Fostamatinib effectively increased platelet counts in immune thrombocytopenic purpura

Fostamatinib effectively elevated platelet counts and provided durable response in patients with immune thrombocytopenic purpura (ITP), as shown in phase 3 clinical trials. Thus, fostamatinib can be considered a valuable new treatment approach for ITP.

Prof. Waleed Ghanima (University of Oslo, Norway) presented results of a phase 3 programme that assessed the efficacy, safety, and durability of response of fostamatinib in patients with ITP [1]. In 2 parallel, double-blind, placebo-controlled phase 3 studies (FIT-1 NCT02076412; FIT-2 NCT02076399), 150 patients were randomised 2:1 to receive either 100 mg fostamatinib twice daily (n=101) or placebo (n=49) for 24 weeks, with bi-weekly visits. Patients with a platelet count of <50 x 10⁹/L after 12 weeks or patients who completed 24 weeks of treatment were eligible to enter the FIT-3 trial. FIT-3 (NCT03363334) is an open-label, ongoing extension study to assess the long-term effects of fostamatinib (n=123). Glucocorticoids, azathioprine, or danazol were allowed as concomitant treatment, and rescue medication consisted of intravenous immunoglobulins, anti-D, corticosteroids, and platelet transfusion [2,3]. The primary endpoint in FIT-1 and FIT-2 was stable response, which was considered very restrictive and difficult to achieve.

Pooled results from FIT-1 and FIT-2 showed significantly improved results for patients treated with fostamatinib: 43% achieved overall response compared with 14% with placebo (P=0.0006) and 18% achieved stable response, defined as ≥50 x10⁹ platelets/L in 4 of 6 visits in weeks 14–24. Only 2% of placebo-treated patients showed a stable response (P=0.0003). The median time to first response was 15 days. The incidence of bleeding in patients who received fostamatinib (regardless of responder status) was 29% compared with 37% of those who received placebo. However, no severe or serious bleeding events were experienced by responders. Use of rescue medication was necessary for 30% of fostamatinib-treated and 45% of placebo-treated patients (P=0.07) [2].

Of the 101 fostamatinib-treated patients from FIT-1 and FIT-2, 79 entered FIT-3; 44 out of 49 patients initiated with placebo entered FIT-3. The primary endpoint of the FIT-3 study is stable response, defined as ≥50 x10⁹ platelets/L in ≥1 visit in the first 3 months, followed by platelet counts of ≥50 x10⁹ platelets/L at the subsequent 2 out of 3 monthly visits without use of rescue medication. Fostamatinib is dosed at 100 mg or 150 mg twice daily based on platelet response and tolerability. An interim analysis showed overall response in 48% and stable response in 23% of patients, with 81% of stable responders maintaining a level of ≥50 x 10⁹ platelets/L. No new or more frequent adverse events were detected with long-term use of fostamatinib [3]. Results after 5 years showed increasing platelet counts over time and 70% of patients gaining clinical benefit of ≥30 x 10⁹ platelets/L [4].

In conclusion, fostamatinib effectively elevates platelet counts in adult ITP patients refractory to other treatment, leading to a decrease in bleeding events and in use of rescue medication. Furthermore, fostamatinib has a good safety profile with mostly mild or moderate, easy-to-manage side effects.

1. 
   
   1. Ghanima W. Evidence from clinical trials for the role of fostamatinib in ITP. 2UiHMON-L2, EHA 2021 Virtual Congress, 9–17 June.
   2. Bussel JB, et al. Am J Hematol 2018;93(7):921–30.
   3. Bussel JB, et al. Am J Hematol 2019;94(5):546–53.
   4. Cooper N, et al. Ther Adv Hematol. 2021;12. DOI: 10.1177/20406207211010875.

 

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Posted on 5 August 20215 August 2021