Healthcare Industry News: Methotrexate
News Release - March 20, 2008
International ACTEMRA Rheumatoid Arthritis Study Highlighted in The LancetBy targeting interleukin-6 receptors, ACTEMRA provides significant benefits for patients when compared with existing therapies
NUTLEY, N.J., March 20 (HSMN NewsFeed) -- Patients with rheumatoid arthritis treated with Roche's ACTEMRA(TM) (tocilizumab) experienced significant and rapid reduction in the signs and symptoms of their disease, according to a study published in this week's issue of The Lancet. Results from the OPTION (TOcilizumab Pivotal Trial in Methotrexate Inadequate respONders) trial -- a Phase III international study -- demonstrated that RA patients achieved greater improvement of symptoms and a higher quality-of-life with ACTEMRA, an interleukin-6 (IL-6) receptor inhibitor, in combination with Methotrexate, compared with Methotrexate plus placebo.
"Results of this pivotal study convincingly demonstrate that tocilizumab can effectively and rapidly diminish the painful and debilitating effects of rheumatoid arthritis," said Josef Smolen, M.D., lead investigator of the OPTION trial and Professor of Medicine at the Department of Internal Medicine at the Medical University of Vienna, Austria. "These trial findings are significant because we know that many rheumatoid arthritis patients continue to experience symptoms of joint pain, stiffness, physical disability and fatigue, despite treatment with existing therapies."
About OPTION Study
In the OPTION trial, a three-arm, double-blind, controlled Phase III study, 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. The study was conducted in 73 trial sites in 17 countries outside the United States.
At 24 weeks, 58.5% of ACTEMRA patients (8mg/kg) achieved a 20% reduction in RA symptoms (ACR20)(1), compared with 26.5% of patients in placebo plus Methotrexate patients. In the study, 43.9% of patients treated with ACTEMRA (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. A rapid decrease in disease activity (DAS28)(2) was seen as early as two weeks in a greater proportion of patients treated with ACTEMRA plus Methotrexate, with 27.5% achieving DAS28 less than or equal to 2.6 by 24 weeks.
Additionally, results showed that 80% of patients in the ACTEMRA (8mg/kg) plus Methotrexate group responded with moderate to good improvements in RA symptoms, according to the EULAR response criteria(3), compared with 35% for those treated with placebo and Methotrexate at 24 weeks. ACTEMRA was generally well tolerated; the most common adverse events reported more frequently in the ACTEMRA arms of the OPTION trial were upper respiratory tract infection, nasopharyngitis and headache.
The OPTION trial also assessed physical function and quality-of-life at baseline and every four weeks thereafter. Patients receiving ACTEMRA achieved significantly greater improvement in areas of fatigue and mental function at 24 weeks, and achieved normal levels of hemoglobin and C-reactive protein (CRP), a marker of inflammation due to RA, compared with patients receiving placebo plus Methotrexate.
"We are very encouraged by the findings of the study as they further establish the role of ACTEMRA and its unique blockade of IL-6 receptors as a potential new biologic treatment option for patients with RA," said Lars Birgerson, M.D., Ph.D, Vice President, Global Head Medical Affairs, Roche.
About ACTEMRA(TM) (tocilizumab)
ACTEMRA is the first humanized interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody. 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 and relieve certain systemic effects of RA. The extensive clinical development program conducted by Roche includes five clinical studies and has enrolled more than 4,000 patients in 40 countries, including the United States. Three of these studies are completed and have reported meeting their primary endpoints. Another Phase III trial evaluating ACTEMRA in RA is an ongoing two-year study and is expected to report one-year data evaluating the effect of ACTEMRA on the inhibition of structural joint damage later this year. ACTEMRA is awaiting approval in the United States and Europe.
ACTEMRA is part of a co-development agreement with Chugai, a Japanese company. In June 2005, ACTEMRA was launched by Chugai in Japan as a therapy for Castleman's disease; in April 2006, additional indications for rheumatoid arthritis and systemic-onset juvenile idiopathic arthritis were also filed in Japan and are currently under review.
The serious adverse events reported in ACTEMRA clinical trials were serious infections and hypersensitivity reactions including anaphylaxis. The most common adverse events reported in clinical studies were upper respiratory tract infection, nasopharyngitis, headache and hypertension. Increases in liver function tests (ALT and AST) were seen in some patients; these increases were generally mild and reversible, with no hepatic injuries or any observed impact on liver function.
IL-6 is a common protein found in all joints in the body and is a natural substance that can raise inflammation. Everyone has IL-6 in their body, but people with RA may have too much. If approved, ACTEMRA will be the first and only medication to specifically target IL-6 in patients with RA.
About Rheumatoid Arthritis
Rheumatoid arthritis is a progressive, systemic autoimmune disease characterized by inflammation of the membrane lining in the 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 redness, swelling, pain and movement limitation around joints of the hands, feet, elbows, knees and neck that leads to loss of function. In addition, the systemic symptoms of RA include fatigue, decreased hemoglobin, osteoporosis and may contribute to shortening life expectancy by affecting major organ systems. After 10 years, less than 50% of patients can continue to work or function normally on a daily basis. RA affects more than 21 million people worldwide with approximately 1.3 million adults affected in the United States.
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 in the U.S., Roche 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 2007 Roche was named Top Company of the Year by Med Ad News, one of the Top 20 Employers (Science) and ranked the No. 1 Company to Sell For (Selling Power). In previous years, Roche has been named as a Top Company for Older Workers (AARP) and one of the Best Companies to Work For in America (Fortune). For additional information about the U.S. pharmaceuticals business, visit our websites: http://www.rocheusa.com or www.roche.us.com
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(1) ACR20, ACR50, ACR70 represent the percentage of reduction (20%, 50%, 70%) in certain RA symptoms and measures that number of tender and swollen joints, pain, patient's and physician's global assessments and certain laboratory markers.
(2) The Disease Activity Score (DAS)28 is a combined index that measures disease activity in patients with RA. It combines information from 28 tender and swollen joints (range 0-28), erythrocyte sedimentation rate, and a general health assessment on a visual analog scale. The level of disease activity is interpreted as low (DAS28 < 3.2), moderate (3.2 < DAS28 < 5.1) or high (DAS28 >5.1). DAS28 <2.6 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.
Source: Roche Group
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