AstraZeneca initiates phase III clinical development of fostamatinib for the treatment of rheumatoid arthritis

AstraZeneca today announced the enrollment of the first patient in the phase III clinical development programme for fostamatinib, a novel oral syk inhibitor. The phase III programme, called OSKIRA (Oral Syk Inhibition in Rheumatoid Arthritis), is designed to investigate fostamatinib as a treatment for rheumatoid arthritis (RA) in patients with an inadequate response to disease modifying anti-rheumatic drugs (DMARDs), including methotrexate (MTX).

The OSKIRA clinical trial programme will include three pivotal phase III studies assessing the efficacy and tolerability of fostamatinib; two 12-month studies examining the effect of fostamatinib on patients responding inadequately to DMARDs including MTX, and a six-month study assessing the effect of fostamatinib on patients who have previously responded inadequately to anti-TNF therapy. The fostamatinib programme will also include long-term safety extension studies involving more than 2,000 of the patients recruited during the course of the phase II and III programmes.

“We are delighted that the OSKIRA clinical trial programme for fostamatinib has begun,” said Anders Ekblom, AstraZeneca’s Executive Vice President of Global Medicines Development. “Patients with rheumatoid arthritis currently have limited treatment options after they stop responding adequately to DMARDs or anti-TNF therapy, and we are hopeful that fostamatinib may represent a novel alternative for patients to help manage their condition beyond this stage.”

All three pivotal studies start with a six-month double-blind, randomised, placebo-controlled period, and the two 12-month studies also include a six-month active-extension period. The primary outcome measures across the three studies include ACR 20* response rate at six months, and one of the 12-month studies also includes the change in structural progression at six months as a primary endpoint. Two dose regimens of fostamatinib will be evaluated in the phase III programme; a 100mg twice daily regimen and a second regimen investigating 100mg twice daily for four weeks followed by a maintenance dose of 150mg once daily.

Fostamatinib, previously referred to as R788, is the first oral syk inhibitor in development, and as such, represents a novel therapeutic approach for RA. A phase II programme has recently been completed, which demonstrated positive results in patients with rheumatoid arthritis who were responding inadequately to ongoing treatment with MTX. This six-month study data, known as TASKi2, was recently published in the online edition of the New England Journal of Medicine on September 22, 2010.

The first anticipated regulatory filings based on the OSKIRA programme are planned for 2013. Fostamatinib was in-licensed by AstraZeneca from Rigel Pharmaceuticals, Inc. in February 2010.