HUTCHMED Initiates a Phase 2/3 Trial of Sovleplenib for Warm Antibody Autoimmune Hemolytic Anemia

HUTCHMED (China) Limited recently announced it has initiated a Phase 2/3 trial of sovleplenib in adult patients with warm antibody autoimmune hemolytic anemia (wAIHA) in China. wAIHA is an autoimmune disorder that can lead to anemia and has limited treatment options. The first patient received the first dose on September 30, 2022.

This is a randomized, double blind, placebo-controlled clinical trial. The Phase 2 stage of the study is to evaluate the safety and preliminary efficacy of sovleplenib in adult patients with wAIHA. If results of the Phase 2 stage are positive, the Phase 3 stage will be initiated to confirm such efficacy and safety. The primary endpoint for the Phase 2 study is the proportion of patients with overall hemoglobin (Hb) response by Week 24, whereas the primary endpoint for the Phase 3 study would be the proportion of patients who achieve a durable Hb response by Week 24. Approximately 110 patients are expected to be enrolled. The lead principal investigators are Dr. Liansheng Zhang of Lanzhou University Second Hospital, Dr. Fengkui Zhang of Chinese Academy of Medical Sciences Blood Diseases Hospital and Dr. Bing Han of Chinese Academy of Medical Sciences Peking Union Medical College Hospital. Additional details may be found at clinicaltrials.gov, using identifier NCT05535933.

Sovleplenib is a novel, investigational, selective small molecule inhibitor for oral administration targeting the spleen tyrosine kinase, also known as Syk. Syk is a major component in B-cell receptor and Fc receptor signaling and is an established target for the treatment of multiple subtypes of B-cell lymphomas and autoimmune disorders.

HUTCHMED currently retains all rights to sovleplenib worldwide. In addition to wAIHA, sovleplenib is also being studied in immune thrombocytopenia (NCT05029635), indolent non-Hodgkin’s lymphoma and multiple subtypes of B-cell malignancies in China, the U.S. and Europe (NCT02857998; NCT03779113).

AIHA is an autoimmune disorder characterized by the destruction of red blood cells (“RBCs”) due to the production of antibodies against RBC. The incidence of AIHA is estimated to be 0.8-3.0/100,000 adults per year with an estimated prevalence of 17 per 100,000 adults and a death rate of 8%-11%. wAIHA is the most common of the autoimmune hemolytic diseases, accounting for about 75%-80% of all adult AIHA cases.

The accelerated clearance of antibody-coated RBCs by immunoglobulin Fc receptor (FcR) bearing macrophages is thought to be the pathogenic mechanism in wAIHA. Activation of the FcR is associated with a signaling subunit, FcRγ, whose phosphorylation subsequent to receptor binding results in the recruitment and activation of Syk. Activated Syk mediates downstream signaling of the activated FcRs in phagocytic cells, resulting in phagocytosis of RBCs. In addition, activation of Syk through the B-cell receptor mediates activation and differentiation of B-lymphocytes into antibody secreting plasma cells. Therefore, inhibition of Syk may have potential effects in the treatment of wAIHA through inhibition of phagocytosis and reduction of antibody production.

HUTCHMED is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has more than 4,900 personnel across all its companies, at the center of which is a team of over 1,800 in oncology/immunology. Since inception it has advanced 13 cancer drug candidates from in-house discovery into clinical studies around the world, with its first three oncology drugs now approved and marketed in China. For more information, visit www.hutch-med.com.