The New England Journal of Medicine Publishes Research Examining PEGASYS -peginterferon alfa-2a-, Investigational Hepatitis C Therapy.

Business & Health Editors

NUTLEY, N.J.--(BUSINESS WIRE)--Dec. 7, 2000

Two studies published in today's edition of The New England Journal of Medicine feature clinical data about PEGASYS(R) (peginterferon alfa-2a), an investigational treatment for hepatitis C.

A blood-borne virus, hepatitis C is the leading cause of cirrhosis and liver cancer in the United States. PEGASYS, a once-weekly, pegylated form of interferon, is currently under review by the U.S. Food and Drug Administration for the treatment of hepatitis C.

The data was collected from two clinical trials:

1. Phase III trial comprised of 531 patients with and without

cirrhosis. Treatment with PEGASYS was compared to treatment with

interferon alfa-2a, with all patients receiving 48 weeks of

treatment followed by a 24 week post-treatment follow-up period

to determine sustained viral response (SVR). Sixty percent of

patients in this study were infected with genotype 1, the most

prevalent genotype in the United States as well as the most

resistant to currently available treatments.

2. The first Phase II/III study exclusively examining patients in

which the hepatitis C virus had caused liver scarring, or

cirrhosis. The study followed 271 patients, randomized to receive

either PEGASYS or interferon alfa-2a, for 48 weeks of treatment

followed by 24 weeks of follow-up.

"PEGASYS could be an important new therapy for many of the 2.7 million Americans who are infected with hepatitis C and have had limited treatment options to consider," said Chris Pappas, M.D., medical director at Hoffmann-La Roche, developer of PEGASYS. "PEGASYS is the result of more than a decade of Roche original research into pegylated interferon. Its development is particularly important now, at a time when hepatitis C has emerged as a major public health concern."

The most common serious adverse events reported for PEGASYS, observed in clinical studies to date, were infections, psychiatric disorders and gastrointestinal disorders. The most common adverse events include fatigue, headache, myalgia/arthralgia, flu-like symptoms, nausea/vomiting, injection site reactions, fever, chills, diarrhea, partial alopecia, abdominal pain, depression, irritability, insomnia, dizziness and anorexia.

About Pegylation

Pegylation is the attachment of one or more chains of polyethelene glycol (also known as PEG) to another molecule. In PEGASYS, a 40 kilodalton branched, mobile PEG is covalently bound to the interferon alfa-2a molecule and provides a selectively protective barrier, without significantly reducing binding site receptivity. Pharmacokinetic behavior of a pegylated molecule depends on the size of the PEG and the structure of the link between the PEG moiety and the protein.

Researchers believe the PEG creates a barrier that shields the interferon alfa-2a molecule from being rapidly degraded by proteases in the body and maintains its ability to consistently suppress the hepatitis C virus over the one-week dosing period. Specifically, clinical trials have demonstrated that drug levels following a single dose of PEGASYS last more than one full week (168 hours).

Preliminary pre-clinical and human volunteer data suggest that the high molecular weight (40 kilodalton) branched PEG in PEGASYS helps provide sustained pegylated interferon alfa-2a exposure at clinically significant levels over the one-week dosing period. In contrast, according to earlier Roche studies using smaller PEGs developed by the company, interferons with smaller PEGs are degraded quickly, requiring more frequent dosing.

About Hepatitis C

Hepatitis C, a blood-borne infectious disease of the liver, is a leading cause of cirrhosis and liver cancer and the number-one reason for liver transplants in the U.S. An estimated 2.7 million Americans are chronically infected with the virus, with approximately 35,000 new infections each year. In the United States, the Centers for Disease Control and Prevention estimate that hepatitis C is responsible for eight to ten thousand deaths per year and could increase to 38,000 by the year 2010.

Hepatitis C is a blood-borne virus transmitted through body fluids, primarily blood or blood products, and sharing needles. In many patients, the mode of transmission is unknown. Unfortunately, most people who are infected with hepatitis C are unaware of it because it may take years for symptoms to develop.

About Hoffmann-La Roche

Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S. prescription drug unit of the Roche Group, a leading research-based health care enterprise that ranks among the world's leaders in pharmaceuticals, diagnostics and vitamins. Roche discovers, develops, manufactures and markets numerous important prescription drugs that enhance people's health, well-being and quality of life. Among the company's areas of therapeutic interest are: virology, including HIV/AIDS and hepatitis C; infectious diseases, including influenza; cardiology; neurology; oncology; transplantation; dermatology; and metabolic diseases, including obesity and diabetes.

For more information on the Roche pharmaceuticals business in the United States, visit the company's web site at: http://www.rocheusa.com