Fostamatinib Receives FDA Approval for Immune Thrombocytopenic Purpura (ITP)

On 17 April 2018, the United States Food and Drug Administration, FDA, approved fostamatinib disodium hexahydrate tablets (Tavalisse) to treat thrombocytopenia in adults with chronic immune thrombocytopenia (ITP).

Immune thrombocytopenia (ITP)is a type of thrombocytopenic purpura, or rash, defined by a low platelet count despite normal bone marrow and the absence of other causes of thrombocytopenia. It causes a characteristic purpuric rash and increased bleeding tendency. Two distinct clinical syndromes occur: an acute condition in children and a chronic one in adults. The acute form generally follows an infection and resolves spontaneously within two months. Chronic immune thrombocytopenia, the adult form, is thrombocytopenia lasting more than six months without a known specific cause.

Approval was based on two similar double-blind, placebo-controlled trials involving 150 patients with refractory or chronic ITP inadequately responsive to previous corticosteroids, immunoglobulins, splenectomy and/or thrombopoietin receptor agonists: FIT-1 (NCT02076399) and FIT-2 (NCT02076412), the clinical trials in question. For 24 weeks, patients received fostamatinib (100 mg twice daily) or placebo according to randomization (2:1); after one month, the study allowed dose increases to oral 150 mg twice daily.

Fostamatinib efficacy was based on stable platelet response (between weeks 14 and 24, among 6 visits, at least 4 with at least 50 x109/L). In FIT-1, no placebo patients had a stable response [%0 (n=0)], versus %18 (n = 9) receiving fostamatinib (p=0.03). In FIT-2, stable platelet responses occurred in %16 (n=8) on fostamatinib and %4 (n=1) on placebo (p=0.26). In the extension FIT-3 (NCT 02077192), %23 (n= 10) newly starting fostamatinib had a stable response. Long-lasting platelet responses occurred across FIT-1, FIT-2 and extension FIT-3.

The most common effects occurring in at least %5 of fostamatinib-treated patients were side effects including diarrhea, hypertension, nausea, dizziness, abnormal liver function tests (increased ALT/AST), respiratory infection, rash, abdominal pain, fatigue, chest pain and low white blood cell counts. Serious adverse effects (%1) observed with fostamatinib in double-blind ITP studies were febrile neutropenia, diarrhea, respiratory infection and hypertensive crisis.

The recommended starting fostamatinib dose is oral 100 mg twice daily. After one month, if the platelet count has not reached at least 50x109/L, it may be increased to 150 mg twice daily.