic Hepatitis B in Adult Patients With Evidence of Decompensated Liver Disease

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