Novel drug Actemra significantly improves the debilitating symptoms of Rheumatoid Arthritis in patients who have an inadequate response to standard therapy
Pivotal Phase III OPTION study published today in The Lancet
BASEL, Switzerland, 21 March 2008 - Patients with rheumatoid arthritis treated with ACTEMRA(tm) (tocilizumab) experienced a rapid and significant 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 major Phase III international study - demonstrated that rheumatoid arthritis (RA) patients not only achieved greater improvement of symptoms but also a higher quality-of-life with ACTEMRA, an innovative interleukin-6 (IL-6) receptor inhibitor, compared with methotrexate, a commonly used RA treatment.
"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 and stiffness, physical disability and fatigue despite treatment with existing therapies."
Rheumatoid arthritis is a progressive autoimmune disease characterized by inflammation of the membrane lining in the joints throughout the body. This inflammation causes distortion of the joint and impaired function accompanied by pain, stiffness and swelling and ultimately leading to irreversible joint destruction and disability. In addition, the systemic symptoms of RA include fatigue, anaemia, osteoporosis and may contribute to shortening life expectancy by affecting major organ systems. Sadly after 10 years, less than 50% of patients can continue to work or function normally on a daily basis.
ACTEMRA is the first humanized interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody and it represents a novel mechanism of action to treat RA. Research has shown that reducing the activity of IL-6, one of several key cytokines involved in the inflammatory process, reduces inflammation of the joints and relieves certain systemic effects of RA.
About the 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 metrotrexate patients. In the study, 43.9% of patients treated with ACTEMRA (8 mg/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 clinical remission (DAS28˜ 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 criteria3, compared with 35% for those treated with placebo and methotrexate at 24 weeks.
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.
ACTEMRA is the result of research collaboration by Chugai and is being co-developed globally with Chugai. ACTEMRA is the first humanized interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody. An extensive clinical development program of five Phase III trials was designed to evaluate clinical findings of ACTEMRA. Three other studies are completed and have reported meeting their primary endpoints. A fifth trial, a two-year study called LITHE (TociLIzumab safety and THE prevention of structural joint damage), is currently underway and is expected to report preliminary first-year data in 2008. ACTEMRA is awaiting approval in the United States and Europe. In Japan, ACTEMRA was launched by Chugai in June 2005 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.
ACTEMRA is generally well tolerated. The overall safety profile of ACTEMRA is consistent across all global clinical studies. The most common, non-serious, adverse events reported are upper respiratory tract infection, nasopharyngitis, headache and hypertension. As with other biological disease modifying anti-rheumatic drugs (DMARDs), serious infections and hypersensitivity reactions including a few cases of anaphylaxis, have been reported in some patients treated with ACTEMRA. Increases in liver transaminases (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.
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. 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.
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, and is a market leader in virology. It is also active in other major therapeutic areas such as autoimmune diseases, inflammatory and metabolic disorders and diseases of the central nervous system. In 2007 sales by the Pharmaceuticals Division totalled 36.8 billion Swiss francs, and the Diagnostics Division posted sales of 9.3 billion francs. Roche has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai, and invested over 8 billion Swiss francs in R&D in 2007. Worldwide, the Group employs about 79,000 people. Additional information is available on the Internet at www.roche.com.
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Notes to editors
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.
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Posted: March 2008