Rigel Pharmaceuticals Inc is developing fostamatinib, a prodrug of the spleen 
tyrosine kinase (Syk) inhibitor R-406, for the potential treatment of autoimmune 
diseases such as rheumatoid arthritis (RA), idiopathic thrombocytopenic purpura 
(ITP) and B-cell lymphomas. Syk is a key mediator of Fc and B-cell receptor 
signaling in inflammatory cells, such as B-cells, mast cells, macrophages and 
neutrophils. Preclinical studies of R-406 or fostamatinib demonstrated a 
significant reduction in major inflammatory mediators such as TNFalpha, IL-1, 
IL-6 and IL-18, leading to reduced inflammation and bone degradation in models 
of RA. In a phase II clinical trial, fostamatinib treatment effectively improved 
American College of Rheumatology response rates in patients with RA. Preclinical 
studies and phase II trials also suggested the potential of using fostamatinib 
for the treatment of ITP and B-cell lymphomas, by increasing platelet counts and 
inducing response rates, respectively. Fostamatinib is orally bioavailable and 
was well tolerated in phase I and II trials, with the most common side effect 
being gastrointestinal symptoms. At the time of publication, phase II trials for 
fostamatinib were ongoing in patients with RA, ITP and B-cell lymphomas. The Syk 
inhibitor appears to be a promising therapeutic for immunological diseases, but 
further data are required to establish the efficacy and long-term safety of the 
drug in humans.