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Hoffmann-La Roche AG (JOBS) Says New Data Confirm Mabthera, Actemra Work


10/27/2008 6:54:39 AM

NUTLEY, N.J., Oct. 25 /PRNewswire/ -- One-year data from a two-year Phase III study demonstrated that ACTEMRA® (tocilizumab) significantly inhibited the progression of structural joint damage in patients with rheumatoid arthritis (RA). Late-breaking results from the LITHE study will be featured as an oral presentation during the American College of Rheumatology (ACR) Annual Scientific Meeting (October 24-28) in San Francisco. Fourteen additional abstracts, which evaluate ACTEMRA, a novel interleukin-6 (IL-6) receptor inhibitor, in patients with moderately to severely active RA, will also be presented during the meeting.

"The LITHE study demonstrated that treatment with ACTEMRA inhibited structural joint damage, which is a major cause of disability and loss of physical function for RA patients," said Joel Kremer, M.D., investigator in the LITHE study and Director of Research at The Center for Rheumatology in Albany, New York. "It is critical to stop joint damage as quickly as possible to avoid joint deformity and to help patients maintain their quality of life."

In the study, the mean change in the combined Genant-modified Sharp score(1), 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 study 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.

Importantly, data from the LITHE study also showed that patients treated with ACTEMRA (8 mg/kg or 4 mg/kg) plus methotrexate experienced a reduction in disease signs and symptoms at one year compared with patients treated with placebo plus methotrexate. At 52 weeks, 56 percent, 36 percent and 20 percent of RA patients treated with ACTEMRA 8 mg/kg plus methotrexate achieved ACR20, ACR50 and ACR70(2), respectively, and 47 percent, 29 percent and 16 percent of patients in the ACTEMRA 4 mg/kg arm achieved these ACR scores, respectively. In contrast, 25 percent, 10 percent and 4 percent of patients in the control group achieved ACR20, ACR50 and ACR70, respectively. Disease remission (DAS28 <2.6)(3) was demonstrated in 47 percent and 30 percent of patients treated with ACTEMRA 8 mg/kg and 4 mg/kg, respectively, at week 52 compared with 8 percent of patients treated with placebo plus methotrexate.

"We've seen in previous studies that patients treated with ACTEMRA experienced an improvement in the signs and symptoms of RA and achieved remission according to the DAS28 criteria more often than with DMARDs," said Kenneth Bahrt, M.D., Global Medical Director, Autoimmunity, Roche. "The LITHE study not only confirmed these data, but for the first time demonstrated that ACTEMRA also significantly inhibited the progression of structural joint damage in patients with RA."

At one year, the study also showed that there was improved physical function following treatment with ACTEMRA, as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI).(4)

About the LITHE Study

LITHE (TociLIzumab Safety and THE Prevention of Structural Joint Damage), a three-arm, randomized, double-blind, placebo-controlled study, was designed to evaluate the efficacy and safety of ACTEMRA (8 mg/kg or 4 mg/kg) plus methotrexate compared with placebo plus methotrexate in RA patients for the prevention of structural joint damage, improvement in physical function and disease signs and symptoms. Patients received either ACTEMRA

intravenously every four weeks plus methotrexate weekly or placebo infusions every four weeks plus methotrexate weekly. The study included nearly 1,200 patients from 137 sites in 15 countries, including the United States.

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® (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. Four Phase III studies are completed and have reported meeting their primary endpoints. A fifth Phase III study, the LITHE study evaluating ACTEMRA in RA is an ongoing two-year study, which is expected to report complete data evaluating the effects of ACTEMRA on the inhibition of structural joint damage in 2009. ACTEMRA is currently under review in the United States and Europe.

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.

The serious adverse reactions reported in ACTEMRA clinical studies include serious infections, gastrointestinal perforations and hypersensitivity reactions including anaphylaxis. The most common adverse reactions 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.

About IL-6

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

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 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.

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, 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: www.rocheusa.com or www.roche.us.

All trademarks used or mentioned in this release are protected by law.

(1) 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.

(2) ACR20, ACR50 and ACR70 represent the percentage of reduction (20%, 50% or 70%) in certain RA symptoms and measures the number of tender and swollen joints, pain, patient's and physician's global assessments and certain laboratory markers. An ACR70 response is considered exceptional and represents a significant improvement in a patient's condition.

(3) 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 (3.25.1). DAS28<2.6 corresponds to being in remission according to the criteria of the American College of Rheumatology.

(4) 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).

Source: Hoffmann-La Roche Inc.


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