The U.S. Food and Drug Administration (FDA) issued a Drug Safety Communication on 31 March 2026, alerting healthcare professionals and patients to serious cases of drug-induced liver injury (DILI) in postmarketing surveillance of avacopan — including cases with fatal outcomes.

While the FDA operates outside the European regulatory framework, its postmarketing findings are directly relevant to the EMA’s ongoing assessment.

The FDA identified 76 cases of DILI with a reasonable causal association with avacopan use. Of these, 74 had a serious outcome, including 54 hospitalisations and 8 deaths. A particularly concerning subset of 7 cases involved biopsy-confirmed vanishing bile duct syndrome (VBDS) — a progressive and potentially irreversible destruction of the bile ducts — of which 3 were fatal. The median time from starting avacopan to onset of liver injury was 46 days (range:22–140 days).

The geographical distribution is noteworthy: 66 of the 76 cases were reported from Japan, where avacopan has been prescribed far more widely than in Europe and where there is a higher background rate of liver toxicity. Four cases were reported from Europe.  This context matters, but does not diminish the seriousness of the signal.

Hepatotoxicity (liver damage caused by the medication) was already listed as a known adverse reaction in the product labelling based on the ADVOCATE trial. What is new is the occurrence of VBDS and fatal DILI outcomes in the real-world postmarketing setting — a finding that goes beyond what was observed in the controlled trial environment