Roche today announced the results from two Phase III studies and one Phase II study that showed treatment with the investigational agent tocilizumab –marketed as ACTEMRA™ in Japan for Castleman’s Disease – consistently improved remission rates in patients with rheumatoid arthritis (RA) compared to placebo or other conventional antirheumatic treatments including the current standard of care methotrexate. The data were presented at the American College of Rheumatology annual meeting in Washington D.C.

In a one-year, 302-patient study, approximately 40% of the patients in the ACTEMRA group experienced a 70% improvement in certain symptoms and lab parameters (ACR70) at 52 weeks.  Approximately 59% of patients achieved DAS remission (<2.6). In two other studies, 70% improvement in symptoms was achieved in 28% of patients after 24 weeks, and 16% of patients after 12 weeks. The studies were part of a large RA clinical development program in Japan, involving nearly 600 patients, to evaluate the safety, efficacy and consistent response of ACTEMRA in the treatment of RA.

ACTEMRA is the first humanized interleukin-6 (IL-6) receptor-blocking monoclonal antibody to be studied as a potential 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 anemia, fatigue and osteoporosis. The ACTEMRA development program is designed to evaluate these questions.

“These findings are important because about half of all patients do not receive optimal results with current treatments, and these data suggest that targeted blockade of IL-6 shows promise in the treatment of RA,” said Mark C. Genovese, M.D., Associate Professor of Medicine at Stanford University School of Medicine.

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 Unites 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 Abstract
Data from three studies were analyzed and compared to determine patients’ response to treatment by using two standard assessments: ACR70, developed by the American College of Rheumatology (ACR), and DAS28, a measurement of RA disease activity. For example, 20%, 50% or 70% level of reduction (the percentage of reduction 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) is represented as ACR20, ACR50 and ACR70. An ACR70 response is considered exceptional for existing treatments and represents a significant improvement in a patient’s condition. The Disease Activity Score (DAS) is a combined index that measures disease activity (swollen and tender joints) in patients with RA. DAS28 <2.6 indicates significant improvement in RA disease activity.

Using the two standard measurements, researchers evaluated data across the following three studies:

• A Phase III study that involved 302 patients randomized to receive 8mg/kg of ACTEMRA compared to conventional DMARDs (disease modifying antirheumatic drugs) over a period of 52 weeks.
• A second Phase III trial with 125 patients who were randomized to receive 8mg/kg of ACTEMRA compared with methotrexate, the current standard of care, for a period of 24 weeks.
• A Phase II study that enrolled 163 patients who were randomized to receive either 4 or 8mg/kg of ACTEMRA or placebo for 12 weeks.

In the combined analysis, consistent disease remission was demonstrated in treatment with ACTEMRA compared to placebo and conventional DMARDs including methotrexate. In the 302-patient study, ACR20 was achieved in 89.2% of ACTEMRA-treated patients compared to 35.2% of patients receiving conventional therapy at 52 weeks; ACR70 was achieved in 43.3% of ACTEMRA-treated patients compared to 5.5% of patients receiving conventional therapy at 52 weeks; DAS28 was achieved in 58.6% of patients compared to 3.4% of patients, respectively.

In the second study, ACR20 was achieved in 80.3% of ACTEMRA-treated patients compared to 25.0% of patients receiving methotrexate at 24 weeks; ACR70 was achieved in 27.9% of ACTEMRA-treated patients versus 4.7% of patients receiving methotrexate at 24 weeks, and DAS28 was achieved in 41% of patients versus 1.6%.

In the third study with 163 patients, ACR20 was achieved in 78.2% of ACTEMRA-treated patients (8 mg/kg) compared to 11.3% of patients receiving placebo at 12 weeks; ACR70 was achieved in 16.4% of ACTEMRA-treated patients (8mg/kg) and DAS28 in 18.2% of patients at 12 weeks; no patients achieved ACR70 or DAS28 in the control group by week 12.

The most common adverse events reported in these studies were infections (primarily aggravated RA infections), anaphylactic reaction and hypersensitivity. Mild increases in liver function tests and lipid elevations were experienced; however most returned to near-baseline within 8 weeks of the last infusion of ACTEMRA.

About ACTEMRA (tocilizumab)
ACTEMRA (tocilizumab) is a humanized interleukin-6 (IL-6) receptor monoclonal antibody with a novel mechanism of action. It is an investigational agent which aims to become a new therapeutic option for the treatment of RA, a disease with a high unmet medical need.  Roche and Chugai have initiated a collaborative Phase III clinical development program in RA that is underway outside Japan with more than 4,000 patients expected to be enrolled in 41 countries including several European countries and the USA. The compound is not currently approved in the United States.

About Roche
Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S. pharmaceuticals headquarters of the Roche Group, one of the world’s leading research-oriented healthcare groups with core businesses in pharmaceuticals and diagnostics. For more than 100 years, the Roche Group has been committed to developing innovative products and services that address prevention, diagnosis and treatment of diseases, thus enhancing people's health and quality of life. An employer of choice, in 2005, Roche was named one of Fortune magazine’s Best Companies to Work For in America, one of the Top 20 Employers (Science magazine), ranked as the No. 3 Best Company to Work For in NJ (NJ Biz magazine), the No. 1 Company to Sell For (Selling Power), and one of AARP’s Top Companies for Older Workers. For additional information about the U.S. pharmaceuticals business, visit our websites: http://www.rocheusa.com or www.roche.us.