A Post-Marketing Evaluation of Avacopan Safety with a Focus on Hepatic Adverse Events

Background: Avacopan, an oral complement C5a receptor inhibitor, has been shown to help patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) achieve and sustain remission with reduced glucocorticoid exposure and associated toxicity. As of January 20, 2026, estimated global post-marketing exposure exceeded 25,000 patient-years. Hepatic adverse events (AEs), predominantly liver enzyme elevations observed during clinical development, remain an important post approval safety risk. Since approval, vanishing bile duct syndrome (VBDS), a rare but serious complication of drug induced liver injury (DILI) has been reported with avacopan use. This analysis evaluated Amgen's global safety database data to characterize hepatic adverse event reports associated with avacopan, including VBDS. Methods: We conducted a retrospective descriptive analysis of hepatic AEs recorded in the Amgen global safety database. Results: As of 20 January 2026, serious hepatic AEs were reported at approximately 31 events/1,000 patient-years. The majority of hepatic events comprised laboratory abnormalities that resolved following avacopan discontinuation. Thirty-one VBDS cases were reported and, of those, 27 originated from Japan. Fatal VBDS cases were reported predominantly from Japan and occurred in patients >65 years. Conclusions: Hepatotoxicity remains an important avacopan-specific safety risk. Post-marketing data indicate that most hepatic events are reversible laboratory abnormalities; however, serious liver injury and VBDS, including fatal outcomes, have been reported, predominantly from Japan. No new safety risks have emerged from the ongoing Japanese post-marketing study. Further investigation is warranted to understand potential mechanisms underlying the disproportionate occurrence of serious VBDS events in Japanese patients and inform optimized risk-mitigation strategies.