Basel, 28 October 2003

359 Patient, Phase II Clinical Study Results of MRA, A Beneficial Treatment for Adult Rheumatoid Arthritis
67th Annual Scientific Meeting of the American College of Rheumatology

Roche and Chugai Pharmaceutical Co., Ltd. (Chugai) announced today the results of a completed, large, double-blind, randomized Phase II clinical study with MRA, involving over 350 adult patients with rheumatoid arthritis (RA), which showed MRA to be a potentially effective treatment for adult RA. MRA is a humanized anti-interleukin-6 receptor antibody that inhibits the function of the cytokine interleukin-6 (IL-6). IL-6 is well recognized as playing a central role in the inflammatory response.

This large Phase II study was designed to evaluate the safety and efficacy of a range of doses of MRA given alone, and in combination with methotrexate (MTX) for the treatment of adult RA. Efficacy endpoints included Disease Activity Score (DAS) and the associated EULAR response, as well as the normalization of inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels. A total of 359 patients with active RA, with an inadequate response to MTX, were randomized to one of seven treatment arms of intravenous infusions of MRA 2, 4, or 8 mg/kg every 4 weeks either as monotherapy, or in combination with MTX, or MTX plus MRA placebo.

MRA improved DAS scores and EULAR response in monotherapy and combination therapy with MTX. Efficacy was achieved at 8 mg/kg. Efficacy was also seen with 4 mg/kg doses, in combination with MTX. In addition, MRA induced favorable, dose-related changes in mean clinical and laboratory values reflective of disease improvement - both CRP and ESR. These levels became normal in both 8 mg/kg monotherapy and in 8 mg/kg combination therapy.
MRA was well tolerated as both a mono and combination therapy and the safety profile was consistent with that expected for other biologics. To date, over 500 adult RA patients have been treated with MRA in both Europe and Japan.

Professor Sir Ravinder Maini of The Kennedy Institute of Rheumatology, London stated, “The targeted blockade of the IL-6 signal represents an additional and potentially effective treatment option for adult RA, and the results of this large Phase II clinical study demonstrate the control of signs and symptoms and inflammation and safety profile of MRA in this disease. However, more studies need to be conducted before further conclusions can be drawn.”

About MRA
MRA is a humanized anti-IL-6 receptor monoclonal antibody whose novel mechanism of action may provide a new and effective form of treatment for adult RA. Phase II studies have been completed in Japan and Europe. Phase III clinical development in RA has been initiated in Japan and is under preparation in Europe and the USA. A Phase II study with MRA in systemic onset juvenile idiopathic arthritis (So-JIA) is also ongoing in Europe.

Roche and Chugai are developing MRA in collaboration with Osaka University. This co-development partnership was set up under the first licensing agreement between the two companies in 2003, where Roche will promote in all countries except Japan, South Korea and Taiwan, and the parties will co-promote in the UK, France and Germany. Other indications, such as Castleman’s disease, Crohn’s disease, juvenile idiopathic arthritis, and multiple myeloma, are also in clinical development.

About Rheumatoid Arthritis
RA is an autoimmune disorder of unknown cause, characterized by symmetric joint inflammation with erosive synovitis, and in some cases extra-articular involvement. Most patients experience a chronic fluctuating course of disease with joint swelling and pain that, despite therapy, may result in progressive joint destruction and ultimately lead to loss of function of joints. RA affects almost six million people around the world.

Roche Business Development and Alliance Strategy
Roche is a distinctive alliance partner with expertise in identifying cutting-edge innovation that can lead to new and improved medicines. During the past 18 months, Roche has formed over 45 new partnerships which span a wide range of therapeutic areas and technologies, making it an industry leader. Through its alliance strategy, Roche creates value with its partners by transforming these business transactions into productive relationships. A key element of Roche’s strategy is to enable its partners to achieve their vision while maintaining their cultural identity and entrepreneurial spirit.

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, 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 R&D agreements with numerous partners, including majority ownership interests in Genentech and Chugai.

About Chugai
Chugai Pharmaceutical Co., Ltd. is one of Japan’s leading research-based pharmaceutical companies with strengths in biotechnology products and in the therapeutic fields of oncology, renal diseases, cardiovascular diseases, bone/joint diseases and transplantation/infection/immunity. With pharmaceutical sales of 237 billion yen in 2002, Chugai has invested in research and development capabilities in the US and Europe, and has established sales and marketing operations in France, Germany and the UK. Chugai employs 5,867 employees worldwide.

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