Basel, 2 June 2006

MabThera recommended for approval in rheumatoid arthritis in Europe

First selective B cell therapy provides patients with a real option to tackle this debilitating disease

Roche announced today that MabThera (rituximab) has received a recommendation for approval from the Committee for Medicinal Products for Human Use (CHMP) for the treatment of rheumatoid arthritis (RA) in Europe. MabThera is now a step closer to being available for RA patients who have had an inadequate response or intolerance to current treatment options (including TNF inhibitors) and is the first and only selective B cell therapy. B cells play a key role in the chain of inflammatory events that ultimately lead to the damage of bone and cartilage in the joints, both serious outcomes characteristic of RA.

Professor Paul Emery, University of Leeds, UK, one of the lead investigators in the REFLEX1 study commented: “This is a very exciting time – MabThera is set to make a substantial difference to people suffering from RA in Europe who do not receive sufficient relief from currently available therapy or who are not able to tolerate it. This new approach has the ability to provide long lasting clinical benefits with each short course of therapy every six to twelve months.”

“This positive opinion is a major milestone for MabThera - the first treatment for RA in our autoimmune portfolio. We are delighted that MabThera will soon be available as a new therapeutic option for many people afflicted with this debilitating disease” said Eduard Holdener, Head of Roche’s Global Pharma Development.

As per the CHMP positive opinion, 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 intolerance to other disease-modifying anti-rheumatic drugs including one or more tumour necrosis factor (TNF) inhibitors. Of the RA patients treated with current biologic therapy, up to 40% do not have a satisfactory outcome and at present have few treatment alternatives. There is therefore a high need for novel and effective options for patients whose daily life continues to be impacted by this serious disease.

The announcement from the CHMP follows positive results from the phase III REFLEX study which showed that MabThera is a highly effective therapy for controlling symptoms in RA patients, providing lasting improvement after only two infusions per treatment course. The study showed that in particular, MabThera shows impressive results in reducing swollen and tender joints, improving fatigue and the quality of life of patients. Further analysis of the REFLEX trial including one year radiographic data and the effect of repeat treatment courses, will be presented at the European League Against Rheumatism (EULAR) in June 2006.

MabThera, marketed in the US by Genentech under the brand name Rituxan, has recently also received FDA approval for treatment of moderate to severe RA, after priority review.

RA is one of the most common forms of autoimmune disease which affects more than 21 million people worldwide, with up to 2 million sufferers in Europe alone.

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.

About the REFLEX study
The REFLEX study (Randomised Evaluation oF Long-term Efficacy of Rituximab in RA) is a multi-centre, randomized, double-blind, placebo-controlled Phase III study. In this trial, patients who received a single course of only two infusions of MabThera with a stable dose of methotrexate (MTX) displayed a statistically significant improvement in symptoms measured at 24 weeks, compared to those receiving placebo and MTX. Most of the patients who received additional courses did so 24 weeks after the previous course. A preliminary analysis of the REFLEX data did not reveal any unexpected safety signals and the companies continue to monitor the long-term safety of MabThera in all clinical trials.

Significant improvements across all symptom parameters
The results of the six-month analysis show that MabThera in combination with methotrexate (MTX), a standard RA treatment, was highly effective, producing statistically significantly higher response rates compared to MTX plus placebo: 51% of patients achieved 20% improvement in signs and symptoms (ACR202 ), compared to 18% with MTX alone. The difference in the two groups was apparent after 8 weeks and sustained for the duration of the study after only one course of 2 infusions of MabThera, two weeks apart. Over the six-month period, more than five times as many patients in the MabThera group achieved a 50% improvement in signs and symptoms compared to MTX alone (ACR50: 27% vs 5%), and twelve times more MabThera patients achieved a 70% improvement (ACR70: 12% vs 1%). Most patients who received additional courses did so 6 months after the previous course.

About MabThera in rheumatoid arthritis
MabThera selectively targets a subset of B cells that express CD20, leaving stem, pro-B and plasma cells unaffected. This subset of B cells plays 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. A comprehensive phase III clinical development programme is also 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 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).

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References:
1  The REFLEX study (Randomised Evaluation oF Long-term Efficacy of Rituximab in RA) is a multi-centre, randomized, double-blind, placebo-controlled Phase III study.
2  The 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.