FDA Issues Alert on Liver Injuries Linked to Vasculitis Drug, Following Withdrawal Request

 US regulators issued a new alert about liver injury, including fatal cases, linked to avacopan (Tavneos), a medicine for a rare autoimmune disease that the agency had already asked to be voluntarily removed from the market.

The FDA on March 31 issued a public notice about serious postmarketing cases of drug-induced liver injury (DILI) associated with avacopan. The drug’s manufacturer, Amgen, announced in January that it intended to continue to market this drug even though the FDA requested a voluntary withdrawal of avacopan. Separately, European regulators in January announced a safety review of the drug.

In the new alert, the FDA recommended patients talk to their healthcare professional about safety risks associated with avacopan and discuss whether to continue therapy or switch to alternative treatments. In 2021, FDA staff expressed deep concern about liver risk even while approving avacopan for a serious and sometimes fatal autoimmune condition, severe active antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis. The FDA required a special safety study focused on liver risk as part of this approval.

The FDA’s alert urges people taking avacopan to contact their clinicians immediately if they develop any signs or symptoms of liver injury, including nausea, vomiting, unusual itching, light-colored stools, yellowing of skin or eyes, dark urine, swelling in the stomach or abdomen, or pain in the right upper abdomen.

The FDA also advised clinicians who have patients taking avacopan to conduct liver panel testing every 2 weeks in the first month of treatment, monthly for the next 5 months, and thereafter as clinically indicated. 

The FDA said avacopan should be discontinued promptly and alternative treatments should be considered if alanine aminotransferase (ALT) or aspartate aminotransferase (AST) is greater than three times the upper limit of normal or alkaline phosphatase (ALP) is greater than twice the upper limit of normal, as well as if a patient presents with evidence of symptomatic cholestasis such as jaundice or pruritus. If liver test abnormalities or symptoms of liver injury do not improve, patients should be referred to a hepatologist for further evaluation.

The FDA told clinicians to consult the American College of Rheumatology and Vasculitis Foundation’s 2021 treatment guidelines for ANCA-associated vasculitis for more information.

Amgen told Medscape Medical News in a March 31 email that the company remains confident that avacopan is an “important and effective” medicine for severe ANCA-associated vasculitis “based on robust clinical data and real-world evidence demonstrating the effectiveness and favorable benefit-risk profile.” 

The company said it remains committed to keeping the drug on the market. Amgen also said that in 2024 it submitted a proposed update to the FDA to add vanishing bile duct syndrome (VBDS) to avacopan’s label, a request that Amgen said is still pending.

The FDA’s March 31 alert says that the agency identified 76 cases of drug-induced liver injury (DILI) “with reasonable evidence of a causal association with avacopan use.” These come from reviews of postmarketing data, medical literature, and the FDA Adverse Event Reporting System, which is now called the FDA Adverse Event Monitoring System.

Of these 76 cases, 74 reported a serious outcome, including 54 hospitalizations and eight deaths, the FDA said. 

Sixty cases provided laboratory information to determine the initial pattern of liver injury, the FDA said. The majority (n = 38) had a cholestatic or mixed pattern often marked by substantial elevations in ALP and total bilirubin, the FDA said. VBDS confirmed by biopsy occurred in seven patients, all of whom were hospitalized and three of whom died. A total of 73 cases provided time from avacopan initiation to DILI onset, and the median time to onset was 46 days (range, 22-140 days). Most cases (n = 66) were reported from Japan, followed by the United States (n = 5), Europe (n = 4), and Canada (n = 1).

"The FDA's Drug Safety Communication about avacopan highlighting the eight fatal cases of drug-induced liver injury is important, but insufficient," Robert Steinbrook, MD, Health Research Group Director at the nonprofit watchdog group Public Citizen, told Medscape Medical News when asked for comment on the FDA's action.

"If the FDA in January 2026 requested that the drug be voluntarily withdrawn the drug from the US market, as Amgen has disclosed, why is the agency not making this request publicly, and pushing back against the company for not having already withdrawn the drug?" Steinbrook asked. "Why does the prescribing information for avacopan not include a boxed warning for the risk of fatal liver disease? These are urgent questions for the FDA to answer."

https://www.medscape.com/viewarticle/fda-issues-alert-liver-injuries-linked-vasculitis-drug-2026a10009tr