A Phase I clinical trial has been initiated to study the safety and pharmacokinetics of a novel candidate drug for rheumatoid arthritis (RA), R406, an orally administered small molecule syk kinase inhibitor that blocks both IgG and IgE activation of mast cells, macrophages, and B cells. The escalating single-dose, placebo-controlled clinical trial will include 36 healthy volunteers and will be followed by a multiple dose study including an additional 24 subjects. Rigel Pharmaceuticals, Inc, indicates that the results of the trial are expected by the second half of 2005.

R406, which has been shown to be effective in several rodent models of arthritis, blocks production of inflammatory response mediators such as TNF-α and various interleukins that lead to swelling, inflammation, and bone damage. Designed to prevent bone and cartilage damage, a dose of 3mg/kg R406 prevented inflammation leading to bone and structural joint damage in a mouse RA model, and it appears to be well tolerated even at much higher doses. Data from a 28-day study in a rat collagen-induced arthritis model demonstrated that R406 afforded a significant dose-related reduction in arthritis severity that was evident within 7 days of therapy and improved throughout the study. R406 also has the potential to be effective in treating other autoimmune diseases such as psoriasis, inflammatory bowel disease, and multiple sclerosis.