FDA proposes withdrawal of avacopan (TAVNEOS) approval after identifying lack of efficacy evidence, data manipulation in the pivotal ADVOCATE trial, and emerging safety concerns including hepatotoxicity.
Written By: Samiksha Jadhav, BPharm
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration (FDA) has proposed withdrawal of marketing approval for avacopan (TAVNEOS), a complement C5a receptor inhibitor approved in 2021 as an adjunctive treatment for adult patients with severe active ANCA‑associated vasculitis (AAV).
The action follows following FDA concerns that the approval was based on unreliable results from the Phase 3 ADVOCATE trial, which was the sole pivotal study supporting the drug’s authorization.
In the original pre‑specified analysis after the first database lock in November 2019, avacopan did not demonstrate statistically superior sustained remission at 52 weeks compared with standard therapy. After unblinding, sponsor personnel selected a subset of patients for readjudication, reclassifying outcomes which resulted in the study outcome changing from non-significant to statistically significant, without disclosing the earlier negative analysis or the post‑unblinding changes.
The FDA concluded that this process introduced bias, violated good clinical practice, and undermined the reliability of the efficacy findings, leaving only the original non‑significant result as interpretable.
The agency also determined that the FDA determined that the new drug application contained untrue statements of material fact, including failure to disclose multiple database locks, unblinding events, and altered analyses that materially affected the benefit‑risk assessment.
In addition, postmarketing safety data have identified 76 cases of drug‑induced liver injury associated with avacopan, 74 of which were serious and included hospitalizations and deaths; seven patients developed biopsy‑confirmed vanishing bile duct syndrome. With no confirmed clinical benefit and these serious, sometimes fatal hepatic risks, the FDA considers the drug’s benefit‑risk profile unfavorable.
On March 31, 2026, the FDA already flagged serious and potentially fatal liver injury, including cases of vanishing bile duct syndrome (VBDS), associated with Tavneos (avacopan).
Based on these findings, the FDA has initiated formal proceedings under section 505(e)(3) of the FD&C Act to withdraw approval of avacopan, while providing the sponsor an opportunity for a hearing. If the withdrawal is finalized, avacopan will no longer be permitted for marketing in the United States.
TAVNEOS will remain available in the U.S. market until either the applicant voluntarily removes it or the FDA Commissioner orders its removal. If the applicant requests a hearing, the FDA Commissioner will decide whether to hold a public hearing and, after the hearing, determine whether to withdraw approval of TAVNEOS.
Until a final decision is reached, health care professionals are advised to discuss TAVNEOS and other available treatment options with their patients to decide whether to initiate or continue therapy.
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About the Writer
Samiksha Vikram Jadhav is a B. Pharm graduate with a strong academic foundation in pharmaceutical sciences, pharmacology, and drug development. She specializes in pharma market research, with a focused interest in mergers and acquisitions, strategic partnerships, and global pharma and biotech deals. Her work centers on analyzing industry transactions, market positioning, and business strategies, translating complex developments into clear, accurate, and insightful scientific and commercial reporting.