The nucleoside analogue entecavir has been approved by the Food and Drug Administration for treating chronic hepatitis B in adults with decompensated liver disease, the manufacturer announced.

Approval was based on data from an ongoing study that randomized patients with chronic hepatitis B and decompensated liver disease to treatment with entecavir, at a dose of 1 mg once daily, or the nucleotide analogue adefovir (10 mg once daily), according to a statement issued by Bristol-Myers Squibb (BMS).

Entecavir, first approved by the FDA in 2005 for treating chronic hepatitis B in adults with compensated liver disease, is marketed as Baraclude by BMS.

The open label, controlled, phase 3b study enrolled HBeAg-positive or HBeAg-negative patients with chronic hepatitis B and evidence of hepatic decompensation, who had never been treated for hepatitis B virus (HBV) or had been treated predominantly with lamivudine or interferon-alpha; 100 patients were randomized to receive entecavir, 91 to receive adefovir.

At 48 weeks, 57% of the patients in the entecavir arm had an undetectable HBV DNA viral load (less than 300 copies/mL), compared with 20% of those on adefovir, according to BMS. Among the patients with abnormal alanine aminotransferase levels at baseline, more of those treated with entecavir achieved normal levels at 48 weeks, compared with those treated with adefovir (63% vs. 46%, respectively). Loss of hepatitis B surface antigen was seen in 5% of those on entecavir, compared with none of those treated with adefovir.

However, slightly more patients on adefovir (67%) showed improvement, or no worsening, in their Child-Turcotte-Pugh scores, compared with 61% of those on entecavir.

The most common adverse events reported in patients treated with entecavir through 48 weeks were peripheral edema (16%), ascites (15%), pyrexia (14%), hepatic encephalopathy (10%), and upper respiratory infection (10%), according to the company statement.

The study is the ETV-048 trial.

Approved in 2002, adefovir (Hepsera) is indicated for the treatment of chronic hepatitis B in patients 12 years of age and older with evidence of active viral replication and either persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.

10/28/10