Avacopan C5a anaphylatoxin chemotactic receptor 1 (C5aR1) antagonist, Treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis

Inflammation is a key component of several clinically important disorders, with the recruitment of neutrophils often pivotal to the inflammatory process. Enzymatic activation of the complement cascade results in generation of the complement fragment C5a, a potent chemoattractant for neutrophils. C5a functions by binding to 2 specific G protein-coupled receptors named C5aR1 and C5aR2 on the surface of neutrophils and drives cell activation and migration. Avacopan (CCX-168) is a small molecule antagonist of C5aR1 which was developed by ChemoCentryx. Avacopan binds with nanomolar affinity to C5aR1 and is a potent inhibitor of neutrophil recruitment in vitro and in vivo. Avacopan appears to be well tolerated and in a phase III trial involving individuals with anti-neutrophil cytoplasmic antibody (ANCA)-induced vasculitis, blockade of C5aR1 by avacopan was reported to be efficacious in sparing high levels of glucocorticoid usage, providing a potential alternative protocol for the treatment of relapses.

Automated summary

Inflammation is a key component in various clinically important disorders, with neutrophil recruitment playing a crucial role. C5a is a potent chemoattractant for neutrophils, while Avacopan, a small molecule antagonist of C5aR1, inhibits neutrophil recruitment and shows potential efficacy in treating ANCA-induced vasculitis.