Reuters Health Information (2005-11-01): Entecavir safe, effective in lamivudine-refractory hepatitis B virus
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
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."