Basel, 27 October 2003

Long-term data shows MabThera to be a highly promising treatment for Rheumatoid Arthritis (RA)
Extended data from phase II study shows RA patients continue to respond to MabThera for up to 48 weeks

Roche, Genentech and IDEC Pharmaceuticals Inc. today announced positive results from an extended Phase II study showing that a single, short course of treatment (two doses) with MabThera (rituximab) significantly improved symptoms in patients with severe rheumatoid arthritis (RA) for up to 48 weeks*.
In the study, investigators followed up with patients who had completed a 24-week clinical trial, in order to assess duration of response with MabThera beyond the initial endpoint of 24 weeks. Participants in the 24 week, four arm, placebo controlled trial were randomized to receive MabThera alone or in combination with cyclophosphamide or methotrexate (MTX), as compared to patients receiving MTX alone.

At 48 weeks, patients receiving the combination of MabThera and MTX had the greatest improvement in symptoms:
• 65% of patients showed at least a 20% improvement in symptoms
• 35% showed at least a 50% improvement
• 15% showed at least a 70% improvement.

“These data indicate that selectively targeting B cells is a promising and innovative potential therapeutic approach for the treatment of rheumatoid arthritis,” said Professor Paul Emery, Leeds General Infirmary, UK, one of the trial’s key investigators. “With just two doses of MabThera, patients continued to respond to treatment for up to 48 weeks.”

About the Study

The study included 161 patients with active, long-standing RA (mean 10.4 years) who had not responded or responded inadequately to multiple other therapies. Patients were randomized into one of four treatment groups. The first group continued receiving methotrexate (MTX) alone (³ 10 mg weekly), the second group received MabThera alone (2 infusions of 1g), the third group received MabThera (2 infusions of 1g) in combination with cyclophosphamide (2 infusions of 750 mg) and the fourth group received MabThera (2 infusions of 1g) in combination with MTX (³ 10 mg weekly). Each group also received a 17-day course of corticosteroids (total dose of 960 mg). MabThera was infused intravenously on days one and 15 of the study – no further treatment with MabThera was given.

Results from the other three arms of the study include:

• MTX alone: 20% of patients experienced a 20% improvement in symptoms and 5% experienced 50% improvement; none experienced 70% improvement
• MabThera alone: 30% experienced 20% improvement, 13% experienced 50% improvement and 8% experienced 70% improvement
• MabThera and cyclophosphamide: 44% experienced 20% improvement, 22% experienced 50% improvement and 10% experienced 70% improvement

According to the investigators, the study’s safety profile indicates that all three MabThera regimens were well tolerated with similar levels and type of adverse events compared to MTX alone. A large proportion of events were reported during the initial 15 days, with many associated with the first MabThera infusion. The majority of events were of mild to moderate in intensity. At week 48, the incidence and types of events, including infections, were evenly balanced between all groups.

Ongoing Studies
Based on these exciting phase II results, Roche has initiated pivotal trials evaluating MabThera in the treatment of RA, including a phase III study for patients who have had an inadequate response to anti-TNF therapies (REFLEX) and a phase IIb study for patients who have had an inadequate response to DMARDs (DANCER) Both of these trials are currently enrolling patients.

About MabThera
MabThera (rituximab) is a therapeutic antibody that selectively targets B cells, which are thought to play a key role in the inflammatory cascade of RA – a series of reactions inflaming the synovia and leading to the cartilage loss and bone erosion that is characteristic of the disease.
MabThera is currently indicated for use in the treatment of the most common form of blood cancer, non-Hodgkin's lymphoma (NHL) and marketed by Roche and Genentech, and was developed by IDEC and Genentech. MabThera/ Rituxan is marketed in Europe as MabThera and in the US, Canada and Japan as Rituxan. Approx. 300,000 patients have received MabThera to date.

About rheumatoid arthritis
RA affects almost 6 million people around the world, up to 2 million of which are in Europe, and is a debilitating disease that hinders the daily activities of sufferers. RA is characterized by inflammation of multiple joints, cartilage loss and bone erosion, which leads to joint destruction and ultimately reduced joint function. Additionally, since RA is a systematic disease, it can have effects in other tissues, such as lungs, eyes and bone marrow. After ten years of RA, fewer than 50% of patients can continue to work or function normally on a day to day basis.

About Roche
Headquartered in Basel, Switzerland, Roche is one of the world’s leading innovation-driven healthcare groups. Its core businesses are pharmaceuticals and diagnostics. Roche is number one in the global diagnostics market and is the leading supplier of pharmaceuticals for cancer and a leader in virology and transplantation. As a supplier of products and services for the prevention, diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people’s health and quality of life. Roche employs roughly 65,000 people in 150 countries. The Group has alliances and research and development agreements with numerous partners, including majority ownership interests in Genentech and Chugai. Please visit www.roche.com for further information.

About Genentech
Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes biotherapeutics for significant unmet medical needs. Fifteen of the currently approved biotechnology products originated from or are based on Genentech science. Genentech manufactures and commercializes ten biotechnology products in the United States. The company has headquarters in South San Francisco, California and is traded on the New York Stock Exchange under the symbol DNA. For press releases and additional information about the company, please visit http://www.gene.com.

About IDEC
IDEC Pharmaceuticals focuses on the commercialization and development of targeted therapies for the treatment of cancer and autoimmune diseases. IDEC's antibody products act chiefly through immune system mechanisms, exerting their effect by binding to specific, readily targeted immune cells in the patient's blood or lymphatic systems. IDEC is headquartered in San Diego, California, and is traded on the NASDAQ National Market System under the stock symbol, IDPH.

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* The study was presented during an oral session at the annual scientific meeting of the American College of Rheumatology (ACR) Meeting, October 24-28.