Fostamatinib, sold under the brand names Tavalisse and Tavlesse, is a tyrosine kinase inhibitor medication for the treatment of chronic immune thrombocytopenia (ITP).

Chronic immune thrombocytopenia is an autoimmune bleeding disorder where the blood doesn't clot as it should because of a low platelet count.

[9] When FcγRs I, IIA, and IIIA bind to their ligands, the receptor complex becomes activated and triggers the phosphorylation of the immunoreceptor-activating motifs (ITAMs).

Because Syk plays an important role in FcγR-mediated signal transduction and inflammatory propagation, it is considered a good target for the inhibition of various autoimmune conditions, including rheumatoid arthritis and lymphoma.

In animal models, treatment with R406/R788 was shown to be safe and effective in reducing inflammation and joint damage in immune-mediated rheumatoid arthritis.

Human studies have shown that R788 has good oral bioavailability, biologic activity, is well tolerated, and does not exhibit collagen or ADP-induced platelet aggregation.

[13][14] A phase II study of rheumatoid arthritis patients failing to respond to a biologic agent showed little efficacy as compared to placebo, but the drug was well tolerated.

Patients with ITP have accelerated clearance of circulating IgG-coated platelets via Fcγ receptor-bearing macrophages in the spleen and liver, leading to different levels of thrombocytopenia and variable degrees of mucocutaneous bleeding.

Many patients exhibit responses to established therapies, including corticosteroids, IV immunoglobulin, anti-D, splenectomy, and rituximab.

Several thrombopoiesis-stimulating therapies including eltrombopag and romiplostim are being investigated to help combat low platelet counts in ITP patients.

Rigel reported results from two Phase III clinical trials for fostamatinib as an ITP treatment in August and October 2016.

The study is currently recruiting participants from U.S. states including Arizona, California, D.C., Massachusetts, New York, North Carolina, and Texas.

Eligible candidates cannot have recently used cyclophosphamide, mycophenolate mofetil, azathioprine, Rituximab, or > 15 mg/day of prednisone or any other corticosteroid equivalent.

[20][4][6] The U.S. Food and Drug Administration (FDA) approved fostamatinib based on evidence from two identical, double-blind, placebo-controlled clinical trials, FIT-1 (NCT02076399) and FIT-2 (NCT02076412) of 150 adults with persistent or chronic ITP who had an insufficient response to previous treatment, which included corticosteroids, immunoglobulins, splenectomy, and/or a thrombopoietin receptor agonist.

[4] The FIT-2 trial was conducted at 23 sites in Austria, Bulgaria, Czech Republic, Germany, Norway, Poland, Romania, and Spain.