Saturday, Oct 17, 2009
Philadelphia -- October 17, 2009 --Genentech, Inc., a wholly-owned member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced two-year results from a Phase III study, which showed that people with rheumatoid arthritis (RA) who received either a 4 mg/kg or 8 mg/kg dose of ACTEMRA® (tocilizumab), in combination with methotrexate, had no progression of joint damage, (75 and 83 percent, respectively, as assessed by radiograph) compared with people who received methotrexate alone (66 percent). The overall safety profile of ACTEMRA was consistent across all global clinical studies. The study, known as LITHE, will be featured as an oral presentation during the American College of Rheumatology (ACR) Annual Scientific Meeting along with results from two additional studies evaluating the long-term use of ACTEMRA in people with RA.
The LITHE study also showed that people who received either dose of ACTEMRA plus methotrexate showed significant improvement in physical function, compared with people who received methotrexate plus placebo, as measured by the mean area under the curve (AUC) of the Health Assessment Questionnaire Disability Index (HAQ-DI)i change from baseline. In addition, 65 percent of people who received ACTEMRA (8 mg/kg) plus methotrexate for two years had their disease go into remission compared with 48 percent of people treated for just one year. In this study, remission was defined by achieving a disease activity score (called DAS28) of less than 2.6.ii DAS28 is a commonly used tool that assesses a variety of measures, including swollen and tender joints at multiple time points.
"Two primary goals in treating RA are keeping the disease in remission for as long as possible and reducing the amount of joint damage that occurs," said Hal Barron, M.D., executive vice president, Global Development and chief medical officer, Genentech. "This study showed that ACTEMRA both improved physical function and delayed progression of joint damage in people with moderate to severe RA and importantly, that benefit was sustained for two years."
Pooled Long-Term Efficacy and Safety Analyses
Pooled data from three Phase III pivotal studies, including LITHE, and two long-term extension studies, showed that at week 48 and beyond more than one third of people who had previously failed disease modifying anti-rheumatic drugs (DMARDs) and received either dose of ACTEMRA achieved disease remission, as defined by a disease activity score (DAS28) of less than 2.6, regardless of prior treatment history or disease duration.
An additional analysis presented at the meeting showed that no new safety signals have emerged with people who received ACTEMRA over an average duration of nearly two and a half years, and the overall safety profile of ACTEMRA was consistent with previous experience.
About the Studies
LITHE (TociLIzumab Safety and THE Prevention of Structural Joint Damage) was a three-arm, randomized, double-blind, placebo-controlled study in the first year with people receiving either 4 mg/kg or 8 mg/kg of ACTEMRA, and either a double-blind or an open-label study with the majority of people receiving ACTEMRA 8 mg/kg in the second year. The study was designed to evaluate the safety and efficacy profile of ACTEMRA plus methotrexate compared with placebo plus methotrexate for the prevention of structural joint damage and improvement in physical function over two years in people with RA.
The study evaluated nearly 1,200 people with RA at 137 sites in 15 countries, including the United States. The overall safety profile of ACTEMRA was consistent across all global clinical studies. The most common individual serious adverse events (SAEs) were serious infections such as pneumonia, cellulitis, gastroenteritis and bronchitis. The most frequent individual adverse events (AEs) were upper respiratory infection, bronchitis, urinary tract infection, hypertension, nasopharyngitis and increased transaminases.
The pooled long-term efficacy and safety analyses included all participants from five pivotal Phase III, randomized, controlled studies (OPTION, TOWARD, RADIATE, AMBITION, and LITHE one year) and two long-term extension studies (GROWTH95 and GROWTH96) to examine the safety and efficacy profile of ACTEMRA across different RA populations: DMARD-IR (inadequate response), anti-TNF-IR and monotherapy.
The analyses each evaluated approximately 4,000 people with RA, throughout the world. The overall safety profile of ACTEMRA was consistent across all global clinical studies. The SAEs reported most frequently in the ACTEMRA arms of the studies were pneumonia, and the most common AEs reported were upper respiratory tract 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 ACTEMRA clinical development program includes five Phase III clinical studies and has enrolled more than 4,000 people with RA in 41 countries, including the United States. All five Phase III studies are completed and have reported meeting their primary endpoints. ACTEMRA is currently being reviewed by the U.S. Food and Drug Administration (FDA).
ACTEMRA is part of a co-development agreement with 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 RA, juvenile idiopathic arthritis and systemic-onset juvenile idiopathic arthritis were also approved in Japan. ACTEMRA is known as RoACTEMRA in the European Union, and is approved in several other countries, including India, Brazil, Switzerland and Australia, in combination with methotrexate for the treatment of adult patients with moderate to severe RA who have either responded inadequately to, or who were intolerant to, previous therapy with one or more disease modifying anti-rheumatic drugs or tumor necrosis factor antagonists. In these patients, RoACTEMRA can be given as monotherapy in cases of intolerance to methotrexate or where continued treatment with methotrexate is inappropriate.
The SAEs reported in ACTEMRA clinical studies include serious infections, gastrointestinal perforations and hypersensitivity reactions including anaphylaxis. The most common AEs 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 and 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. If approved by the FDA, 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.
Founded more than 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. The company, a wholly-owned member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.
i 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).
ii 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