Baraclude (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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http://www.therapeuticsdaily.com/news/article.cfm?contentValue=765002 & contentTyp\

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Baraclude (entecavir) Approved by the European Commission for the Treatment of

Chronic Hepatitis B in Adult Patients With Evidence of Decompensated Liver

Disease

From the PharmaLive.com News Archive - Mar. 01, 2011

PARIS, March 1, 2011 /PRNewswire-FirstCall/ -- 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.

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 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® in October 2010.

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.[1] 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.[1] 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 Jorg sen. " The

data used to support this indication shows that BARACLUDE® 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® (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.

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.

Patients were randomised to receive BARACLUDE® (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® 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%).[5]

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 adefovirpatientsand

discontinuations due to adverse events occurred in 7% of the Baraclude patients

and 6 % of the adefovir patients.[5]

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:

- 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®, 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.[6]

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.[1] 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 of

consciousness).[1]

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.

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

Company.

References

1. D'Amico G, -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.

http://www.who.int/mediacentre/factsheets/fs204/en/. Accessed 3 December 2010.

SOURCE Bristol-Myers Squibb

[Guest guest]

http://www.therapeuticsdaily.com/news/article.cfm?contentValue=765002 & contentTyp\

e=newsarchive & channelID=26

Baraclude (entecavir) Approved by the European Commission for the Treatment of

Chronic Hepatitis B in Adult Patients With Evidence of Decompensated Liver

Disease

From the PharmaLive.com News Archive - Mar. 01, 2011

PARIS, March 1, 2011 /PRNewswire-FirstCall/ -- 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.

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 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® in October 2010.

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.[1] 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.[1] 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 Jorg sen. " The

data used to support this indication shows that BARACLUDE® 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® (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.

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.

Patients were randomised to receive BARACLUDE® (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® 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%).[5]

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 adefovirpatientsand

discontinuations due to adverse events occurred in 7% of the Baraclude patients

and 6 % of the adefovir patients.[5]

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:

- 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®, 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.[6]

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.[1] 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 of

consciousness).[1]

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.

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

Company.

References

1. D'Amico G, -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.

http://www.who.int/mediacentre/factsheets/fs204/en/. Accessed 3 December 2010.

SOURCE Bristol-Myers Squibb

[Guest guest]

http://www.therapeuticsdaily.com/news/article.cfm?contentValue=765002 & contentTyp\

e=newsarchive & channelID=26

Baraclude (entecavir) Approved by the European Commission for the Treatment of

Chronic Hepatitis B in Adult Patients With Evidence of Decompensated Liver

Disease

From the PharmaLive.com News Archive - Mar. 01, 2011

PARIS, March 1, 2011 /PRNewswire-FirstCall/ -- 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.

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 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® in October 2010.

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.[1] 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.[1] 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 Jorg sen. " The

data used to support this indication shows that BARACLUDE® 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® (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.

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.

Patients were randomised to receive BARACLUDE® (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® 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%).[5]

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 adefovirpatientsand

discontinuations due to adverse events occurred in 7% of the Baraclude patients

and 6 % of the adefovir patients.[5]

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:

- 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®, 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.[6]

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.[1] 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 of

consciousness).[1]

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.

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

Company.

References

1. D'Amico G, -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.

http://www.who.int/mediacentre/factsheets/fs204/en/. Accessed 3 December 2010.

SOURCE Bristol-Myers Squibb

[Guest guest]

http://www.therapeuticsdaily.com/news/article.cfm?contentValue=765002 & contentTyp\

e=newsarchive & channelID=26

Baraclude (entecavir) Approved by the European Commission for the Treatment of

Chronic Hepatitis B in Adult Patients With Evidence of Decompensated Liver

Disease

From the PharmaLive.com News Archive - Mar. 01, 2011

PARIS, March 1, 2011 /PRNewswire-FirstCall/ -- 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.

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 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® in October 2010.

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.[1] 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.[1] 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 Jorg sen. " The

data used to support this indication shows that BARACLUDE® 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® (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.

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.

Patients were randomised to receive BARACLUDE® (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® 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%).[5]

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 adefovirpatientsand

discontinuations due to adverse events occurred in 7% of the Baraclude patients

and 6 % of the adefovir patients.[5]

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:

- 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®, 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.[6]

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.[1] 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 of

consciousness).[1]

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.

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

Company.

References

1. D'Amico G, -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.

http://www.who.int/mediacentre/factsheets/fs204/en/. Accessed 3 December 2010.

SOURCE Bristol-Myers Squibb