Syk Inhibitor Fostamatinib: A Novel Treatment for Chronic Immune Thrombocytopenia

Chronic immune thrombocytopenia (ITP) is a disorder in which the immune system produces antibodies that target and destroy platelets, the blood cells that are responsible for clotting. This leads to low platelet count and increased risk of bleeding. ITP affects about 1 in 10,000 people and can cause serious complications such as gastrointestinal or intracranial hemorrhage ¹.

The main goal of ITP treatment is to increase the platelet count to a safe level and prevent major bleeding events. However, not all patients respond well to the available therapies, which include steroids, splenectomy, rituximab, and thrombopoietin (TPO) mimetics. These therapies have various limitations, such as side effects, relapse rates, infection risk, thrombosis risk, and continuous administration ².

Fostamatinib is a new drug that offers a different mechanism of action for treating ITP. It is the first spleen tyrosine kinase (Syk) inhibitor approved for ITP treatment in adult patients who have had an insufficient response to previous therapy ³. Syk is an enzyme that plays a key role in the activation of macrophages, the immune cells that engulf and destroy platelets coated with antibodies. By blocking Syk, fostamatinib reduces the antibody-mediated platelet destruction and allows the platelet count to rise ⁴.

Fostamatinib was evaluated in two phase III randomized controlled trials (FIT1 and FIT2) involving 150 patients with chronic ITP who had failed at least one prior treatment. The patients received either fostamatinib or placebo twice daily for 24 weeks. The primary endpoint was stable response, defined as achieving and maintaining a platelet count of at least 50,000/µL for at least four consecutive weeks ⁵.

The results showed that fostamatinib significantly increased the stable response rate compared to placebo (18% vs 2% in FIT1 and 16% vs 4% in FIT2). The pooled analysis of both studies also showed that fostamatinib significantly increased the overall response rate (28% vs 4%) and the median duration of response (12.4 vs 1.0 weeks). Fostamatinib also improved the bleeding symptoms and quality of life of the patients ⁵.

The long-term efficacy and safety of fostamatinib were further assessed in an open-label extension study (FIT3), which enrolled 101 patients from FIT1 and FIT2 who completed or failed the initial treatment period. The patients received fostamatinib for up to 62 months (median duration 6 months). The interim results showed that fostamatinib maintained or improved the platelet response in most patients, including those who received it as second- or later-line therapy. The most common adverse events were diarrhea, hypertension, nausea, and increased liver enzymes ⁶.

Fostamatinib is an oral drug that can be taken twice daily with or without food. The recommended starting dose is 100 mg twice daily, which can be increased to 150 mg twice daily after four weeks if the platelet count is below 50,000/µL. The dose should be reduced or discontinued if the platelet count exceeds 200,000/µL or if severe adverse events occur .

Fostamatinib is a novel treatment option for chronic ITP that targets a different pathway of platelet destruction than the existing therapies. It has shown to be effective and generally well-tolerated in clinical trials involving patients who had an insufficient response to previous treatment. Fostamatinib may offer a new hope for patients with refractory ITP who need an alternative therapy to achieve a safe platelet count and reduce bleeding risk.

References

¹ : Fostamatinib - Wikipedia ² : Fostamatinib for the treatment of chronic immune thrombocytopenia ³ : Fostamatinib: A Review in Chronic Immune Thrombocytopenia ⁴ : R406 besylate | Syk inhibitor - Active metabolite of Fostamatinib … ⁵: Bussel JB, Arnold DM, Grossbard E, et al. Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: results of two phase 3, randomized, placebo-controlled trials. Am J Hematol. 2018;93(7):921-930. ⁶: Bussel JB, Kuter DJ, Pullarkat V, et al. Long-term fostamatinib treatment of adults with immune thrombocytopenia (ITP): final analysis of an open-label extension study. Blood Adv. 2020;4(24):6110-6120. : Tavalisse (fostamatinib) [prescribing information]. South San Francisco, CA: Rigel Pharmaceuticals, Inc.; 2018.