Phase 3 Outcomes of Fostamatinib for Patients With wAIHA

Fostamatinib, an oral spleen tyrosine kinase inhibitor approved for adults with chronic immune thrombocytopenia (ITP), yielded “a clinically meaningful benefit for patients [with warm antibody autoimmune hemolytic anemia (wAIHA)] in Western regions, and no new safety signals were identified,” according to the phase III FORWARD study.

The data were reported in the American Journal of Hematology by lead author, David Kuter, MD, of the Massachusetts General Hospital at Harvard Medical School in Boston. Dr. Kuter and colleagues noted there are no approved treatment options for patients with wAIHA, a burdensome condition characterized by hemolysis and symptomatic anemia.

The primary endpoint was proportion of patients who achieved a durable hemoglobin (Hgb) response, defined as Hgb ≥10 g/dL plus an increase from baseline levels of ≥2 g/dL on three consecutive visits over the 24-week study period.

Fostamatinib Separates From Placebo After Adjusted Analyses

FORWARD enrolled 90 patients with insufficient response to at least one prior treatment and randomly assigned 45 each to either fostamatinib or placebo. In the fostamatinib group, 35.6% of patients achieved a durable Hgb response compared with 26.7% in the placebo group (P=.398).

The report noted a post hoc analysis localized the large placebo response to Eastern European patients and qualified that the primary endpoint was achieved significantly more frequently with fostamatinib compared with placebo in patients from North America, Australia, and Western Europe (36.0% vs 10.7%; P=.030).

After adjusting for Hgb values that were affected by steroid rescue therapy during screening and excluding two placebo patients deemed not likely to have wAIHA, a follow-up analysis showed a significant difference (P=.0395) in inducing durable Hgb responses with fostamatinib (n=15; 33.3%) versus placebo (n=6; 14.0%).

Adverse events (AEs) occurred in 42 (93.3%) fostamatinib patients and 40 (88.9%) placebo patients, with the most common AEs in the fostamatinib group being diarrhea (26.7%), hypertension (24.4%), and fatigue (15.6%).

Overall, “the results presented here provide encouraging data that fostamatinib may induce durable Hgb responses that continue to build over time with a safety profile consistent with that of long-term studies in ITP and rheumatoid arthritis,” Dr. Kuter and colleagues summarized.

Reference

Kuter DJ, Piatek C, Röth A, et al. Fostamatinib for warm antibody autoimmune hemolytic anemia: phase 3, randomized, double-blind, placebo-controlled, global study (FORWARD). Am J Hematol. 2023. doi:10.1002/ajh.27144

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