Roche Holding Arthritis Drug Effective in Late-Stage Trial
NUTLEY, N.J., Nov. 7 -- Data from two pivotal multinational Phase III clinical trials demonstrating that Roche's ACTEMRA(TM) (tocilizumab) significantly improved the signs and symptoms of rheumatoid arthritis (RA) patients who failed to adequately respond to anti-rheumatic therapies -- also known as disease modifying agents (DMARDs) -- will be highlighted at the American College of Rheumatology (ACR) Annual Scientific Meeting in Boston, November 6-11.
Late-breaking data results from the TOWARD (Tocilizumab in cOmbination With traditional DMARD therapy) trial and OPTION (TOcilizumab Pivotal Trial in Methotrexate Inadequate respONders) trial will both be featured in oral presentations. Additionally, study results of the OPTION trial will be featured at an ACR press conference on Saturday, November 10 at 8:30 a.m.
"We are very encouraged by the findings of this new TOWARD data which suggest 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. "The data from both studies further establish the efficacy of ACTEMRA and confirm that inhibiting interleukin-6 (IL-6) receptor is a novel method of reducing RA symptoms."
In the TOWARD trial, 61% of patients in the ACTEMRA plus DMARDs arm achieved a 20% reduction in RA symptoms compared with 25% of patients in the placebo arm (p<0.0001) at 24 weeks. Within two weeks there was a measurably higher ACR20 response with ACTEMRA than the control arm. In the OPTION trial, 59% of patients in the ACTEMRA 8 mg/kg plus methotrexate arm experienced a 20% reduction in symptoms versus 27% of patients in the placebo arm (p<0.0001) at 24 weeks. Data from the two studies showed that more than half of patients experienced at least a 20% reduction in RA symptoms (ACR20) in the ACTEMRA plus DMARD therapies groups compared to the placebo plus DMARD therapies groups. 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.
"It is vital that physicians have a variety of treatment options to offer patients to treat this debilitating and chronic disease," said Josef Smolen, M.D., lead investigator of the OPTION trial and Professor of Medicine at the University Clinic for Internal Medicine in Vienna, Austria. "ACTEMRA may offer a novel approach to help patients who may not be achieving sufficient relief from standard therapies like methotrexate."
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 study treated 1,216 patients at 130 trial sites in 18 countries, including the United States.
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.
Study Results
Both TOWARD and OPTION studies showed that at 24 weeks significantly more patients achieved a 20%, 50% and 70% (ACR20, ACR50 and ACR70) reduction of symptoms with ACTEMRA plus DMARD therapies compared to the control group. In the TOWARD trial, 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. In the OPTION trial, 59%, 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 placebo plus methotrexate control arm.
"We are excited to announce these results as they indicate that ACTEMRA and its unique IL-6 inhibition may become a significant new treatment option for people suffering from RA," said Lars Birgerson, M.D., Ph.D, Vice President, Global Head Medical Affairs, Roche. "Findings from these studies will be part of the application to the U.S. Food and Drug Administration that we intend to submit by year's end."
In the TOWARD trial, disease remission was demonstrated in 30% of ACTEMRA patients (DAS28 <2.6) compared with 3.4% of patients treated with only DMARDs. In the OPTION trial disease remission was demonstrated in 28% of ACTEMRA patients (DAS28 <2.6) compared with 1% of patients treated with methotrexate alone. In both studies, levels of C-reactive protein (CRP), a marker of inflammation, and hemoglobin levels, showed an improvement within two weeks and remained at normal levels through the end of both studies. According to both studies, patients treated with ACTEMRA plus anti-rheumatic therapies experienced greater improvements in quality of life and function measures, including fatigue, physical and mental functions compared to placebo plus anti-rheumatic treatments.
Other Studies
The TOWARD and OPTION trials are part of a large clinical development program that enrolled more than 4,000 RA patients in 41 countries, including the United States and several European countries. Two others, RADIATE (Research on ACTEMRA Determining effIcacy after Anti-TNF FailureEs) and AMBITION (ACTEMRA versus Methotrexate double-Blind Investigative Trial In MONotherapy) are completed and have reported meeting their primary study endpoints as well. An additional Phase III trial is ongoing; this two-year study, called LITHE (TociLIzumab safety and THE prevention of structural joint damage), is expected to report one-year data later in 2008.
About ACTEMRA (tocilizumab)
ACTEMRA is the first humanized interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody and represents a novel mechanism of action to treat 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 structural damage and relieve certain systemic effects of RA such as decreased hemoglobin, fatigue and osteoporosis. The ACTEMRA clinical development program is designed to evaluate these clinical findings. The compound is not currently approved in the United States. 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.
The most common adverse events reported in ACTEMRA global clinical studies are 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.
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 and 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 2.1 million people affected 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 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 and one of the Top 20 Employers (Science magazine). In 2006, Roche was ranked the No. 1 Company to Sell For (Selling Power), and one of AARP's Top Companies for Older Workers, and in 2005, Roche was named one of Fortune magazine's Best Companies to Work For in America. For additional information about the U.S. pharmaceuticals business, visit our websites: http://www.rocheusa.com or www.roche.us.
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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 (range0-28), erythrocyte sedimentation rate, and a general health assessment on a visual analog scale. The level of disease activity is interpreted as low (DAS28 less than or equal to 3.2), moderate (3.2 less than DAS28 less than or equal to 5.1) or high (DAS28 greater than 5.1). DAS28 less than 2.6 corresponds to being in remission according to the criteria of the American College of Rheumatology.