Phase III Clinical Data on Lamivudine for the Treatment of Hepatitis B.

LONDON and LAVAL, Quebec--(BUSINESS WIRE)--April 10, 1997-- Glaxo Wellcome plc and BioChem Pharma Inc. announce that results from a Phase III clinical study of the investigational drug, lamivudine, in hepatitis B will be presented today in London, U.K., at the annual meeting of the European Association for the Study of the Liver.

The study, involving 358 Asian patients with chronic hepatitis B across centres in Hong Kong, Singapore and Taiwan, demonstrates the significant efficacy of lamivudine in improving liver histology compared to placebo.

Lamivudine is a nucleoside analogue antiviral drug for the treatment of hepatitis B, which is under development by Glaxo Wellcome. The company intends to file for regulatory approval of lamivudine worldwide beginning with filings in Asia later this year. The final results of this study will form part of these applications. This study was designed primarily to assess the long-term effect of lamivudine on improving liver histology, an important indicator of severity and stage of liver disease caused by the body's immune response against liver cells infected with hepatitis B.

These results indicate that over a one year period, improvements in liver histology were demonstrated in a significantly higher percentage of lamivudine patients compared to placebo (67% of patients receiving lamivudine 100 mg orally once daily and 59% of patients receiving lamivudine 25 mg orally once daily, compared to 30% of patients receiving placebo). In addition, fewer lamivudine patients (7% of patients on 100 mg and 10% of patients on 25 mg) had deterioration of liver histology compared to placebo (32%).

Chronic hepatitis B can cause deteriorating liver histology, leading to cirrhosis (severe liver scarring) and liver cancer. Such clinical conditions are due to progressive liver damage. The most important goal of hepatitis B therapy is to reduce liver damage caused by the immune system. An antiviral, such as lamivudine, which reduces viral replication, can reduce the level of immunological activity against infected liver cells and may prevent long-term complications associated with this disease.

The presence of hepatitis B e antigen (HBeAg) in patients with hepatitis B is associated with active viral replication. The study results indicate that 16% of patients on lamivudine 100 mg compared to 4% of patients on placebo converted from being HBeAg positive to HBeAg negative with undetectable hepatitis B virus (HBV) DNA. This response, known as seroconversion, is indicative of the body's immune system mounting an effective response to this viral protein.

Sustained reductions in the levels of HBV DNA in the lamivudine treatment arms mirrored the significant data obtained in the Phase II studies. HBV DNA is an important marker of viral replication and viraemia (the level of virus in the blood).

Marc Rubin, M.D., International Anti-Infectives Immunology Director for Glaxo Wellcome, commented, "While definitive conclusions about the clinical profile of lamivudine must await the further analysis of this study and other Phase III clinical studies currently in progress, these results are extremely encouraging and demonstrate the significant potential lamivudine offers as the first oral anti-HBV therapy with proven histological benefit in the majority of chronically infected hepatitis B patients."

"Today's results from this Phase III study, conducted in a clearly difficult-to-treat group of patients, support lamivudine's potential as a powerful new antiviral therapy for the treatment of chronic hepatitis B infection," said Gervais Dionne, Ph.D., Executive Vice President, Research & Development, BioChem Pharma Inc. "It is particularly encouraging that lamivudine monotherapy over one year significantly improves liver histology and suppresses serum viral load in the majority of these patients."

Lamivudine was discovered by BioChem Pharma of Laval, Quebec, Canada and licensed to Glaxo (now Glaxo Wellcome) in 1990.

Glaxo Wellcome is a research-based company, committed to bringing innovative medicines and services to patients throughout the world and to the healthcare providers who serve them.

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 the NASDAQ National Market (BCHXF).

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

This press release contains forward-looking statements which reflect the company'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 success of the company's research strategy, the applicability of the discoveries made therein, the successful and timely completion of clinical studies and the uncertainties related to the regulatory process. -0-

SOURCE: BioChem Pharma Inc.

DATE: April 10, 1997

SUBJECT: BACKGROUND NOTES

Hepatitis

Hepatitis is a general term denoting inflammation of the liver. It can be caused by a number of agents, including viruses as well as bacteria, protozoa, alcohol, drugs and autoimmune conditions. At least six different hepatitis viruses are known to exist, known as hepatitis A,B,C,D,E & G.

Hepatitis B

Hepatitis B is transmitted through blood and body fluids. When a person is infected with hepatitis B virus (HBV), the virus reaches the liver where it enters individual liver cells. Here it replicates and can re-enter the blood stream as well as infecting other liver cells. The body's response to these infected cells is largely responsible for the inflammation and damage to the liver that follows. The virus itself does not appear to cause any direct damage to the liver. People whose immune systems are not triggered by the virus can become apparently healthy "carriers." Over time they can develop an immune response to the virus and/or liver damage.

About 90 to 95% of newly infected adults develop antibodies to HBV. About 5-10% of newly infected adults and approximately 90% of children and adults infected with HBV at around the time of birth, do not eliminate the virus. These patients develop "chronic" infection which may last from six months to many years and may develop serious liver disease (cirrhosis) and liver cancer.

There are an estimated 300-350 million chronic carriers of hepatitis B virus, of whom 95% are in the developing world (particularly Asia). Approximately 1-2 million deaths a year are attributable to hepatitis B.

Liver Histology

Liver histology is a technique for assessing the level of liver damage in patients infected with hepatitis B virus (HBV). HBV-induced immunological activity is the primary cause of liver damage associated with hepatitis B infection. Deteriorating liver histology indicates progressive liver disease which can lead to fatal cirrhosis and liver cancer. Liver histology is usually measured by taking liver biopsies (small pieces of liver tissue) which are stained and examined under a microscope. The biopsy is scored according to a recognized and accepted scoring system (Knodell Histological Activity Index) for inflammation, necrosis (cell death) and fibrosis. This activity index and the individual components are used to determine the severity and stage of the infection. Pre and post treatment biopsies are examined to assess the impact of treatment on the liver.

Seroconversion

When a foreign protein is recognized by the immune system, antibodies are produced which can sometimes subsequently clear the protein from the blood. This process -- disappearance of the antigen concomitant with the emergence of antibodies -- is seroconversion. In hepatitis B, the term seroconversion refers to hepatitis B e-antigen (HBeAg) seroconversion. In the natural course of hepatitis B, HBeAg seroconversion usually predicts viral clearance and clinical disease remission, although some HBeAg seroconverters do revert and active disease resumes. Therefore, loss of detectable antigen without appearance of antibodies is not equivalent to a cure. Individuals may also seroconvert to hepatitis B surface antigen (HBsAg), which is a more definitive indicator of long-term viral clearance and clinical remission.

HBV DNA

HBV is a DNA (deoxyribonucleic acid) virus. HBV DNA is an important marker of viral replication and viraemia (the level of the virus in the blood stream).

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