Roche said that it has submitted a biologics license application (BLA) to the US Food and Drug Administration (FDA) seeking approval for Actemra (tocilizumab) to reduce the signs and symptoms with moderate to severe rheumatoid arthritis (RA) in adults.

The company has also plans to file a Marketing Authorisation Application (MAA) for the product with the European Medicines Agency (EMEA) in early December.

"The filing for Actemra in the US is an important milestone for Roche, and brings us another step closer to making this therapy available to the millions of patients in the United States who suffer from the pain and debilitating effects of rheumatoid arthritis," said William M. Burns, CEO, pharmaceuticals division, Roche.

Actemra is the first humanized interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody and represents a novel mechanism of action to treat RA. Research suggests that reducing the activity of IL-6, one of several key cytokines involved in the inflammatory process, may reduce inflammation of the joints and relieve certain systemic effects of RA.

The BLA submission to the FDA is based on results from five international phase III studies which demonstrated Actemra as monotherapy or in combination with disease modifying anti-rheumatic drugs (DMARDs) such as methotrexate significantly reduced the signs and symptoms of rheumatoid arthritis, as measured by ACR and disease activity score (DAS) remission rates, compared with DMARD therapies alone. Furthermore, patients who had previously failed anti-tumour necrosis factor (anti-TNF) treatments also showed significant improvement in signs and symptoms of RA after treatment with Actemra.

The clinical development programme conducted by Roche includes five clinical studies and has enrolled more than 4,000 patients in 40 countries, including the US and Europe. One of these phase III trials evaluating Actemra in RA is an ongoing two-year study and is expected to report one-year data evaluating the effect of Actemra on the inhibition of structural damage in 2008.

Actemra is the result of research collaboration by Chugai and is being co-developed globally with Chugai. Actemra is the first humanised interleukin-6 (IL-6) receptor inhibiting monoclonal antibody and represents a novel mechanism of action to treat RA, a disease with a high unmet medical need. The overall safety profile observed in the global studies of Actemra is consistent and Actemra is generally well tolerated. The serious adverse events reported in Actemra global clinical studies included serious infections and hypersensitivity reactions including a few cases of anaphylaxis. The most common adverse events reported in clinical studies were upper respiratory tract infection, nasopharyngitis, headache, hypertension, increases in liver function tests (ALT and AST) were seen in some patients. These increases were generally mild and reversible, with no hepatic injuries or any observed impact on liver function.

Roche and Chugai are collaborating on a phase III clinical development programme in RA running outside Japan, with more than 4000 patients enrolled in 40 countries including several European countries and the USA. In Japan, Chugai launched Actemra in June 2005 as a therapy for Castleman's disease and in April 2006 filed for the additional indications of rheumatoid arthritis and systemic-onset juvenile idiopathic arthritis.