Sovleplenib Demonstrates Clinically Meaningful Response Among Patients With Chronic Primary Immune Thrombocytopenia

Results from the ESLIM-01 Trial

According to results from a phase 3 study, sovleplenib, a novel spleen tyrosine kinase inhibitor, demonstrated a clinically meaningful, sustained platelet response among patients with chronic primary immune thrombocytopenia, which included a tolerable safety profile and improvement in quality of life.

Previously recorded data exhibited that “sovleplenib showed promising safety and activity in patients with primary immune thrombocytopenia in a phase 1b/2 trial,” stated lead study author Yu Hu, MD, Union Hospital, Tongji Medical College Wuhan, China, and colleagues.

This randomized, double-blind, placebo-controlled, phase 3 trial was completed across 34 clinical centers in China. Eligible patients included those aged 18 to 75 years who had chronic primary immune thrombocytopenia, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, and received 1 or more previous treatments. Patients were randomly assigned on a 2-to-1 basis to receive oral sovleplenib or placebo, 300 mg once daily, for 24 weeks. Furthermore, randomization was stratified by baseline platelet counts, previous splenectomy, and concomitant treatment for anti-immune thrombocytopenia at baseline. Study authors noted the primary end point was durable response rate (proportion of patients with a platelet count of ≥50 × 10⁹/L on at least 4 of 6 scheduled visits between weeks 14 and 24, not affected by rescue treatment) assessed by intention-to-treat.

Between September 29, 2021, and December 31, 2022, 188 patients were randomly assigned to receive sovleplenib (n = 126) or placebo (n = 62). The median previous lines of immune thrombocytopenia therapy were 4 and 134 (71%) of 188 patients had received previous thrombopoietin or thrombopoietin receptor agonist. Study results demonstrated the primary end point was met. The durable response rate was 48% (61 of 126) with sovleplenib compared with 0 with placebo (difference 48% [95% [confidence interval] CI, 40 to 57]; P <0.0001). The median time to response was 8 days with sovleplenib, compared with 30 days with placebo.

Safety results showed that 125 (99%) of 126 patients in the sovleplenib group and 53 (85%) of 62 in the placebo group reported treatment-emergent adverse events, with most events being mild or moderate. Frequent treatment-emergent adverse events of grade 3 or higher for sovleplenib versus placebo were platelet count decreased (7% [9 of 126] versus 10% [6 of 62]), neutrophil count decreased (3% [4 of 126] versus 0% [0 of 62]), and hypertension (3% [4 of 126] versus 0% [0 of 62]). Incidences of serious adverse events were 21% (26 of 126) in the sovleplenib group and 18% (11 of 62) in the placebo group. No deaths occurred in this study.

“Sovleplenib showed a clinically meaningful sustained platelet response in patients with chronic primary immune thrombocytopenia, with a tolerable safety profile and improvement in quality of life,” concluded Dr Hu and colleagues.

“Sovleplenib could be a potential treatment option for patients with immune thrombocytopenia who received [1] or more previous therapy,” they added.

Source:

Hu Y, Liu X, Zhou H, et al. Efficacy and safety of sovleplenib (HMPL-523) in adult patients with chronic primary immune thrombocytopenia in China (ESLIM-01): a randomized, double-blind, placebo-controlled, phase 3 study. Published online June 14, 2024. doi: 10.1016/S2352-3026(24)00139-X