New Actemra Data Shows Significant Benefit for Patients Suffering From Rheumatoid Arthritis

TOWARD study, presented at major US congress ACR, confirms IL-6 receptor inhibition plays a key role in the treatment of RA

BASEL, Switzerland, 7th November 2007 The innovative new rheumatoid arthritis drug Actemra (tocilizumab) has been shown to significantly improve the signs and symptoms of rheumatoid arthritis (RA) in patients who failed to achieve an adequate response to traditional disease modifying agents (DMARDs). Exciting new data from the TOWARD1 study, being presented as a late breaker, at the American College of Rheumatology (ACR) Annual Scientific Meeting in Boston, November 6-11, reinforce the benefit of tackling RA through the inhibition of the IL-6 pathway.

In the TOWARD trial, 61% of patients in the Actemra plus DMARD group achieved a 20% reduction in RA symptoms (ACR202 response) compared with only 25% of patients in the control group. Around one in three patients achieved clinical remission in the Actemra group, as assessed using DAS28 <2.63 .These results are consistent with the results of another Actemra trial, the OPTION4 study, which were previously reported and which will be the subject of further presentations at ACR. The OPTION study showed that 59% of patients in the Actemra treatment arm experienced a 20% reduction in RA symptoms (ACR 20 response) versus only 27% of patients in the control group.

"We are very encouraged by the findings of this new TOWARD data which suggest that Actemra plus DMARDs demonstrates significant improvement in RA symptoms compared with DMARDs alone," said Mark C. Genovese, M.D., lead study investigator of the TOWARD trial and associate Professor of Medicine at Stanford University School of Medicine. "These data further establish the efficacy of Actemra and confirm that inhibiting the interleukin-6 (IL-6) receptor is a novel method of reducing RA symptoms."

"These results show that remission rates achieved with Actemra compare favourably with current RA therapies indicating the medicine's potential to become a very effective new treatment option," said Dr. Urs Schleuniger, Head of Inflammatory Diseases, Roche. "Findings from the TOWARD and OPTION studies will be part of the application to Regulatory Authorities that we intend to submit by the end of the year."

About TOWARD Study

The TOWARD trial, a two-arm, double-blind, placebo-controlled study was designed to evaluate the safety and efficacy of Actemra plus DMARDs compared to placebo plus DMARDs in RA patients. Patients were randomized to receive either Actemra intravenously (8mg/kg) every four weeks plus DMARDs weekly or placebo infusions plus DMARDs weekly. The multicentre study treated 1,216 patients at 130 trial sites in 18 countries, including the U.S.

At 24 weeks significantly more patients achieved a 20%, 50% and 70% (ACR20, ACR50 and ACR70) reduction of symptoms with Actemra plus DMARDs compared to the control group. The ACR20, ACR50 and ACR70 was achieved in 61%, 38% and 21%, respectively, of Actemra plus DMARDs patients versus 25%, 9% and 3%, respectively, in the placebo plus DMARDs arm. Disease remission was demonstrated in 30% of Actemra patients (DAS28 <2.6) compared with 3 % of patients treated with only DMARDs.

About OPTION Study

In the OPTION trial, 623 patients were randomized to receive Actemra intravenously (either 4mg/kg or 8mg/kg) every four weeks plus methotrexate weekly or placebo infusions plus methotrexate weekly. OPTION, a three-arm, double-blind, controlled study, evaluated the safety and efficacy of Actemra plus methotrexate compared to placebo plus methotrexate in RA patients. The study was conducted in 73 trial sites in 17 countries, outside the United States. At 24 weeks significantly more patients achieved a 20%, 50% and 70% (ACR20, ACR50 and ACR70) reduction of symptoms with Actemra plus methotrexate compared to the control arm. Fifty nine per cent, 44% and 22%, respectively, of patients treated with Actemra (8mg/kg) plus methotrexate achieved ACR20, ACR50 and ACR70 compared with 27%, 11% and 2%, respectively, in the control group. Disease remission was demonstrated in 28% of Actemra patients (DAS28 <2.6) compared with 1 % of patients treated with methotrexate alone.

Other parameters measured in both studies, included levels of C-reactive protein (CRP), a marker of inflammation, fatigue and haemoglobin. Patients on Actemra showed a rapid normalisation of the CPR levels within two weeks and a rapid improvement in haemoglobin levels. According to both studies, patients treated with Actemra plus DMARDs experienced greater improvements in quality of life and function measures, including fatigue and physical and mental functions compared to placebo plus DMARDs.

Actemra generally well tolerated in both TOWARD and OPTION

Actemra was generally well tolerated in both studies. The most common adverse events reported more frequently in the Actemra arm were upper respiratory tract infections, headache, nasopharyngitis and hypertension. As with other disease modifying

anti-rheumatic drugs, serious infections have been reported in some patients treated with Actemra.

Other studies The TOWARD1 and OPTION2 trials are two of five phase III clinical studies designed to evaluate Actemra as a potential new treatment for RA. Two others, RADIATE5 and AMBITION6- are completed and have met their primary study endpoints. An additional phase III trial is ongoing; the two-year study, called LITHE7, and this study is expected to report data later in 2008.All studies are expected to be presented at upcoming medical meetings in 2008.

About Actemra

Actemra is the first humanised interleukin-6 (IL-6) receptor inhibiting monoclonal antibody and represents a novel mechanism of action to treat RA, a disease with a high unmet medical need. The overall safety profile observed in the global studies of Actemra is consistent and Actemra is generally well tolerated. The most frequent adverse events reported 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. Roche and Chugai are collaborating on a phase III clinical development programme in RA running outside Japan, with more than 4000 patients enrolled in 41 countries including several European countries and the USA. In Japan, Actemra was launched in June 2005 as a therapy for Castleman's disease and in April 2006 filed for the additional indications of rheumatoid arthritis and systemic-onset juvenile idiopathic arthritis.

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, metabolic disorders and diseases of the 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 has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai, and invests approximately 7 billion Swiss francs a year in R&D. Worldwide, the Group employs about 75,000 people. Additional information is available on the Internet at www.roche.com. Additional information about the Roche Group is available on the Internet at www.roche.com.

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Posted: November 2007

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