US Data Links Vasculitis Drug Avacopan to Liver Injury

U.S. registry data has confirmed a link between the controversial vasculitis drug avacopan (Tavneos) and liver injury, adding to existing concerns that have prompted the U.S. Food and Drug Administration (FDA) to request its withdrawal from the market. The drug, approved in October 2021 by the FDA for the treatment of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), has faced scrutiny over its safety profile. The new study, published in the journal *Rheumatology*, analyzed data from the U.S. Vasculitis Registry, a comprehensive database tracking patients with vasculitis. Researchers identified a statistically significant association between avacopan use and elevated liver enzymes, a key indicator of liver damage. Specifically, the study found that patients treated with avacopan were more likely to experience alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels exceeding three times the upper limit of normal compared to those treated with standard immunosuppressive therapies. The FDA's concern stems from these findings, which align with earlier signals of potential hepatotoxicity. In a recent communication, the FDA informed Amgen, the drug's manufacturer, of its intention to seek a voluntary market withdrawal of Tavneos due to these safety concerns. The agency cited the increased risk of liver injury as the primary reason for this action. Amgen has not yet publicly responded to the FDA's request, but the company is expected to provide a formal statement in the coming weeks. Avacopan is a first-in-class selective C5a receptor inhibitor, designed to reduce inflammation associated with AAV by blocking the activity of the complement system. It was approved as an adjunctive therapy to standard of care, offering an alternative to prolonged high-dose glucocorticoids, which are associated with significant side effects. The potential for liver injury, however, presents a serious challenge to its continued use. The U.S. Vasculitis Registry, established in 2009, collects detailed clinical and laboratory data from patients diagnosed with various forms of vasculitis across multiple academic medical centers in the United States. Its aim is to improve understanding of disease pathogenesis, treatment outcomes, and long-term prognosis. The current analysis involved a cohort of over 2,000 patients diagnosed with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), the two most common forms of AAV. The study employed a retrospective cohort design, comparing outcomes between patients who received avacopan and a propensity score-matched control group. The findings underscore the importance of vigilant post-market surveillance for newly approved medications, particularly those targeting complex autoimmune conditions. Clinicians treating patients with AAV will need to carefully weigh the benefits of avacopan against the newly confirmed risks of liver injury, and monitor patients closely for any signs of hepatic dysfunction. The potential market withdrawal of avacopan could necessitate a return to or increased reliance on traditional glucocorticoid-based regimens, despite their known adverse effects. This situation highlights the ongoing challenges in developing safer and more effective treatments for rare and severe autoimmune diseases.