U.S. Registry Data Confirm Liver Risk With Controversial Vasculitis Drug

A new study reveals potential liver risks associated with the controversial vasculitis drug avacopan (Tavneos), which was approved in 2021 by the FDA for treating ANCA-associated vasculitis (AAV). Of the 238 patients in a U.S. rheumatology registry who received avacopan for AAV, 14 instances of clinically significant liver enzyme elevations were recorded among 10 patients, and two patients experienced drug-induced liver injury (DILI) likely caused by avacopan, according to researchers Eric T. Roberts, PhD, MPH, and colleagues from the University of California San Francisco.

One of the DILI cases was severe, but neither the severe nor the less severe case resulted in vanishing bile duct syndrome (VBDS).

Avacopan, an oral C5a complement inhibitor, generated $459 million in global sales for Amgen in 2021. However, the drug is now embroiled in controversy following the FDA's January 2026 warning of liver risks beyond the initial hepatotoxicity warning listed in the drug's label. The FDA also questioned the data integrity of the ADVOCATE trial supporting avacopan's approval and ordered Amgen to remove avacopan from the market. In March, the FDA reported eight deaths linked to avacopan and dozens of nonfatal DILI cases.

Another complication emerged in June when the New England Journal of Medicine retracted the ADVOCATE trial's results due to altered data post-unblinding, purportedly by ChemoCentryx, the company that developed avacopan before selling its U.S. rights to Amgen. Despite these setbacks, Amgen has refused to withdraw avacopan from the U.S. market, while the European Union revoked its authorization earlier this month.

The new report, using data from the American College of Rheumatology's RISE registry, adds fuel to the controversy by presenting U.S. clinicians' relatively infrequent liver testing practices. Liver enzyme elevations were identified using FDA's standard definitions and bilirubin elevations as a marker, with patients having at least two enzymes elevated then evaluated for DILI.

Of the eight DILI cases, two were severe, both involving middle-aged women with the granulomatosis-with-polyangiitis subtype of AAV, and neither progressed to VBDS. The study suggests that liver testing should be performed frequently during the first three months of avacopan use, as recommended by the FDA.