Bristol-Myers Squibb Company

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 liver function.²

 

ETV-048 Study

 

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 (18/91), respectively.¹

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)].¹

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.¹

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).¹

 

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).¹ 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.