Roche's ACTEMRA Significantly Improves Symptoms of Rheumatoid Arthritis

Results of the OPTION (TOcilizumab Pivotal Trial in Methotrexate Inadequate respONders) trial, the first multinational Phase III study outside of Japan, showed that patients treated with ACTEMRA(TM) (either 4mg/kg or 8mg/kg) plus methotrexate achieved a significant and clinically important improvement in the signs and symptoms of moderate to severe rheumatoid arthritis (RA) compared to patients treated with placebo and methotrexate, a current standard of care. The data were presented today at the European Congress of Rheumatology (ECR) held by the European League Against Rheumatism (EULAR) in Barcelona, Spain.

In the 623-patient study, 58.5% of patients receiving the combination of ACTEMRA(TM) (8mg/kg) and methotrexate achieved at least a 20% improvement (ACR20) in RA symptoms compared with 26.5% of patients receiving placebo plus methotrexate after 24 weeks. The data also showed that 79.5% of patients in the ACTEMRA(TM) (8mg/kg) plus methotrexate group responded with moderate to good improvements in RA symptoms (EULAR response) compared to 34.8% for those treated with placebo and methotrexate at 24 weeks. ACTEMRA(TM) was generally well tolerated; the most common adverse events reported more frequently in the ACTEMRA(TM) arms of the OPTION trial were upper respiratory tract infection, nasopharyngitis and headache.

Other parameters measured in the study included C-reactive protein (CRP), a marker of inflammation, fatigue and hemoglobin. Patients in the ACTEMRA(TM) 8 mg/kg group showed a rapid lowering of CRP levels within two weeks, while fatigue scores showed that patients in the ACTEMRA(TM) group experienced a reduction in fatigue and a rapid improvement in hemoglobin levels. Low levels of hemoglobin are usually associated with anemia (reduction in red blood cells) that can result in tiredness and fatigue.

"There is a critical need for new therapies to treat moderate to severe RA patients, and these results suggest that IL-6 inhibition is an encouraging anti-inflammatory mechanism for reducing disease symptoms," said Mark C. Genovese, M.D., Associate Professor of Medicine at Stanford University School of Medicine.

ACTEMRA(TM) is the first humanized interleukin-6 (IL-6) receptor- inhibiting monoclonal antibody and represents a novel mechanism of action for the treatment for 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, prevent long-term damage and relieve certain systemic effects of RA such as decreased hemoglobin, fatigue and osteoporosis.

"These study results underscore the potential for ACTEMRA(TM) to become a new treatment option for RA," said Lars Birgerson, M.D., Ph.D., Vice President, Global Head Medical Affairs, Roche. "We are hopeful that the ongoing Phase III trials will translate into improved clinical outcomes for patients."

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. RA affects more than 21 million people worldwide with approximately 2.5 million people affected in the United States. RA may also 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 the Study

The OPTION trial is a three-arm, randomized, double-blind, controlled Phase III study designed to evaluate the safety and efficacy of ACTEMRA(TM) plus methotrexate compared to placebo plus methotrexate in patients with moderate to severe RA who had an inadequate response to methotrexate alone. Patients received ACTEMRA(TM) intravenously (either 4mg/kg or 8mg/kg) every 4 weeks plus methotrexate weekly, or placebo infusions plus methotrexate weekly, for 24 weeks. The study enrolled patients at 73 trial sites in 17 countries outside the United States, and is one of five Phase III trials designed to study ACTEMRA(TM) as a potential new treatment for RA.

Data from the study were analyzed to determine patients' response to treatment by using three standard assessments: ACR score(1), developed by the American College of Rheumatology (ACR), DAS28(2), a measurement of RA disease activity, and EULAR(3), a measurement of treatment response.

In the study, 43.9% of patients treated with ACTEMRA(TM) (8mg/kg) plus methotrexate achieved at least a 50% (ACR50) reduction in symptoms compared to 10.8% of patients receiving placebo and methotrexate; ACR70 was achieved in 22% of the treatment group versus 2% in the control group. At 24 weeks, disease remission, as measured by DAS28 (5.1). DAS28