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Media Release

Basel, 27 October 2003

Phase II clinical study of MRA shows significant clinical benefit to children with systemic-onset Juvenile Idiopathic Arthritis
67th Annual Scientific Meeting of the American College of Rheumatology

F. Hoffmann-La Roche (Roche) and Chugai Pharmaceutical Co., Ltd. (Chugai) announced today new Phase II data which indicate that treatment with MRA provides significant clinical benefit to children suffering from systemic-onset juvenile idiopathic arthritis (So-JIA). 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 disease process of So-JIA.

This open, early Phase II dose-escalation clinical trial was designed to investigate the safety and efficacy of MRA in 11 children with active So-JIA. All the children were administered an initial intravenous dose of 2 mg/kg of MRA, followed by increased doses up to 8mg/kg depending on their levels of C-reactive protein (CRP), a marker of the disease activity.

MRA rapidly reduced the disease activity of So-JIA in 10 of 11 children. A 70% reduction of disease activity, as defined by a standard set of criteria, was achieved in 1 out of 3 children receiving 3 doses of 2mg/kg, in 3 out of 5 receiving 4mg/kg, and in all 3 children receiving 8mg/kg. The analysis of this data demonstrated a rapid improvement of clinical manifestations such as fever, rash, arthritis, and fatigue.

No children withdrew from the trial because of disease flare or adverse events.

These preliminary Phase II data show that MRA achieves a marked improvement of symptoms in children with active So-JIA and a normalization of acute phase reactants such as CRP as markers of inflammation. However, additional large-scale clinical trials 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 also 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. An early 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 was granted the right to promote in all countries except Japan, South Korea and Taiwan, and the parties would co-promote in the UK, France and Germany. Other indications, such as Castleman’s disease, Crohn’s disease, and multiple myeloma are also in clinical development.

About Juvenile Idiopathic Arthritis
Systemic-onset juvenile idiopathic arthritis (So-JIA) is a severe, steroid-dependent disorder, sometimes progressing to a fatal disease. Elevated serum IL-6 may play an important role in the clinical signs and symptoms of this disease. Approximately 20% of patients with juvenile rheumatoid arthritis suffer from So-JIA.

Roche Business Development and Alliance Strategy
Roche’s innovation strategy is based on strong in-house research with centres in Japan, Europe and the USA and strategic alliances with Genentech and Chugai. Complementing and strengthening the Group’s dynamic R&D capabilities are over 80 scientific and commercial collaborations with biotech companies and universities in clearly defined focus areas. In 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. A key element of this strategy is to enable its partners to achieve their vision while maintaining their cultural identity and entrepreneurial spirit.

About Roche
Headquartered in Basel, Switzerland, F. Hoffmann-La Roche (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, Roche contributes on a broad range of fronts to improving people’s health and quality of life. Roche employs roughly 62,000 people in 150 countries. Roche has alliances and research and development 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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