Liver Injury Risks Tied to Avacopan
A new analysis of U.S. patient records links the drug avacopan to liver injury, adding pressure on manufacturer Amgen. Avacopan, branded as Tavneos, received regulatory clearance in 2021 to treat anti-neutrophil cytoplasmic autoantibody-associated vasculitis. Researchers examining data from 238 patients in a major rheumatology registry identified two cases of drug-induced liver injury and 14 instances of significant liver enzyme elevations.
The findings appeared Monday in the journal Arthritis & Rheumatology. Eric T. Roberts, PhD, MPH, of the University of California San Francisco, led the team that reviewed these cases. One patient suffered severe liver injury, while the other case was less extreme. Both patients required roughly two months to recover after they stopped taking the medication. Neither patient developed the life-threatening vanishing bile duct syndrome.
Regulatory Pressure and Data Integrity Issues
Avacopan is now the center of a mounting regulatory storm. The FDA stated earlier this year that it identified liver risks exceeding the warnings already printed on the drug label. Officials have reported dozens of nonfatal cases and eight fatalities linked to the drug. Beyond these safety concerns, the FDA has questioned the integrity of the clinical data used to support the original approval of the drug in the ADVOCATE trial.
In June, the New England Journal of Medicine retracted the paper that detailed the ADVOCATE trial findings. Academic authors requested this retraction after discovering that data had been altered post-unblinding, reportedly by employees of ChemoCentryx, the company that originally developed the drug. Amgen continues to sell the drug in the United States, although the European Union revoked its authorization earlier this month.
Screening Deficiencies in Clinical Practice
The study highlights a gap between recommended safety protocols and actual clinical behavior. The FDA advises that providers administer liver panels every two weeks during the first month of treatment and monthly thereafter until month six. Roberts and his team found that clinicians waited a median of 32 days for the first test. Many providers allowed testing intervals to stretch beyond six months.
Researchers noted that the frequency of enzyme elevations observed in this registry was similar to what is seen with methotrexate. However, overt drug-induced liver injury occurs far less frequently with methotrexate than what this data indicates for avacopan. Clinicians now face pressure to improve monitoring frequency to mitigate potential harm. The authors of the study maintain that while the drug remains a therapeutic option, providers must ensure patients understand the risks and strictly follow monitoring schedules during the first 90 days.