Basel, 11 July 2006

MabThera approved for use in rheumatoid arthritis in Europe

Unique mode of action brings new treatment option to rheumatoid arthritis suffers with an inadequate response to current biologic therapies

Roche announced today that MabThera (rituximab) has been approved by the European Commission for the treatment of rheumatoid arthritis (RA) in Europe. MabThera in combination with methotrexate is indicated for the treatment of adult patients with severe active rheumatoid arthritis who have had an inadequate response or are intolerant to current treatment options including one or more tumour necrosis factor (TNF) inhibitors. MabThera is the first and only selective B cell therapy for RA offering a fundamentally different treatment approach.
B cells play a key role in driving the RA disease process and MabThera is thought to break this process so preventing disease effects and leading to lasting benefits for the patient.

The approval of MabThera is based on the impressive results of the REFLEX¹ trial where MabThera in combination with methotrexate, was shown to be a highly effective therapy for controlling symptoms and improving the physical and mental health of patients with RA. FDA approval was received in the US earlier this year.

RA is one of the most common forms of autoimmune disease which affects more than 21 million people worldwide, with as many as 3 million sufferers in Europe alone. Currently up to 40 per cent of people with RA who are treated with biologic therapies such as TNF inhibitors, do not have satisfactory outcomes.

“Due to the high number of patients who do not respond or tolerate currently available therapies, there is a great need for novel and effective options”, said William M. Burns, CEO of Roche’s Pharmaceutical Division. “We are confident that MabThera, Roche’s first innovative treatment for RA, will bring relief to patients with this debilitating disease and that our ongoing research and development programmes will yield more therapies for those who need them.”

About the REFLEX study
The REFLEX study is a multi-centre, randomized, double-blind, placebo-controlled Phase III study. In this trial, patients who received an initial course of only two infusions of 1000mg of MabThera two weeks apart, with a stable dose of methotrexate displayed a statistically significant improvement in symptoms (ACR²) measured at 24 weeks, compared to those receiving placebo and methotrexate. Consistent with previous findings, analysis of the REFLEX 24-week data did not reveal any unexpected safety signals. Roche continue to monitor the long-term safety of MabThera in all clinical trials.

One year data presented recently at a major European congress (EULAR) showed that MabThera significantly inhibits the structural damage to joints caused by RA in patients who have had an inadequate response to TNF inhibitor therapies. To date no other RA therapy has shown evidence of inhibition of joint structural damage in this patient group. In addition, the question around subsequent treatment courses was answered as patients receiving additional courses did so between 6 and 12 months after the initial course and experienced further improvement of symptoms. Furthermore, remission rates doubled from a DAS28³ remission rate of 6% following an initial course to 13% following a second course of MabThera treatment.

A comprehensive Phase III clinical development programme is currently underway to further investigate the potential clinical benefit of MabThera in earlier RA.

About rheumatoid arthritis
Rheumatoid arthritis is a progressive, systemic autoimmune disease characterized by inflammation of the membrane lining in joints. This inflammation causes a loss of joint shape and function, resulting in pain, stiffness and swelling, ultimately leading to irreversible joint destruction and disability. Characteristics of RA include swelling, pain, and movement limitation around joints of the hands, feet, elbows, knees and neck. RA may shorten life expectancy by affecting major organ systems and after 10 years, less than 50% of patients can continue to work or function normally on a day to day basis.

About MabThera in rheumatoid arthritis
MabThera selectively targets a subset of B cells that express CD20, leaving stem, pro-B and plasma cells unaffected. The B cells play a key role in the autoimmune process of RA and MabThera aims to interrupt this process by inhibiting a series of reactions inflaming the synovia and leading to cartilage loss and bone erosion that is characteristic of the disease . More than 1000 patients with RA have been treated with MabThera in clinical trials to date.

MabThera is well established in the treatment of a form of lymphatic cancer called non-Hodgkin’s lymphoma (NHL) where over 730,000 patients have been treated with MabThera over a seven year period without major safety concerns

MabThera is marketed in the US by Genentech and Biogen Idec under the brand name Rituxan.

About Roche
Headquartered in Basel, Switzerland, Roche is one of the world’s leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As a supplier of innovative products and services for the early detection, 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 is a world leader in diagnostics, the leading supplier of medicines for cancer and transplantation and a market leader in virology. In 2005 sales by the Pharmaceuticals Division totalled 27.3 billion Swiss francs, and the Diagnostics Division posted sales of 8.2 billion Swiss francs. Roche employs roughly 70,000 people in 150 countries and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai. Additional information about the Roche Group is available on the Internet (www.roche.com).

All trademarks used or mentioned in this release are legally protected.


For further information
- British Society for Rheumatology
- American College of Rheumatology
- About Genentech
- About BiogenIdec


References:
1The REFLEX study (Randomised Evaluation oF Long-term Efficacy of Rituximab in RA) is a multi-centre, randomized, double-blind, placebo-controlled Phase III study.
2The ACR response is a standard assessment used to measure patients’ responses to anti-rheumatic therapies, devised by the American College of Rheumatology (ACR). It requires a patient to have a defined percentage reduction in a number of symptoms and measures of their disease. For example, a 20 or 50% level of reduction (the percentage of reduction of RA symptoms) is represented as ACR20, ACR50 or ACR70. An ACR70 response is exceptional for existing treatments and represents a significant improvement in a patient’s condition.
3The DAS28 score reflects improvements in inflammatory disease activity in RA. The DAS28 represents a composite index of disease activity and is calculated by combining scores for swelling and tenderness in 28 joints with physician and patient global assessments of disease activity and C-reactive protein (CRP) level. Remission is defined as a DAS28 score of less than 2.6 and is considered to be a point at which a patient experiences no symptoms of disease.