April 19, 2018—On Tuesday, the U.S. Food and Drug Administration (FDA) approved the use of fostamatinib disodium hexahydrate, a Syk inhibitor, for the second-line treatment of adult patients with thrombocytopenia resulting from chronic ITP.
Chronic immune thrombocytopenia, sometimes known as idiopathic thrombocytopenic purpura, or just ITP, is an acquired autoimmune disorder characterized by the impaired production and accelerated destruction of platelets in the blood. A relatively uncommon hematologic disorder, ITP is observed in 2-6 people per 100,000 per year.
ITP varies by age, symptoms, and level of bleeding with treatment historically including observation, corticosteroids, and splenectomy. In 2008, treatment options for ITP expanded to include the thrombopoietin receptor agonists romiplostim and eltrombopag. Treatment options expanded again this week with the approval of fostamatinib.
Fostamatinib, a spleen tyrosine kinase (Syk) inhibitor, has been shown to reduce platelet destruction in patients with ITP via the inhibition of macrocyte phagocytosis. This approval was based on the results of two identical, double-blind, placebo-controlled trials, FIT-1 (NCT02076399) and FIT-2 (NCT02076412). Across both trials, a total of 150 patients with persistent or chronic ITP previously treated with corticosteroids, immunoglobulins, splenectomy, and/or a thrombopoietin receptor agonist were randomized 2:1 to receive 100 mg fostamatinib twice daily, or placebo, for 24 weeks.
Results recently presented at the 2017 Annual Meeting & Exposition of the American Society of Hematologists established the efficacy of fostamatinib in these patients. A stable platelet response (defined as platelet levels of at least 50 x 109/L for at least 4 of 6 measurements after week 14) was overserved in 18% (n=9) of patients in FIT-1 and 16% (n=8) of patients in FIT-2. In the FIT-3 extension study (NCT02077192), a further 23% (n=10) of patients demonstrated a stable response when exposed to fostamatinib.
The most common adverse events in patients treated with fostamatinib included diarrhea, hypertension, nausea, dizziness, elevated liver enzyme levels, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia.
In addition to ITP, fostamatinib is currently under clinical investigation in patients with B-cell and T-cell lymphoma, solid tumors, rheumatoid arthritis, and other diseases.
Full prescribing information for fostamatinib is available here.
Jonathan A. Bell
Published Online: Thursday, April 19, 2018