Oral selective C5a receptor antagonist that blocks complement-mediated neutrophil activation — a key driver of ANCA-associated vasculitis.
Severe active ANCA-associated vasculitis (AAV) including Granulomatosis with Polyangiitis (GPA) and Microscopic Polyangiitis (MPA).
Used alongside rituximab or cyclophosphamide-based regimens as part of standard induction therapy for AAV.
Under active FDA & EMA safety review due to serious hepatotoxicity signals including fatal DILI and Vanishing Bile Duct Syndrome.
The most important new pharmacovigilance signal identified in 2026 — serious hepatotoxicity with fatal outcomes.
The FDA identified 76 post-marketing cases of drug-induced liver injury (DILI), including 74 serious cases, 54 hospitalizations, and 8 deaths. Multiple cases of Vanishing Bile Duct Syndrome (VBDS) were reported.
A rare but severe condition characterized by progressive destruction of intrahepatic bile ducts, leading to chronic cholestasis and irreversible liver damage.
Japan reported the highest concentration of fatal hepatic cases, prompting temporary prescription restrictions.
A major FAERS pharmacovigilance analysis published in 2025 identified disproportionate reporting signals beyond clinical trial observations.
| Adverse Drug Reaction | Severity | Source |
|---|---|---|
| Nausea | Mild–Moderate | Clinical Trial |
| Headache | Mild | Clinical Trial |
| Hypertension | Moderate | Clinical Trial |
| Elevated Liver Enzymes | Moderate–Severe | Both |
| Rash | Mild–Moderate | Clinical Trial |
| Fatigue | Mild | Clinical Trial |
| Diarrhea | Mild | Clinical Trial |
| Alopecia | Mild | Post-Marketing |
| Hearing Disorders | Moderate | Post-Marketing |
| Serious Infections / Sepsis | Severe | Both |
| Hepatitis | Severe | Post-Marketing |
| Vanishing Bile Duct Syndrome | ⚠ Potentially Fatal | Post-Marketing |
| Acute Liver Failure | ⚠ Potentially Fatal | Post-Marketing |
The FDA reportedly requested voluntary withdrawal of Tavneos from the U.S. market citing safety concerns, liver toxicity, and questions regarding ADVOCATE trial data adjudication. Amgen declined and continues discussions with regulators.
FDA issued a major Drug Safety Communication identifying 76 post-marketing DILI cases, 8 deaths, and multiple VBDS cases. Most reports originated from Japan.
The European Medicines Agency initiated an Article-20 safety review of Tavneos due to serious liver injury reports, fatal hepatotoxicity cases, and reassessment of the benefit-risk balance.
Japanese regulators temporarily restricted new prescriptions following ~20 fatal hepatic cases among ~8,500 exposed patients. Use was later resumed with stronger warnings and mandatory liver monitoring.
"Amgen declined the FDA's request for voluntary withdrawal and continues discussions with regulators regarding the benefit-risk profile of Tavneos in ANCA-associated vasculitis."
→ Amgen Official Statement (2026)Patients receiving avacopan require intensive hepatic surveillance throughout treatment.
| Benefit in AAV | Significant |
| Hepatic Safety Concern | High |
| FDA Safety Concern | Active |
| EMA Review | Ongoing |
| Major New ADR Signal | VBDS |
| Monitoring Requirement | Intensive LFT Monitoring |
| Overall PV Status | Under Close International Review |