Remibrutinib (Rhapsido®), a covalent Bruton’s tyrosine kinase inhibitor approved for chronic spontaneous urticaria

Abstract Remibrutinib (Rhapsido ® ) is a selective, orally bioavailable covalent inhibitor of Bruton’s tyrosine kinase (BTK), approved in 2025 for the treatment of adult chronic spontaneous urticaria (CSU) uncontrolled by H 1 -antihistamines. By blocking BTK, it suppresses signaling pathways driving mast cell, basophil, and B-cell activation in immune-mediated disease. This review traces remibrutinib’s journey from target validation to market approval, detailing the structure–activity relationships that optimized early CGI-560 and CGI-1746 scaffolds into pyrrolopyrimidine and 6-aminopyrimidine series, as well as the process chemistry redesign for commercial synthesis. By covalently capturing BTK in its inactive conformation, remibrutinib achieves exceptional kinase selectivity. This translates into rapid symptom control, convenient oral administration as an alternative to injectable biologics, and a favorable safety profile where mild mucocutaneous bleeding is the primary mechanism-based risk. Remibrutinib is also in late-stage development for other chronic, non-lethal inflammatory conditions including chronic inducible urticaria, hidradenitis suppurativa, Sjögren disease, and multiple sclerosis.