Retracted Trial Publication Undermines Support for Avacopan in AAV Treatment

The Retracted Trial Publication of the ADVOCATE study has eliminated the central evidence that supported approval of Tavneos (avacopan) for severe active anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV). At the request of two lead academic authors, the New England Journal of Medicine withdrew the 2021 paper after an FDA investigation uncovered undisclosed post-unblinding changes to primary endpoint data.

Endpoint Integrity Breached

Outcome assessments for nine participants were readjudicated after database lock and trial unblinding, alterations never disclosed in the original manuscript. This Retracted Trial Publication exposed deviations that regulators determined violated good clinical practice and undermined the reliability of the remission claims used for approval.

Liver Toxicity Converges with Data Concerns

Post-marketing reports have linked avacopan to 76 cases of drug-induced liver injury, including 54 hospitalizations and eight deaths. These safety signals, paired with the Retracted Trial Publication, prompted the FDA to propose rescinding approval and the EMA’s CHMP to recommend full revocation of marketing authorization.

Market Access at Risk

Amgen, which acquired the original sponsor for $3.7 billion in 2022, is now performing an independent blinded re-adjudication through the Duke Clinical Research Institute, with results due by July 29, 2026. The episode demonstrates how quickly payer and HTA confidence can erode for orphan autoimmune therapies once foundational evidence is retracted, even after annual revenues approached $459 million.