Rigel Pharmaceuticals, Inc, (SOUTH SAN FRANCISCO, California) announced that it has initiated enrollment and dosing of patients with refractory immune thrombocytopenic purpura (ITP) in a phase II study evaluating the efficacy and safety of its lead product candidate, R788, an oral syk kinase inhibitor that inhibits IgG signaling and blocks the activation of mast cells, macrophages and B-cells that promote swelling and an inflammatory response. This single-center, ascending dose proof-of-concept study will evaluate several doses of R788. The study is expected to enroll up to 20 patients in the US who have chronic refractory ITP. The primary endpoint of this study is improved platelet counts. The study will also measure the safety of R788 in these patients.

ITP is an autoimmune hematological disease characterized by platelet destruction mediated by IgG signaling, causing spontaneous bleeding. Current first-line treatment for ITP consists primarily of steroids, which are initially effective in 50–75% of cases, but then show a decline in efficacy over time. Failure of first-line medical therapy can lead to removal of the spleen, which poses the risk of other significant complications. Sustained remission with chronic ITP is infrequent, making the need for new therapies necessary. Rigel's R788 targets IgG signaling and so addresses an underlying autoimmune cause of the disease, rather than stimulating platelet production. In preclinical studies, Rigel has shown R788 to improve platelet counts in mice treated with antiplatelet antibodies thus mitigating the disease in an ITP mouse model.

Phase I trial results have demonstrated that R788 is well-tolerated and showed good pharmaceutical properties, and pharmacokinetic/pharmacodynamic data demonstrated a strong correlation between drug plasma levels and the inhibition of the drug target. In addition to ITP, Rigel is studying R788 in a phase II study for the treatment of rheumatoid arthritis.

—A. Techman

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