The latest research & treatment news about Hepatitis C infection, diagnosis, symptoms and treatment.

November 9, 1998

LAMIVUDINE SIGNIFICANTLY ALLEVIATES LIVER DISEASE IN PATIENTS WITH CHRONIC HEPATITIS B

LAVAL, Quebec /CNW-PRN/ – BioChem Pharma Inc. (NASDAQ: BCHE; ME, TSE: BCH) announced that new data presented this week at the American Association for the Study of Liver Diseases (AASLD) meeting in Chicago, demonstrate that treatment with lamivudine (Zeffix) – a breakthrough oral anti-viral treatment for chronic Hepatitis B, discovered by BioChem Pharma and developed by Glaxo Wellcome, leads to sustained improvements in liver inflammation.(1)

Hepatitis B is a potentially fatal liver disease and one of the most common infectious diseases in the world. Approximately 350 million people are chronic carriers of Hepatitis B and nearly one third of these are expected to develop serious progressive liver disease, leading to liver cirrhosis (severe liver scarring) and liver cancer.

The results from several key lamivudine studies are being presented at the meeting. Today, Professor Nancy Leung of the Prince of Wales Hospital, Hong Kong, is presenting data from a subset of patients who received 100 mg of lamivudine once daily for two years. These data were part of a large Asian multicentre study. Liver biopsies were performed before treatment, and after one and two years of treatment, to assess the extent of liver damage caused by Hepatitis B infection. The biopsies assessed the growth of fibrous tissue within the liver (liver fibrosis) and the extent of cell damage or death and inflammation (measured as necro-inflammatory index score). Serum markers of Hepatitis B infection were also measured, including levels of Hepatitis B virus DNA (HBV DNA, a marker of viral replication) and levels of the enzyme alanine transaminase (ALT, released by damaged liver cells and used as a marker for liver cell damage).

The results after two years of lamivudine monotherapy showed continued improvements in liver biopsy samples – reductions were seen in cell damage, death and inflammation, and in the degree of liver fibrosis. The improvements in liver biopsy samples seen in year two were greater than those seen after the first year of treatment and were all consistent with ongoing suppression of HBV DNA and continued normalisation of serum ALT levels – an indication of liver activity returning to normal.

Professor Leung commented on the studies: “These results show that lamivudine reverses the progression of liver disease and improves the condition of the liver in a broad range of patients with chronic Hepatitis B.”

An analysis of the combined data from four Phase III clinical assessed the effectiveness of lamivudine treatment in patients who developed variant HBV strains, which appear in the laboratory to be less susceptible to the product.(2) Of the 558 patients treated with 100 mg once daily lamivudine for one year in the trials, 16-32% developed detectable levels of such viral strains. Analyses of the combined clinical trial data indicated that such patients still showed significant improvements in liver disease as well as reductions in serum ALT levels and continued suppression of HBV DNA (median 80% decrease) when compared to placebo controls. These data further support the broad utility of lamivudine for treating a range of patients with chronic Hepatitis B, including the subgroup of patients who eventually develop the variant HBV strains associated with lamivudine resistance in laboratory assays. Studies are currently ongoing worldwide to evaluate longer-term clinical outcomes in lamivudine- treated Hepatitis B patients.

A second analysis of the combined data from the four Phase III trials, being presented by Professor Nancy Leung, assesses the overall safety profile of lamivudine. This indicates that the side effects of lamivudine were similar to placebo during the one year Phase III treatment periods. Analysis of controlled post treatment data indicate a modest increase in post treatment ALT elevations in the lamivudine group; however, there was no difference in clinically severe post treatment events in the lamivudine and placebo groups.(3)

These data indicate that lamivudine is also a well-tolerated treatment for chronic Hepatitis B with only a minor effect on ALT seen after therapy,” Professor Leung concluded.

The established treatment for chronic Hepatitis B infection is interferon therapy, which is uncomfortable for patients to self-administer (by injection), can be associated with unpleasant side effects, and only produces a lasting response in one third or less of those treated. Interferon is used therapeutically to stimulate the immune system. In contrast, lamivudine acts directly on the Hepatitis B virus and suppresses viral replication.

The efficacy of lamivudine is well-established. Data published in The New England Journal of Medicine in July 19984 showed that treatment with lamivudine for one year was associated with substantially reduced liver inflammation and enhanced HBeAg seroconversion compared to placebo. HBeAg seroconversion is an indication of long- term remission of the disease. Further data presented by Professor Eugene Schiff from the University of Miami, USA, at the International Association for the Study of the Liver (IASL), on Wednesday, November 4, demonstrated the long-term durability of HBeAg seroconversion in patients whose lamivudine treatment was discontinued.(5) With an average follow-up of more than six months after treatment was discontinued, over 90% of patients maintained their seroconverted status off-treatment by the time of the last available data. Long-term data from other published studies of HBeAg- seroconverted patients suggest that this group is likely to experience improved long-term clinical outcomes, with reduced incidence of cirrhosis, liver failure and death.

The first approval of lamivudine was received in the Philippines in August 1998 followed by New Zealand in September 1998. Regulatory applications have been submitted in a number of countries worldwide, including China, Hong Kong, Singapore, Japan, Canada, the USA and Europe.

Under the terms of a license agreement, BioChem Pharma will receive royalties from Glaxo Wellcome on sales of lamivudine. Glaxo Wellcome has the right to develop, manufacture and sell lamivudine worldwide, subject to special arrangements for Canada, where BioChem Pharma and Glaxo Wellcome have formed a commercialization partnership.

BioChem Pharma is an international biopharmaceutical company dedicated to the research, development and commercialization of innovative products for the prevention, detection and treatment of human diseases. The Company lists its common shares on the Montreal and Toronto exchanges (BCH) and on the NASDAQ National Market (BCHE).

Zeffix is a trade mark of the Glaxo Wellcome group of companies.

BioChem Pharma news releases and other company information can be found on the World Wide Web at http://www.biochempharma.com.

This press release contains forward-looking statements, which reflect the Corporation’s current expectation regarding future events. The forward-looking statements involve risks and uncertainties. Actual events could differ materially from those projected herein and depend on a number of factors, including the successful and timely completion of clinical studies and the uncertainties related to the regulatory process. Investors should consult the Corporation’s ongoing quarterly filings, annual reports and 20-F filings for additional information on risks and uncertainties relating to these forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. The Corporation disclaims any obligation to update these forward-looking statements.

REFERENCES:

1. Abstract No. 1307. Hepatology 1998 (suppl) 28; 4 pt 2, p 489A

2. Abstract No. 625. Hepatology 1998 (suppl) 28; 4 pt 2, p 319A

3. Abstract No. 1698. Hepatology 1998 (suppl) 28; 4 pt 2, p 587A

4. Lai CL, Chien RN, Leung NWY et al. A one year trial of lamivudine for chronic Hepatitis B. N Eng J Med 1998; 339: 61-68

5. Abstract No. 1. Hepatology 1998 (suppl) 28; 4 pt 2, p 163A

C. Lennon / M. Roy (Media)

C. Lennon / K. Eugeni (Investors)

Corporate Communications

(450) 978-7771

E-mail: corpcom(at)biochempharma.com

Source BioChem Pharma Inc.