Phase 2 Data Available: Spleen Tyrosine Kinase Inhibitor for Warm Autoimmune Hemolytic Anemia

A phase 2/3 study for preliminary evaluation of sovleplenib, an oral spleen tyrosine kinase inhibitor, for treatment for warm autoimmune hemolytic anemia is under way. Results from the study’s phase 2, randomized, double-blind, placebo-controlled component are published in The Lancet Haematology.

“Sovleplenib treatment achieved an encouraging overall haemoglobin response in Chinese patients with warm autoimmune haemolytic anaemia and was well tolerated,” wrote first author Xin Zhao, MD, of the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin, and colleagues.

The phase 2 component was conducted at 13 medical centers with patients who had primary or secondary warm autoimmune hemolytic anemia, a hemoglobin concentration of less than 100 g/L, active hemolysis, and a positive direct antiglobulin test result. Previous glucocorticoid therapy had been ineffective in these patients.

The enrolled cohort comprised 21 patients (4 men and 17 women) aged 18 to 75 years. Sixteen patients were randomized to receive oral sovleplenib and 5 received placebo 300 mg once a day for an 8-week double-blind treatment period. All patients then proceeded to an open-label treatment period during which they received sovleplenib 300 mg once a day for at least 16 weeks, until 24 weeks after the last patient had been assigned to a treatment group.

To measure efficacy in the patients, overall hemoglobin response was defined as a hemoglobin concentration of 100 g/L or greater by week 24 with at least one increase of 20 g/L or greater from baseline and no effect on hemoglobin from any rescue therapy. By week 24 among all 21 patients, the rate of overall hemoglobin response was 67%, and the rate of durable hemoglobin response was 48%.

Regarding safety results during the 8-week double-blind treatment period, treatment-emergent adverse events (TEAEs) affected 81% of the patients who received sovleplenib versus 100% of patients who received placebo. Grade 3 events were reported by 25% of patients who received sovleplenib and 80% of patients who received placebo.

During the 24-week open-label treatment period with sovleplenib, 100% of patients experienced at least one TEAE, 33% experienced grade 3 events, and none had grade 4 or 5 TEAEs. Treatment-unrelated anemia was the most common grade 3 TEAE, having occurred in 19% of patients.

The phase 2/3 study is funded by HUTCHMED.

Reference

Zhao X, Sun J, Zhang Z, et al. Sovleplenib in patients with primary or secondary warm autoimmune haemolytic anaemia: results from phase 2 of a randomised, double-blind, placebo-controlled, phase 2/3 study. Lancet Haematol. 2025;12(2):e97-e108. doi:10.1016/S2352-3026(24)00344-2