News Release

Yamanouchi Pharmaceutical Co., Ltd.

Yamanouchi and Amgen Launch the Recombinant Interferon-a
Advaferon Injection

December 7, 2001

Tokyo, Japan - December 7, 2001 - Yamanouchi Pharmaceutical Co., Ltd. (president: Toichi Takenaka) and Amgen Limited (president: Fuminori Yoshida) launched today Advaferon Injection [generic name: interferon alfacon-1 (genetical recombination)], a drug for the treatment of chronic hepatitis C. Developed by Amgen Inc. in the US, Advaferon Injection is a new interferon-a (IFN-a) and was co-developed by Yamanouchi and Amgen Limitd. in Japan. It is manufactured and marketed by Yamanouchi in Japan.

Interferon alfacon-1 is a new IFN-a developed by combining different amino acids with high incidence based on the amino acid sequences of 13 IFN-a subtypes. Basic studies have shown that its antiviral activity per mg of protein is greater than that of existing IFN-a products.

In a comparative clinical trial in Japan, Advaferon Injection produced a CR rate (hepatitis C virus eradication rate determined 24 weeks after completion of the treatment) of 16.7% in "hepatitis C patients with genotype 1b and high titer." This rate was clearly higher than the rate achieved by the existing IFN-a product. Particularly high CR rate of 27.5% was obtained in high titer patients with 100-700K copies/mL. A CR rate of 73.3% was obtained in a clinical trial conducted in patients with low titer (less than 100K copies/mL). Major adverse reactions were fever, general malaise and anorexia, similar to those reported for existing IFN products.

The number of hepatitis C patients in Japan is estimated to be no less than 2 million. Liver cirrhosis and liver cancer are caused as a result of the progression of chronic hepatitis C in a great majority of patients. The number of liver cancer patients has been increasing in recent years, and increases are expected to continue until 2010-2020.

The approved indication of Advaferon Injection is "improvement of viremia associated with chronic hepatitis C." It is therefore expected to provide a new therapy for patients with not only genotype 2, low titer but also genotype 1b high titer, which is refractory to existing therapies.

Yamanouchi and Amgen Limited will cooperate further in order to market Advaferon Injection as a competitive IFN for chronic hepatitis C with special emphasis on its advantages over existing IFN products and extensive clinical experience abroad.


Product profile
Brand name: Advaferon Injection 1200 and 1800
Generic name: interferon alfacon-1 (genetic recombinant)
Indication: improvement of viremia associated with chronic hepatitis C
Dosage and administration: Administer Advaferon Injection after confirming that the patient is HCV-RNA positive. In general, administer 12-18 million IU once a day, daily or 3 times a week, by subcutaneous injection to adults.

Yamanouchi Pharmaceutical Co., Ltd.
Established in: April 1923
Headquarters: 2-3-11 Nihonbashi Honcho, Chuo-ku, Tokyo, Japan
Annual sales (consolidated): 458 billion Yen (fiscal year ended in March 2001)
Number of employees (including affiliates): 9,400
President and CEO: Toichi Takenaka
Main businesses: manufacturing, marketing, import and export of drugs, quasi-drugs, foods, and medical devices

Amgen Inc.
Established in: April 1980
Headquarters: One Amgen Center Drive, Thousand Oaks, California, 91320-1799 USA
Annual sales (consolidated): US$ 3,629 million (fiscal year ended in December 2000)
Number of employees (including affiliates): 7,300
Chairman, CEO and President: Kevin W. Sharer
Main businesses: research, development, manufacturing and marketing of drugs

Amgen Limited
Established in: March 1992
Headquarters: 2-31-1 Nihonbashi Hamacho, Chuo-ku, Tokyo, Japan
Capital: 475 million Yen
Shareholder: Amgen Inc. (100%)
President: Fuminori Yoshida
Main businesses: manufacturing, marketing and import of drugs, quasi-drugs, and medical devices and equipment