Promising Results in Phase II Study of Treatment with Pegasys in HBEAG Positiv

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Experimental Drug Entecavir May Broaden Hepatitis B Armamentarium



By Paula Moyer



The investigative antiviral agent entecavir (Bristol-Myers Squibb) has the potential to broaden physicians' options for treating hepatitis B virus (HBV) infection, according to study results presented at the 52nd annual meeting of the American Association for the Study of Liver Diseases (AASLD).



"Approximately 20% of patients either have a suboptimal initial response [to lamivudine [Epivir HBV] or an 'escape variance'," Dr. Eugene Schiff noted in an interview with Reuters Health. "That is, they go on to acquire a suboptimal response," he said. "Escape variances are typically seen after 9 months of lamivudine therapy. Entecavir, as well as other agents, is being investigated to address the needs of such patients."



Dr. Schiff moderated a panel at which several researchers presented findings on anti-HBV agents. The results of a phase II trial on entecavir were presented by Dr. Stefanos Hadziyannis, a hepatologist practicing in Athens, Greece. Dr. Schiff, a hepatologist at the University of Miami and the president of AASLD, served as one of the trial investigators.



The investigators followed 181 patients who were viremic on lamivudine. The subjects were randomized to receive a daily dose of 0.1 mg, 0.5 mg, or 1 mg of entecavir, or to continue on lamivudine, for 52 weeks.



At 24 weeks, 19% of the patients on 0.1 mg of entecavir had undetectable levels of HBV DNA. Among those on the 0.5-mg dose, the rate was 53%; the rate was 79% for those on the 1-mg dose. Among those continuing on lamivudine, 13% had undetectable DNA levels of the virus.



The investigators also saw assessed the return to normal alanine aminotransferase (ALT) levels. For the 0.1-mg group, the rate of return to normal ALT was 37%. Among the 0.5-mg and 1-mg groups, 60% and 36% returned to normal levels, respectively. In the lamivudine group, the rate was 21%.



"With investigative agents for HBV, we want to know not only how many patients achieve seroconversion, but how many develop an escape variance," Dr. Schiff told Reuters Health. "The follow ups with the newer agents are still too short for us to know. We also want to know if any of these new approaches clear HBV from hepatic cells as well as from blood. As long as the virus remains sequestered in hepatic cells, it has the potential to be reactivated."



The investigators concluded, "In patients failing lamivudine therapy, entecavir significantly decreases hepatitis B viremia, indicating that it represents an important advance in the therapeutic options for patients with hepatitis B. Entecavir was generally well tolerated and had a safety profile similar to that of lamivudine."



Phase III trials of entecavir are currently being planned.



11/16/01