Genentech, Inc., a wholly-owned member of the Roche Group announced that the company submitted a supplemental Biologics License Application (sBLA) to the US 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 tumour 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 per cent 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.
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 tumour 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 programme 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.
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.
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.