FDA Identifies Cases of Serious Liver Injury in Patients Taking Tavneo

After reviewing postmarketing data from the applicant’s submission (cases from their global safety database), the literature, and the FDA Adverse Event Reporting System (FAERS) database, which has been incorporated into the FDA Adverse Event Monitoring System (AEMS) database, through October 9, 2024, FDA identified 76 cases of DILI with reasonable evidence of a causal association with avacopan use. A total of 74 cases reported a serious outcome, including hospitalization (n=54) and death (n=8). A total of 60 cases provided laboratory information to determine the initial pattern of liver injury; the majority (n=38) had a cholestatic or mixed pattern often marked by substantial elevations in ALP and total bilirubin. A total of 73 cases provided time from avacopan initiation to DILI onset, and the median time-to-onset was 46 days (range 22 to 140 days). Most cases (n=66) were reported from Japan, followed by the United States (n=5), Europe (n=4), and Canada (n=1). 

Of the 76 cases, 7 reported biopsy-confirmed VBDS as a complication of DILI with reasonable evidence of a causal association with avacopan use. All cases reported hospitalization (n=7), of which 3 had a fatal outcome. The initial pattern of liver injury was cholestatic or mixed in 4 cases and hepatocellular in 3 cases. The median time from avacopan initiation to DILI onset among the 7 cases was 46 days (range 33 to 59 days). Cases were reported from Japan (n=6) and Canada (n=1). 

FDA is continuing to monitor postmarketing cases of DILI, including VBDS, involving avacopan and will provide updates as appropriate. 

Source