HUTCHMED (China) Limited announces that results from ESLIM-01, HUTCHMED?s Phase III trial of sovleplenib (HMPL-523), in adult patients with primary immune thrombocytopenia (?ITP?) in China, were published in The Lancet Haematology. Additional details and subgroup results of the study were also presented on June 14 at the European Hematology Association (?EHA?) 2024 Hybrid Congress as an oral and two poster presentations. Sovleplenib is a novel, selective, oral inhibitor targeting spleen tyrosine kinase (?Syk?) for the treatment of hematological malignancies and immune diseases.

Syk is a component in Fc receptor (?FcR?) and B-cell receptor signaling pathway. ITP is a complex autoimmune bleeding disorder, leading to a reduced platelet level in the peripheral blood. ITP can also impact on patients?

quality of life due to fatigue, restrictions on activities and anxiety. The ESLIM-01 trial results published by The Lancet Haematology suggest that sovleplenib could be a potential treatment option for patients with ITP who received at least one prior therapy. ESLIM-01 is a 2:1 randomized, double-blind, Phase III study conducted in 188 adult patients with primary ITP who had received at least one previous anti-ITP treatment (NCT05029635).

The study demonstrated a clinically meaningful early and sustained durable platelet response in patients with primary ITP, with a tolerable safety profile and improvement in quality of life. The primary endpoint was met, with durable response rate of 48.4% (61/126) with sovleplenib compared to zero with placebo (p<0.0001), which was consistent across most pre-defined subgroups. In addition, overall response rates were 68.3% at 0?12 weeks and 70.6% at 0?24 weeks with sovleplenib, compared to 14.5% and 16.1% with placebo (p<0.0001).

The median time to response was 8 days with sovleplenib compared to 30 days with placebo. Further post-hoc subgroup analysis of the study demonstrated consistent clinical benefits across ITP patients regardless of prior lines of ITP therapies or prior TPO/TPO-RA exposure, including TPO/TPO-RA treatment types and number of prior regimens. Most patients were heavily pretreated with a median of four prior lines of ITP therapy.

In patients who received four or more prior lines of therapy, the durable response rate was 47.7% with sovleplenib compared to 0% with placebo (p<0.0001). In addition, a majority of the patients had received prior TPO/TPO-RA. 74.6% of patients in the sovleplenib group had received prior treatment with TPO/TPO-RA, and analysis in this subgroup also demonstrated a significantly higher durable response rate of 46.8% with sovleplenib compared to zero with placebo (p<0.0001).

The safety profile of sovleplenib in ESLIM-01 was consistent with previously reported studies. The majority of treatment-emergent adverse events (?TEAEs?) were mild or moderate in severity (grade 1 or 2). Grade 3 or above TEAEs were reported in 25.4% of patients with sovleplenib and 24.2% with placebo.

Sovleplenib also significantly improved quality of life in physical functioning and energy/fatigue (p<0.05).2 The China National Medical Products Administration (?NMPA?) granted Breakthrough Therapy designation for this indication and accepted the New Drug Application (?NDA?) for review with Priority Review in January 2024. A dose-finding study in the U.S. is being planned (NCT06291415). HUTCHMED also initiated the registration stage of the Phase II/III clinical trial of sovleplenib in adult patients with warm antibody autoimmune hemolytic anemia (?wAIHA?) in China in March 2024 (NCT05535933).

HUTCHMED retains all rights to sovleplenib worldwide.