Investor Update

Basel, 25 July 2007

Actemra monotherapy demonstrates significant clinical benefit in patients with rheumatoid arthritis
AMBITION monotherapy study with novel interleukin-6 inhibitor meets primary endpoint of non-inferiority and shows superiority over methotrexate

Roche today announced that results from the AMBITION (Actemra versus Methotrexate double-Blind Investigative Trial In mONotherapy) trial, the fourth multinational Phase III study of ACTEMRA, not only successfully met its primary endpoint of non-inferiority in patients with moderate to severe rheumatoid arthritis (RA), but also demonstrated superiority over the standard effective dose regimen of methotrexate alone.

AMBITION is the first multinational Phase III study to examine ACTEMRA monotherapy against methotrexate in RA patients who have not been treated with methotrexate within 6 months and have not discontinued methotrexate at any time due to toxicity or lack of efficacy.  Results from this study – together with data from the three previous studies – will form the basis of the regulatory filing for marketing approval later this year.

“This is the first multinational phase III trial using Actemra monotherapy. The trial demonstrates Actemra’s safety and efficacy, reinforcing the role of IL-6 receptor inhibition in RA” said William M. Burns, CEO Pharmaceuticals Division of Roche. “These exciting data support Actemra’s potential as a new future therapy for RA patients.”

The trial showed that a significantly greater proportion of patients treated with ACTEMRA (8 mg/kg) achieved a significant reduction in the signs and symptoms of RA as evaluated by ACR20 following 24 weeks of treatment.   The study analysis included 673 patients from 252 trial sites in 18 countries, including the United States.   ACTEMRA was generally well tolerated; the most common adverse events reported more frequently in the ACTEMRA arm of the AMBITION trial were upper respiratory tract infections, headache and nasopharyngitis.

About the AMBITION Trial
The AMBITION trial is a two-arm, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of ACTEMRA (8 mg/kg) compared to methotrexate in RA patients. Patients received either ACTEMRA  intravenously every four weeks plus placebo capsules weekly or placebo infusions every four weeks plus methotrexate weekly.
Data from the study were analyzed to determine patients’ response to treatment by using three standard assessments: ACR score¹, developed by the American College of Rheumatology (ACR), as well as DAS², a measurement of RA disease activity, and EULAR response criteria³, a measurement of treatment response.

The AMBITION trial is one of five Phase III clinical studies designed to evaluate ACTEMRA  as a potential new treatment for RA. Three of the Phase III trials – OPTION, TOWARD and RADIATE – are completed and have reported meeting their primary study endpoints. At the European Congress of Rheumatology meeting in June, data results from the OPTION trial demonstrated that treatment with ACTEMRA plus methotrexate resulted in a significant improvement in RA symptoms in patients who had an inadequate response to methotrexate. An additional Phase III trial evaluating ACTEMRA in RA is ongoing; the two-year study – called LITHE – is expected to report one-year data in 2008.

About ACTEMRA (tocilizumab)
ACTEMRA is the first humanized interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody and represents a novel mechanism of action to treat RA. Studies suggest that reducing the
activity of IL-6, one of several key cytokines involved in the inflammatory process, may reduce
inflammation of the joints.  The ACTEMRA clinical development program is designed to evaluate this clinical finding. The most common adverse events reported in ACTEMRA global clinical studies have included upper respiratory tract infections, headache, nasopharyngitis and hypertension.  As with other biological disease modifying anti-rheumatic drugs (DMARDs), serious infections have been reported in some patients treated with ACTEMRA. The compound is not currently approved in the United States.  

About rheumatoid arthritis
Rheumatoid arthritis is a progressive, systemic autoimmune disease characterized by chronic inflammation of multiple joints and fatigue as well as the possibility of osteoporosis, anaemia, and lung, skin and liver effects. This inflammation causes pain, stiffness and swelling, resulting in loss of joint function due to destruction of the bone and cartilage, often leading to progressive disability. Further, as chronic inflammation continues, there may be shortening of life expectancy as a result of effects on major organ systems. After 10 years, less than 50% of patients can continue to work or function normally on a day to day basis. RA affects more than 21 million people worldwide.

About Roche in rheumatoid arthritis
One of the most important drivers for growth at Roche over the next few years is expected to be the company’s emerging franchise in autoimmune diseases with rheumatoid arthritis as the first indication. Following the launch of MabThera® (rituximab) there are a number of projects in development, potentially allowing Roche to build on further opportunities. MabThera is the first and only selective B-cell therapy for RA, providing a fundamentally different treatment approach by targeting B cells, one of the key players in the pathogenesis of RA. Actemra is Roche’s second novel medicine and is a humanised monoclonal antibody to the interleukin-6 (IL-6) receptor, inhibiting the activity of IL-6 , a protein that plays a major role in the RA inflammation process. Actemra is the result of research collaboration by Chugai and is being co-developed globally with Chugai. Additional projects creating a rich pipeline include compounds in Phase I, II and III clinical trials. Notably, ocrelizumab, a humanised anti-CD20 antibody, has entered phase III development for RA.

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 the world’s biggest biotech company and an innovator of products and services for the early detection, prevention, diagnosis and treatment of diseases, the Group contributes on a broad range of fronts to improving people’s health and quality of life. Roche is the world leader in in-vitro diagnostics and drugs for cancer and transplantation, a market leader in virology and active in other major therapeutic areas such as autoimmune diseases, inflammation, metabolism and central nervous system. In 2006 sales by the Pharmaceuticals Division totalled 33.3 billion Swiss francs, and the Diagnostics Division posted sales of 8.7 billion Swiss francs. Roche employs approximately 75,000 worldwide 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 at www.roche.com.

Further information
- Roche & Autoimmune diseases

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1) ACR20, ACR50 and ACR70 represent the percentage of reduction (20%, 50% or 70%) in certain RA symptoms and measures like the number of tender and swollen joints, pain, patient’s and physician’s global assessments and certain laboratory markers. An ACR70 response is considered exceptional and represents a significant improvement in a patient’s condition.
2) The Disease Activity Score (DAS) is a clinical index that measures RA disease activity and combines information from swollen and tender joints, acute phase response and general health into one measurement. The level of disease activity is interpreted as low (DAS <2.4), moderate (2.4 < DAS < 3.7, or high (DAS > 3.7). DAS < 1.6 corresponds to being in remission according to the criteria of the American Rheumatism Association (ARA).  
3) The EULAR response criteria is based on the individual amount of change in DAS and the DAS value (low, moderate, high disease activity) reached to classify patients as good, moderate and non-responders.