Avacopan Safety Concerns Grow Amid Liver Injury Signals, reports US registry analysis
USA: A new U.S. registry analysis involving more than 200 patients treated with avacopan (Tavneos) identified two cases of drug-induced liver injury (DILI), including one severe case, and 14 significant liver-enzyme elevations, adding to concerns about the drug’s hepatic safety.
Avacopan, approved by the FDA in 2021 for ANCA-associated vasculitis, has faced additional scrutiny over the integrity of data supporting its approval. In March 2026, the FDA reported 76 postmarketing cases of DILI, including 8 deaths and 7 cases of vanishing bile duct syndrome (VBDS), three of which were fatal.
The emerging evidence has intensified regulatory debate over Tavneos in the U.S., while highlighting the need for close liver-function monitoring and prompt discontinuation when significant liver injury develops.
The findings, published in Arthritis & Rheumatology by Eric T. Roberts of the University of Michigan, Ann Arbor, Michigan, US, and colleagues, provide real-world estimates of hepatic complications among patients receiving avacopan for ANCA-associated vasculitis (AAV).
Avacopan is an oral C5a receptor inhibitor used to reduce the need for prolonged glucocorticoid therapy in AAV. To assess its hepatic safety in routine clinical practice, researchers analyzed data from the Rheumatology Informatics System for Effectiveness Registry. The study included patients with AAV who received at least one avacopan prescription between October 2021 and March 2025.
A total of 238 patients were treated with the drug. Researchers assessed liver tests according to FDA-defined thresholds, including AST or ALT levels more than three times the upper limit of normal (ULN), alkaline phosphatase more than twice the ULN, or total bilirubin above 2 mg/dL.
The key findings were as follows:
- Five patients developed elevated AST, three had elevated ALT, four had increased alkaline phosphatase, and two had elevated total bilirubin.
- Incidence rates per 100 person-years were 4.24 for AST, 2.67 for ALT, 3.56 for alkaline phosphatase, and 1.80 for bilirubin.
- Two patients (0.8%) developed drug-induced liver injury (DILI) during avacopan treatment.
- Both DILI cases had a RUCAM score of 9, indicating a highly probable association with avacopan.
- One patient developed severe hepatocellular injury, which was confirmed by liver biopsy.
- The median time to the first liver-enzyme test after starting avacopan was 32 days, while subsequent testing occurred at an average interval of 125 days.
The researchers concluded that although clinically significant liver-enzyme elevations were uncommon in this real-world U.S. cohort, severe DILI can occur during avacopan therapy. They emphasized early and vigilant liver-function monitoring and careful discussion of hepatic risks with patients as regulatory authorities continue reassessing the drug's safety profile.
Reference:
Roberts, E. T., Dadabhoy, D., Antolini, R., Chung, S. A., Schmajuk, G., & Yazdany, J. Hepatotoxicity of Avacopan: Real-World Incidence and Confirmed Cases of Severe Drug-Induced Liver Injury in a US National Rheumatology Registry. Arthritis & Rheumatology. https://doi.org/10.1002/art.70304
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