Recent U.S. registry data comprising 238 patients treated with the C5a complement inhibitor avacopan identified 14 instances of significant liver enzyme elevations and two cases of drug-induced liver injury, according to a study published in Arthritis & Rheumatology by Eric T. Roberts, PhD, MPH, of the University of California San Francisco, and colleagues. The findings add to growing regulatory scrutiny surrounding the medication, which the FDA previously told drugmaker Amgen to remove from the U.S. market following safety analyses identifying multiple fatalities and data integrity questions in foundational clinical trials.
Liver Injury Findings in U.S. Registry Data
The analysis evaluated patients in the American College of Rheumatology’s RISE registry who received avacopan for anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis between October 2021 and March 2025. According to Roberts and colleagues, two middle-aged women with the granulomatosis-with-polyangiitis subtype developed drug-induced liver injury after nine weeks of treatment. Both cases yielded RUCAM scores of 9, indicating a high likelihood that avacopan caused the hepatotoxicity. Neither patient progressed to vanishing bile duct syndrome, and both recovered within two months of stopping the medication.
Regulatory Pressure and Clinical Trial Controversy
Avacopan, marketed as Tavneos, generated global sales of approximately $459 million for Amgen last year, but the drug faces mounting international pressure. In February, the FDA stated it identified liver risks surpassing the product’s existing warning label and raised data integrity questions regarding the principal randomized trial, known as ADVOCATE. The agency reported eight deaths from liver injury and dozens of nonfatal cases linked to the drug. By June, the New England Journal of Medicine retracted the ADVOCATE trial results after academic authors discovered data modifications made after unblinding by personnel tied to developer ChemoCentryx.
Did you know? The European Union revoked authorization for avacopan earlier this month, though Amgen has declined to voluntarily withdraw the drug from the U.S. market in the absence of a mandatory federal order.
Monitoring Gaps in Routine Clinical Practice
The study also evaluated how closely U.S. rheumatologists adhered to recommended safety monitoring schedules. Researchers discovered that liver testing occurred at a median of 32 days after starting avacopan, with subsequent tests spaced at a median interval of 125 days. Data showed that one-quarter of clinicians waited longer than two months for an initial test, while another quarter allowed more than six months between subsequent evaluations. The study authors observed that these timelines fall short of FDA recommendations, which advise liver panels every two weeks during the first month and monthly through month six.
Frequently Asked Questions
What condition does avacopan treat?
Avacopan is an oral C5a complement inhibitor approved in 2021 to treat anti-neutrophil cytoplasmic autoantibody-associated vasculitis.
What are the primary liver risks associated with the drug?
The FDA and recent registry studies have identified risks of clinically significant liver enzyme elevations and drug-induced liver injury, including several reported fatalities.
How frequently should liver function be monitored during avacopan treatment?
According to federal guidance cited in the research, liver panels should be administered every two weeks during the first month of treatment and monthly through the first six months.
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