Roche has announced that Radiate, the third study in Actemra's (tocilizumab) extensive multinational phase III development programme, successfully met its primary endpoint. The study examined Actemra in combination with methotrexate in rheumatoid arthritis (RA) patients who had an inadequate response to anti-tumour necrosis factor therapy (anti-TNFs).
The study conducted in 498 patients with difficult-to-treat RA disease, showed that a greater proportion of patients treated with Actemra plus methotrexate, achieved a significant improvement in disease signs and symptoms (ACR scores) following 24 weeks of treatment, compared to patients treated with placebo plus methotrexate.
"Radiate's positive outcome further confirms the critical role of IL-6 in the pathophysiology of rheumatoid arthritis," said Urs Schleuniger, Business Director, Inflammation and Autoimmune Disease, Roche Pharmaceuticals. "These results add to the wealth of data being compiled ahead of the anticipated regulatory filing later this year," he added.
The Radiate study was a three-arm, randomised, double-blind, placebo-controlled study of the safety and reduction of signs and symptoms during treatment with Actemra (4mg/kg or 8mg/kg) versus placebo, in combination with methotrexate, in patients with moderate to severe active RA with an inadequate response to at least one anti-TNF therapy. Traditionally this patient group have more refractory disease and prove more difficult to treat. The study involved treating 498 patients randomised across three treatment groups and was conducted at 128 trial sites in 13 countries, including the United States. Each group of patients either received 4mg/kg or 8mg/kg Actemra, or placebo in addition to 10-25mg methotrexate weekly.
Data from the Radiate study will be submitted for presentation at future international scientific meetings. Roche's global Actemra phase III clinical development programme has two further studies underway, one of which is scheduled to report in 2007.
At the EULARConference in June, the OPTION study reported that treatment with Actemra plus methotrexate resulted in a rapid and significant improvement of RA signs and symptoms in patients who had an inadequate response to methotrexate. Additionally, the TOWARD trial successfully met its primary endpoint (ACR20) and demonstrated Actemra's efficacy in patients who had an inadequate response to traditional disease modifying drugs (DMARDs).
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 most frequent adverse events reported are upper respiratory tract infections, headache, nasopharyngitis and hypertension. As with other biological disease modifying anti-rheumatic drugs (DMARDs), serious infections have been reported in some patients treated with Actemra.
Roche and Chugai are collaborating on a phase III clinical development programme in RA running outside Japan, with more than 4000 patients enrolled in 41 countries including several European countries and the USA. In Japan, Actemra was launched 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.