Fostamatinib produces clinically meaningful responses in adults with immune thrombocytopenia (ITP), according a study published in the July issue of the American Journal of Hematology.
James Bussel, M.D., from Weill Cornell Medicine in New York City, and colleagues conducted two parallel phase 3 trials in which patients with persistent/chronic ITP (median duration, 8.5 years) were randomized in a 2-to-1 ratio to fostamatinib (101 patients) or placebo (49 patients), at 100 mg twice daily for 24 weeks, with a dose increase to 150 mg twice daily after four weeks in non-responders.
The researchers found that stable responses occurred in 18% of patients on fostamatinib versus 2% on placebo. 43% of patients on fostamatinib and 14% on placebo achieved overall responses (defined as ≥1 platelet count ≥50,000/μL within the first 12 weeks on treatment).
With the 100 mg dosage, the median time to response was 15 days, and 83% responded within eight weeks. Diarrhea, hypertension, nausea, dizziness, and alanine aminotransferase increase were the most common adverse events and were all more frequent with fostamatinib versus placebo.
However, most adverse events were mild or moderate and resolved spontaneously or with medical management. "Fostamatinib is a novel ITP treatment option that targets an important mechanism of ITP pathogenesis," the authors noted.
Several authors disclosed financial ties to pharmaceutical companies, including Rigel Pharmaceuticals, which manufactures fostamatinib and funded the study.
Spleen tyrosine kinase (Syk) signaling is central to phagocytosis?based, antibody?mediated platelet destruction in adults with immune thrombocytopenia (ITP). Fostamatinib, an oral Syk inhibitor, produced sustained on?treatment responses in a phase 2 ITP study.
In two parallel, phase 3, multicenter, randomized, double?blind, placebo?controlled trials (FIT1 and FIT2), patients with persistent/chronic ITP were randomized 2:1 to fostamatinib (n = 101) or placebo (n = 49) at 100 mg BID for 24 weeks with a dose increase in nonresponders to 150 mg BID after 4 weeks.
The primary endpoint was a stable response (platelets ≥50 000/μL at ≥4 of 6 biweekly visits, weeks 14?24, without rescue therapy). Baseline median platelet count was 16 000/μL; median duration of ITP was 8.5 years.
Stable responses occurred in 18% of patients on fostamatinib vs. 2% on placebo (P = .0003). Overall responses (defined retrospectively as ≥1 platelet count ≥50 000/μL within the first 12 weeks on treatment) occurred in 43% of patients on fostamatinib vs. 14% on placebo (P = .0006).
Median time to response was 15 days (on 100 mg bid), and 83% responded within 8 weeks. The most common adverse events were diarrhea (31% on fostamatinib vs. 15% on placebo), hypertension (28% vs. 13%), nausea (19% vs. 8%), dizziness (11% vs. 8%), and ALT increase (11% vs. 0%).
Most events were mild or moderate and resolved spontaneously or with medical management (antihypertensive, anti?motility agents). Fostamatinib produced clinically?meaningful responses in ITP patients including those who failed splenectomy, thrombopoietic agents, and/or rituximab. Fostamatinib is a novel ITP treatment option that targets an important mechanism of ITP pathogenesis.