Tuesday, Mar 16, 2010
South San Francisco, Calif. -- March 16, 2010 --Genentech, Inc., a wholly-owned member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the company submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) for ACTEMRA® (tocilizumab) for the prevention of structural joint damage (as assessed by radiograph) and improvement in physical function in adults with moderately to severely active rheumatoid arthritis (RA). ACTEMRA was approved by the FDA on January 8, 2010 as the first interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody to treat RA in adult patients after an inadequate response to at least one other medicine called a tumor necrosis factor (TNF) antagonist.
The application is based on positive results from the Phase III LITHE trial which showed that patients receiving ACTEMRA in combination with methotrexate (MTX) had significantly less damage to their joints at two years, compared to patients who received MTX alone. The outcome was determined by x-rays, which measured over time the progression of bone erosions and narrowing of joint spaces. In addition, the data showed that with long-term use, patients with rheumatoid arthritis treated with ACTEMRA 8mg/kg plus MTX suffered 81% less damage to their joints compared to those treated with MTX alone at Week 104 based on Total-Sharp Genant Score. Patients treated with 4 mg/kg plus MTX also had a statistically significant reduction in Total-Sharp Genant Score at Week 104 of therapy.
The LITHE study also showed that patients who received either dose of ACTEMRA plus methotrexate showed significant improvement in physical function, compared with patients who received methotrexate plus placebo at Weeks 52 and 104, as measured by the mean area under the curve (AUC) of the Health Assessment Questionnaire Disability Index (HAQ-DI)1 change from baseline.
"These data suggest that in addition to reducing the painful signs and symptoms of RA, ACTEMRA inhibits the progression of the disease by reducing long-term joint damage and improves physical function which are important goals of treating this chronic, debilitating disease," said Hal Barron, M.D., head, Global Development and chief medical officer at Roche.
About the LITHE (TociLIzumab Safety and THE Prevention of Structural Joint Damage) Study
The LITHE study, a randomized, double-blind, placebo-controlled trial was designed to evaluate the efficacy of TCZ plus MTX in preventing structural joint damage and improving physical function over two years. LITHE was an international study, including 15 countries and 1196 patients with moderate to severe RA who had an inadequate response to MTX. In this randomized study, patients received either ACTEMRA (4 mg/kg or 8 mg/kg, one infusion every four weeks) in combination with MTX or MTX alone. Results from the 24-month analysis showed that at 104 weeks, total Genant-modified Sharp Score change from baseline for the ACTEMRA 8mg + MTX, 4mg +MTX, and MTX alone groups were: 0.37, 0.58 and 1.96 respectively. The HAQ-DI AUC change from baseline, adjusted mean scores were: -144.1, -128.4 and -58.1 respectively at Week 52.
About ACTEMRA® (tocilizumab)
ACTEMRA is the first humanized IL-6 receptor-inhibiting monoclonal antibody approved for the treatment of adult patients with moderately to severely active RA who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies. 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 symptoms of RA. The extensive ACTEMRA clinical development program included five Phase III clinical studies and enrolled more than 4,000 people with RA in 41 countries, including the United States.
Serious side effects associated with ACTEMRA include serious infections that may lead to hospitalization or death, gastrointestinal perforations (a hole in the stomach or intestines), and hypersensitivity reactions including anaphylaxis. The most common adverse events reported in clinical studies were upper respiratory tract infection, nasopharyngitis (inflammation of the nose and throat), headache, high blood pressure and increased liver enzymes. The increases in liver enzymes that were seen in patients were generally mild and reversible and did not result in apparent permanent or clinically evident hepatic injury. Laboratory changes, including increases in total cholesterol, the amount of fat circulating in the blood, and decreases in neutrophils (one of the cell types that helps fight infections) and platelets, were seen. Treatments that suppress the immune system, such as ACTEMRA, may cause an increase in the risk of cancer. For additional important safety information, including Boxed WARNINGS and Medication Guide, please visit http://www.actemra.com or call 1-800-ACTEMRA (228-3672).
ACTEMRA is part of a co-development agreement with Chugai Pharmaceutical Co. and has been approved in Japan since June 2005. ACTEMRA is approved in the European Union, where it is known as RoACTEMRA, and several other countries, including India, Brazil, Switzerland and Australia.
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. According to the Arthritis Foundation, RA affects approximately 1.3 million adults 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.
1The 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).