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| |  Study Shows Efficacy Of Oral Epivir-HBV In Hepatitis B RESEARCH TRIANGLE PARK, N.C. -- October 21, 1999 -- Patients with chronic hepatitis B treated with oral Epivir®-HBV™ (lamivudine) were more likely to experience improvements in liver inflammation and other signs of hepatitis B virus infection than patients receiving placebo, according to results of a study published today in the New England Journal of Medicine. Hepatitis B is a potentially fatal liver disease and has been estimated by the World Health Organization to be the ninth most common cause of death worldwide. Approximately 350 million people, five percent of the world’s population, have chronic infection with hepatitis B virus (HBV) and about one-third of these individuals are at risk of serious progressive liver disease. In the United States, the Centers for Disease Control has estimated that there are more than one million persons chronically infected with HBV, and it is estimated that only a small percentage of the patients with active disease have been treated. With hepatitis B, progressive inflammation and scarring of the liver are seen primarily in patients who have persistently high levels of replication of HBV, indicated by the presence of high levels of viral DNA and a viral protein (known as HBV "e antigen") in blood samples. Consequently, the goal of antiviral therapy for patients with hepatitis B is to substantially reduce levels of HBV replication. Suppression of viral replication is thought to reduce harmful liver inflammation resulting from the body’s immune reaction to HBV infection. This randomized, double-blind, placebo-controlled clinical study of the antiviral Epivir-HBV, an oral antiviral therapy, involved 143 previously untreated adults with compensated chronic hepatitis B who were enrolled at 34 clinical centers in the United States. Sixty-six patients receiving Epivir-HBV and 71 patients receiving placebo were included in the efficacy analyses. The author of the study were Dr. Jules Dienstag, of Massachusetts General Hospital/Harvard Medical School, and co-authors from participating clinical centers. Among patients receiving Epivir-HBV (100 mg once daily for one year), 52 percent achieved significant improvements in liver inflammation, compared to 23 percent of patients receiving placebo at one year. Also, patients treated with Epivir-HBV were significantly more likely to have a decrease in blood levels of HBV DNA to below the detection limit of the test that was used. An additional indicator of loss of viral replication, e antigen seroconversion (defined as loss of e antigen, gain of e antibody, and loss of detectable serum HBV DNA) was observed in 17 percent of patients treated with Epivir-HBV compared to 6 percent of patients treated with placebo. Seventy-three percent of patients treated with Epivir-HBV who achieved e antigen seroconversion maintained this response to the end of the 16-week follow-up period. Additional study findings included sustained normalization of ALT (a serum marker of liver inflammation) in 41 percent of patients treated with EPIVIR-HBV as compared to 7 percent in the placebo group. Safety observations in the present study indicated treatment with Epivir-HBV was generally well-tolerated. Epivir-HBV and placebo were associated with similar side effects during the study period. After stopping treatment, patients receiving Epivir-HBV had a higher rate of transient ALT elevations, but in this study clinically severe post-treatment effects were infrequent and not different in incidence following either Epivir-HBV or placebo (see below for further information on post-treatment experience). In conjunction with the earlier New England Journal report of Lai et al. (NEJM July 9, 1998), the current study suggests that the effects of lamivudine therapy are similar in Western and Asian patients. "The results of this and other studies indicate that lamivudine (Epivir-HBV) treatment is generally well-tolerated and may produce substantial benefits in chronic hepatitis B patients. Additionally, the current results indicate that hepatitis B e antigen responses experienced by patients receiving Epivir-HBV were maintained by most patients during the 4-month follow-up period after treatment," said Dr. Dienstag, the principal author of the current study. Epivir-HBV is an oral medication, dosed with one tablet daily (100 mg), that is indicated for the treatment of adults with compensated chronic hepatitis B associated with evidence of hepatitis B viral replication and active liver inflammation. In clinical trials including the present study, Epivir-HBV was generally well-tolerated among chronic hepatitis B patients. In three placebo-controlled clinical trials, the most common adverse events observed in patients treated with Epivir-HBV (vs. placebo) were ear, nose and throat infections, 25 percent (21 percent); malaise and fatigue, 24 percent (28 percent); and headache, 21 percent (21 percent). The optimum duration of treatment with Epivir-HBV, the durability of HBeAg seroconversions occurring during treatment, and the relationship of initial treatment response to outcomes such as hepatocellular carcinoma and decompensated cirrhosis are not known. The reappearance of assay-detectable HBV DNA during lamivudine treatment was observed in approximately one third of patients after initial response. Post-treatment exacerbations of hepatitis B have occurred. Most events appear to be self-limiting. Fatalities have been reported in some cases. The causal relationship to discontinuation of lamivudine treatment is unknown. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported rarely with the use of nucleoside analogues alone or in combination, including lamivudine and other antiretrovirals. Human immunodeficiency virus (HIV) counseling and testing should be offered to all patients before beginning Epivir-HBV and periodically during treatment, because Epivir-HBV tablets and Oral Solution contain a lower dose of the same active ingredient (lamivudine) as Epivir® Tablets and Oral Solution used to treat HIV infection. If treatment with Epivir-HBV is prescribed for chronic hepatitis B for a patient with unrecognized or untreated HIV infection, rapid emergence of HIV resistance is likely because of subtherapeutic dose and inappropriate monotherapy. Epivir-HBV was discovered by BioChem Pharma, Inc., of Laval, Quebec, and licensed to Glaxo Inc. (now Glaxo Wellcome Inc.) in 1990.
Related Links: lamivudine and BioChem Pharma Inc.
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