Press Report:


LAVAL, Quebec, April 11 /CNW-PRN/ - BioChem Pharma Inc. announces that an interim review of a long-term follow-up study involving 58 Chinese patients with chronic hepatitis B shows that nearly half (47%; 27/58) achieved hepatitis e antigen seroconversion after four years of treatment with Epivir-HBV(R) (lamivudine). Seroconversion, a marker of loss of viral replication, is defined in this study as the loss of hepatitis B e antigen and gain of antibody to e antigen. In previous annual interim

evaluations of this study population, 29% (17/58) of the patients had seroconverted after two years of therapy, 40% (23/58) after three years and, now, 47% after four years of treatment with Epivir-HBV. The data, presented today at the 10th International Symposium on Viral Hepatitis and Liver Disease, also showed that in a subset of 26 patients who entered the study with elevated serum alanine aminotransferase (ALT) levels more than two times above the normal limit, the seroconversion rate was 73% after four years of therapy. These data suggest that elevated pre-treatment serum ALT, a marker of liver inflammation, is associated with increased rates of seroconversion.

The results of this study are important for a variety of reasons, in particular the trend of incremental, steady increase in the number of patients who no longer have clinical evidence of chronic hepatitis B after extended treatment with Epivir-HBV, and the fact that the drug appears to be generally well tolerated for this treatment period,'' said Dr. Ting-Tsung Chang, Professor in the Department of Internal Medicine, at the National Cheng Kung University Hospital (Tainan, Taiwan). ``Seroconversion may predict sustained suppression of hepatitis B virus and improved clinical prognosis.''

The study reported today is a five-year uncontrolled clinical trial involving 58 adult Chinese patients with compensated chronic hepatitis B. Study participants received 100 mg per day of Epivir-HBV. Of the original 58 patients in the study, 44 were still on treatment through four years. Five patients had stopped treatment after three years, and nine additional patients withdrew before the end of year 4. Hepatitis B is an infectious disease that ranges from mild acute infection with no signs or symptoms to a more serious chronic liver disease, which can lead to severe liver scarring (cirrhosis), liver failure or liver cancer. Worldwide, approximately one million people die annually from hepatitis B-associated liver disease. The most important goal of therapy for chronic hepatitis B is reducing the progressive liver inflammation that occurs when the immune system attacks hepatitis B-infected liver cells. Epivir-HBV acts directly to inhibit viral replication, leading to reduced inflammatory response to the hepatitis B virus in the liver.

It was also noted in the study that 39 of 58 (67%) patients developed YMDD variant hepatitis B virus at some point during treatment. YMDD variants have been associated with a diminished treatment response to lamivudine. However, 13 of these 39 patients (33%) achieved HBeAg seroconversion despite having a variant strain of hepatitis B. In six of these patients, seroconversion occurred after detection of the YMDD variants. Also, 23 of the 39 patients who were determined to have the YMDD variant virus had normal ALT levels at their last clinic visit. The long-term clinical significance of YMDD variant hepatitis B is unknown.

The data in this study suggest that the presence of the YMDD variant strain of hepatitis B may not preclude patients from experiencing a clinical benefit from treatment with Epivir-HBV and, in some cases, from experiencing seroconversion,'' said C-L Lai, MD, Co-Chief, Division of Gastroenterology and Hepatology at Queen Mary Hospital, Hong Kong. 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 the 58-patient trial from which the newly presented data are drawn, one patient experienced transient hepatic decompensation coincident with detection of YMDD variant, and remained on therapy. More generally, in clinical trials supporting the approval of Epivir-HBV, 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% (21%); malaise and fatigue, 24% (28%); and headache, 21% (21%). The optimum duration of treatment, 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.

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported 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 as Epivir-HBV Tablets and Oral Solution contain a lower dose of the same active ingredient (lamivudine) as Epivir(R) 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.  Lamivudine for hepatitis B is already available in many countries including China, South Korea, the US, Canada, UK, Germany and France. In most markets the trade name Zeffix is used; in the US it is known as Epivir-HBV; in Canada  as Heptovir and in China as Heptodin.