Rilzabrutinib for persistent or chronic immune thrombocytopenia (ITP): a Bruton tyrosine kinase inhibitor that can target multiple pathophysiological pathways

INTRODUCTION: Immune thrombocytopenia (ITP) is characterized by reduced platelet production and platelet destruction. Despite the availability of numerous treatments, many patients develop treatment resistance, experience relapse, or suffer from persistent symptoms such as fatigue, highlighting the need for innovative immune-modulating techniques. This review highlights the chemical properties, clinical efficacy and safety evidence for rilzabrutinib. AREAS COVERED: Bruton tyrosine kinase (BTK) is a promising therapeutic target in ITP as it is essential for B-cell receptor signaling, Fcγ receptor-mediated platelet clearance, and inflammatory amplification. Rilzabrutinib is a reversible, covalent oral BTK inhibitor developed to treat immune-mediated disorders. It targets several pathogenic immunological pathways. In the phase 2 LUNA 2 trial and the subsequent randomized, placebo-controlled, phase 3 LUNA 3 study, rilzabrutinib was clinically evaluated in patients with persistent or chronic ITP. The treatment resulted in durable platelet responses in extensively pretreated patients, decreased bleeding episodes, and led to significant improvements in patient-reported fatigue. The safety profile was generally good with adverse events considered mild to moderate. EXPERT OPINION: The approval of rilzabrutinib for persistent and chronic ITP represents an important addition to the therapeutic armamentarium for the disease. The drug's full potential will be further defined in future studies.