- Fifth International Phase III ACTEMRA Study Meets its Primary Endpoints -
NUTLEY, N.J., May 25 /PRNewswire/ -- Roche today announced that two-year data from the LITHE (TociLIzumab Safety and THE Prevention of Structural Joint Damage) study demonstrated that ACTEMRA(R) (tocilizumab) continued to inhibit the progression of structural damage to joints in patients with rheumatoid arthritis (RA). The study also showed that patients receiving ACTEMRA experienced improved physical function, as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI) scores(1). The LITHE study is the fifth international Phase III study in the extensive ACTEMRA clinical development program to successfully meet its primary endpoints in patients with moderately to severely active RA.
"The one-year LITHE results demonstrated that ACTEMRA significantly inhibited the progression of structural joint damage, which is a major cause of disability and loss of physical function for RA patients," said Kenneth Bahrt, M.D., Global Medical Director, Autoimmunity, Roche. "We are extremely pleased by these two-year LITHE data as they confirm the previous study findings, and also suggest that the effect of ACTEMRA actually improves over time."
The two-year data from the LITHE study showed that patients treated with ACTEMRA maintained consistently high disease remission rates according to DAS28 criteria, which measures disease activity in RA patients(2). The study also showed that a greater proportion of patients treated with ACTEMRA (8 mg/kg and 4 mg/kg) plus methotrexate achieved a significant reduction in the progression of structural joint damage during 24 months of treatment compared with patients receiving placebo plus methotrexate. The outcome was determined by X-ray evidence of the progression of bone erosion and narrowing of joint spaces, as measured by the Genant-modified Sharp score(3).
In the study, ACTEMRA was generally well-tolerated and the overall safety profile after two years of treatment with ACTEMRA was consistent with previously reported data. Full data from this two-year study will be submitted to the U.S. Food and Drug Administration (FDA) and for presentation at a future international scientific meeting.
One-year LITHE data have been accepted for presentation at the 10th Annual Congress of the European League Against Rheumatism (EULAR), which will take place June 10-13, 2009, in Copenhagen, Denmark.
About the LITHE Study
The LITHE study was a three-arm, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of ACTEMRA (8 mg/kg and 4 mg/kg) plus methotrexate compared with placebo plus methotrexate in RA patients. Patients in the LITHE study received either ACTEMRA intravenously every four weeks plus methotrexate weekly or placebo infusions every four weeks plus methotrexate weekly. The LITHE study included nearly 1,200 patients from 137 sites in 15 countries, including the United States. The study aimed to show the inhibition of structural damage at the joints, as demonstrated by changes in validated radiographic parameters. The study also examined the improvement in physical function and disease signs and symptoms.
One-year data from the study showed the mean change in the combined Genant-modified Sharp score(3), which assesses progression of both joint erosion and joint space narrowing, was lower among ACTEMRA (8 mg/kg and 4 mg/kg) plus methotrexate-treated patients versus methotrexate plus placebo-treated patients (0.3, 0.3 versus 1.1, respectively; p<0.001). In addition, the one-year study results showed that 85 percent and 81 percent of patients treated with ACTEMRA (8 mg/kg or 4 mg/kg, respectively) experienced no progression of either joint erosion or joint space narrowing, as measured by the Genant-modified Sharp score, compared with 67 percent of patients treated with placebo plus methotrexate.
ACTEMRA was generally well tolerated; the most common adverse events reported most frequently in the ACTEMRA arms of the LITHE study were serious infections.
About ACTEMRA(R) (tocilizumab)
ACTEMRA is the first humanized interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody being studied for the treatment of RA. Studies demonstrate that reducing the activity of IL-6, one of several key cytokines involved in the inflammatory process, relieves both inflammation of the joints and certain systemic effects of RA. The extensive clinical development program conducted by Roche includes five Phase III clinical studies and has enrolled more than 4,000 patients in 41 countries, including the United States. The five Phase III studies are completed and have reported meeting their primary endpoints. ACTEMRA is currently under review by the FDA in the United States.
ACTEMRA is part of a co-development agreement between Roche and Chugai Pharmaceutical Co. In June 2005, ACTEMRA was launched by Chugai in Japan as a therapy for Castleman's disease; in April 2008, additional indications for rheumatoid arthritis, juvenile idiopathic arthritis and systemic-onset juvenile idiopathic arthritis were also approved in Japan. ACTEMRA (known as RoACTEMRA in Europe), was also recently approved in the European Union, Switzerland and India.
The serious adverse events reported in ACTEMRA clinical studies include serious infections, gastrointestinal perforations and hypersensitivity reactions including anaphylaxis. The most common adverse events reported in clinical studies were upper respiratory tract infection, nasopharyngitis, headache, hypertension and increased ALT. Increases in liver enzymes (ALT and AST) were seen in patients; these increases were generally mild and reversible, with no evidence of hepatic injuries. Laboratory changes, including increases in lipids (total cholesterol, LDL, HDL, triglycerides) and decreases in neutrophils and platelets, were seen in patients without association with clinical outcomes. Treatments that suppress the immune system, such as ACTEMRA, may cause an increase in the risk of malignancies.
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. When approved, ACTEMRA will be the first and only medication to specifically target IL-6 in patients with RA.
About Rheumatoid Arthritis
RA 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 percent 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. For additional information about the U.S. pharmaceuticals business, visit our website http://www.rocheusa.com. Product and treatment information for U.S. healthcare professionals is available at www.RocheExchange.com.
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(1) The Health Assessment Questionnaire Disability Index (HAQ-DI) is a 20-item questionnaire that asks about physical functioning within eight categories (dressing and grooming, arising, eating, walking, hygiene, reach, grip and daily activities). The ability to perform each category is measured on a scale 0 to 3 (0 = no difficulty, 1 = some difficulty, 2 = much difficulty or with assistance, and 3 = unable).
(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 less than or equal to 3.2), moderate (3.2<DAS28 less than or equal to 5.1) or high (DAS28>5.1). DAS28<2.6 corresponds to being in remission according to the criteria of the American College of Rheumatology.
(3) The Genant-modified Sharp score focuses on 14 specific sites for evidence of bone erosion and 13 sites for narrowing of the joint space, both key measures of ongoing structural damage to the joints. Erosion scores are assigned to each of the specified sites, with 0 representing "no erosion" and 3.5 representing "destruction of the joint." Joint space narrowing scores are assigned to each of the specified sites, with 0 representing "no narrowing" and 4 representing "total loss of the joint space." Increases in the scores indicate the extent of additional erosion, joint space narrowing or overall structural damage (both scores combined) that have occurred since treatment began.
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