Drug & Device Development

Entecavir safe, effective in lamivudine-refractory hepatitis B virus

Last Updated: 2005-11-01 11:00:03 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Entecavir is safe and effective in patients with chronic hepatitis B virus (HBV) infection who have developed resistance to lamivudine, with 1.0 mg daily being the most effective dose, according to a new phase 2 study.

In vitro studies have shown entecavir, which has no effect on mitochondrial DNA synthesis, is potent against lamivudine-resistant strains of HBV, Dr. Tsing-Tsung Chang of the National Cheng Kung University Medical College in Tainan, Taiwan and colleagues write in the October issue of Gastroenterology. Studies in nucleoside-na�ve patients also have shown the newer drug is effective in reducing HBV DNA levels.

The researchers conducted the current multicenter study to investigate the effect of entecavir in lamivudine-refractory HBV infection. The study included 182 patients who remained viremic after 24 or more weeks on lamivudine. Patients were randomized to continued lamivudine or 1.0, 0.5 or 0.1 mg of entecavir daily for up to 76 weeks.

Twenty-four weeks after the start of the study, 79% of patients on 1.0 mg entecavir had undetectable HBV DNA, compared to 51% of those on 0.5 mg entecavir and 13% of those taking lamivudine.

A complete response, defined as having undetectable HBV DNA, normal ALT levels and being negative for hepatitis B c antigen, had occurred at week 48 in 29% of patients on 1.0 mg entecavir, 19% of patients on 0.5 mg entecavir, and 4% of patients on lamivudine.

Adverse event frequency was the same across all four treatment groups, and most such events were mild to moderate in severity.

"The relatively low seroconversion and complete response rates may be due to impaired host immune response or alterations in the lamivudine-resistant virus and suggest that the optimal duration of antiviral therapy in this population is greater than the 48 weeks evaluated in this study," Dr. Chang and colleagues write.

They conclude: "Entecavir 1.0 mg daily showed the most profound and consistent antiviral activity together with tolerability comparable to lamivudine, making it the most appropriate dose for the treatment of lamivudine-refractory HBV infection."

Gastroenterology 2005;129:1198-1209.