Expanding therapeutic options for patients with primary immune thrombocytopenia

Primary immune thrombocytopenia is an autoimmune disease associated with a reduced peripheral blood platelet count and complex underlying pathophysiology. Since spleen tyrosine kinase (Syk) is crucial in Fcγ receptor-mediated platelet phagocytosis, it was postulated that inhibition of Syk could be used as a possible mechanism to ameliorate disease activity. Syk inhibitors target not only antibody-sensing innate inflammatory cells, but also the activation of antibody-producing B lymphocytes, 1 Ackermann JA Nys J Schweighoffer E McCleary S Smithers N Tybulewicz VL Syk tyrosine kinase is critical for B cell antibody responses and memory B cell survival. J Immunol. 2015; 194: 4650-4656 Crossref PubMed Scopus (40) Google Scholar which might contribute to a more potent disruption of long-term memory antibody responses than approaches based on B lymphocyte depletion. Because Syk is also present in platelets, its inhibition confers the additional advantage of reducing thrombus formation. 2 Jooss NJ De Simone I Provenzale I et al. Role of platelet glycoprotein VI and tyrosine kinase Syk in thrombus formation on collagen-like surfaces. Int J Mol Sci. 2019; 202788 Crossref PubMed Scopus (25) Google Scholar Consequently, Syk has become a good novel target for the treatment of patients with primary immune thrombocytopenia. Sovleplenib (HMPL-523), a novel Syk inhibitor, for patients with primary immune thrombocytopenia in China: a randomised, double-blind, placebo-controlled, phase 1b/2 studySovleplenib was well tolerated, and the recommended phase 2 dose showed a promising durable response in patients with primary immune thrombocytopenia, which provides evidence for future investigations. A phase 3 trial is ongoing ( NCT05029635 ) to confirm the efficacy and safety of sovleplenib in patients with primary immune thrombocytopenia. Full-Text PDF