Global Scrutiny Intensifies Over Amgen’s Rare-Disease Drug Tavneos Following Reports of Liver Injuries and Deaths in Japan

TOKYO — A wave of severe safety disclosures has placed a prominent rare-disease medication under intense global scrutiny. At least 20 patients in Japan have died after taking Amgen’s Tavneos (avacopan), and at least 22 others have developed potentially fatal liver injuries.

The findings, disclosed by Amgen’s Japanese marketing partner, Kissei Pharmaceutical, and initially reported by The Wall Street Journal, have altered the drug’s global risk profile. In response to the data, Kissei has urged physicians across Japan to stop initiating new patients on the therapy while regulatory authorities conduct a comprehensive review.

What the New Data Show

According to recent disclosures submitted to Japanese health authorities, Kissei Pharmaceutical confirmed that 20 patient deaths have been associated with Tavneos, which is prescribed for certain rare autoimmune vascular conditions. Additionally, at least 22 patients experienced severe liver-related harm. This includes confirmed cases of drug-induced liver injury (DILI) and vanishing bile duct syndrome (VBDS)—a severe, rare condition where the liver’s bile ducts are destroyed, frequently resulting in permanent organ damage or irreversible cirrhosis.

The surge in Japanese cases follows a March 2026 safety alert from the U.S. Food and Drug Administration (FDA). That alert identified 76 global reports of liver injury linked to Tavneos, including 54 hospitalizations and eight deaths. Japan accounts for the clear majority of these severe outcomes, demonstrating how post-marketing surveillance within a single nation can shift the safety profile of a globally distributed medication.

The Drug and its Original Promise

Tavneos (avacopan) is an oral, first-in-class therapy approved in the United States, the European Union, and Japan. It targets severe, active anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). AAV is a group of rare, life-threatening autoimmune diseases characterized by the inflammation of small- to medium-sized blood vessels, which can lead to catastrophic damage in vital organs like the kidneys and lungs. Specifically, the drug was authorized in Japan for two major forms of the condition: granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).

ANCA-Associated Vasculitis (AAV) 
  ├── Granulomatosis with polyangiitis (GPA)  --> Treated with Tavneos
  └── Microscopic polyangiitis (MPA)         --> Treated with Tavneos

In its pivotal Phase III ADVOCATE clinical trial, Tavneos was added to standard immunosuppressive regimens. The data revealed that the drug allowed many patients to significantly reduce or entirely avoid high-dose corticosteroids. Because long-term steroid use carries profound health risks—including diabetes, osteoporosis, and severe infections—regulatory bodies and patient advocacy groups initially heralded Tavneos as a major therapeutic breakthrough.

Growing Safety Concerns and Regulatory Friction

The safety profile of Tavneos has shifted significantly since its launch. The FDA’s March 2026 safety alert cited “reasonable evidence” of a causal link between avacopan and 76 cases of drug-induced liver injury. The timeline raised immediate concerns: the median time from the initiation of Tavneos to the onset of liver injury was just 46 days, meaning severe harm can develop early in the course of treatment.

Of particular concern were seven cases of vanishing bile duct syndrome, three of which resulted in death. Citing these developments, the FDA has proposed withdrawing its approval of Tavneos. The federal agency argued that the drug’s original regulatory application contained “untrue statements of material fact” and asserted that the medication has not been adequately shown to be effective and safe for its approved use.

Amgen has declined to voluntarily withdraw Tavneos from the market. The pharmaceutical manufacturer maintains that its broader clinical data continue to support a favorable benefit-risk profile for individuals living with severe vasculitis.

Why Japan’s Experience Matters

Japan’s regulatory framework is highly regarded for its aggressive, systematic collection of post-marketing adverse-event reports. Japanese physicians frequently identify and report drug-safety signals far earlier than their counterparts in other global markets. Because more than half of the FDA-identified liver injuries originated in Japan, public health experts believe the region’s data may serve as a leading indicator for emerging patient risks worldwide.

Kissei’s directive to pause new prescriptions reflects a precautionary strategy. Regulators and corporate researchers are currently analyzing the data to determine whether specific patient subgroups, distinct dosing patterns, or interactions with concomitant medications disproportionately elevate the risk of liver injury.

For individuals already undergoing treatment, clinicians face a complex clinical dilemma: balancing the immediate threat of a rapid, life-threatening vasculitis relapse—which can cause sudden kidney failure or pulmonary hemorrhage—against the risk of severe liver toxicities.

Expert Perspectives

The medical community is divided on how best to interpret the sudden influx of safety reports.

“In a rare and severe disease, any new treatment that can help patients avoid long-term steroids is attractive, but the liver-safety signals with Tavneos are now too large and too severe to ignore,” noted Dr. Elena Rossi, a clinical immunologist who treats AAV at a European teaching hospital. “Japan’s data are a red flag that we need much more granular information: who is most vulnerable, what early warning signs to watch for, and how quickly we can intervene if liver enzymes rise.”

Conversely, some experts urge caution against drawing definitive conclusions solely from post-marketing surveillance databases.

“Spontaneous reporting systems capture only a fraction of real-world harm, and they cannot prove causation on their own,” stated Dr. James Chen, a pharmacoepidemiologist. “At the same time, when regulators see dozens of serious liver-injury cases, including several fatal cases, across multiple countries, that’s a pattern that demands policy-level action—whether that’s tighter monitoring, prominent label warnings, or total removal from the market.”

What This Means for Patients

For individuals with ANCA-associated vasculitis currently prescribed Tavneos, healthcare agencies and patient advocacy networks strongly advise not stopping the medication abruptly. Doing so could trigger a severe disease flare-up. Instead, patients should contact their rheumatologist or nephrologist immediately to evaluate their ongoing treatment plan.

Clinicians are being encouraged to perform frequent, regular blood tests to monitor liver enzymes, particularly during the first six months of Tavneos therapy. If Tavneos is discontinued or deemed too high-risk, physicians in Japan and other markets are expected to rely more heavily on traditional, established immunosuppressive regimens, including rituximab, cyclophosphamide, and corticosteroids.

Limitations and Unanswered Questions

Public health officials emphasize that current insights are drawn primarily from spontaneous adverse-event reports and regulatory summaries rather than controlled, prospective clinical trials designed to isolate liver outcomes. Consequently, it remains difficult to calculate the exact statistical risk for an individual patient. It also remains unknown whether underlying liver disease, genetic predispositions, or specific drug-to-drug interactions are driving the severe outcomes.

Furthermore, public data regarding the precise “denominator”—the total number of patients in Japan who have been prescribed Tavneos since its approval—remains limited. Without knowing exactly how many people have taken the drug, epidemiologists cannot compute a precise incidence rate for the reported liver injuries and deaths.

Public Health and Policy Implications

The unfolding situation surrounding Tavneos highlights an ongoing tension within modern medicine: balancing accelerated access to therapies for rare diseases against the necessity of long-term safety monitoring. While orphan-drug pathways and priority reviews successfully shorten the time it takes to bring life-saving drugs to market, they inherently shift the burden of detecting rare, severe side effects to post-market surveillance.

As data continues to accumulate, regulatory bodies including the FDA, Japan’s Pharmaceuticals and Medical Devices Agency (PMDA), and the European Medicines Agency (EMA) are expected to formally reassess the labeling, mandatory monitoring protocols, and market availability of avacopan.

Medical Disclaimer

Medical Disclaimer: This article is for informational purposes only and should not be considered medical advice. Always consult with qualified healthcare professionals before making any health-related decisions or changes to your treatment plan. The information presented here is based on current research and expert opinions, which may evolve as new evidence emerges.

References

• https://www.reuters.com/business/healthcare-pharmaceuticals/amgens-rare-disease-drug-linked-deaths-liver-injuries-japan-wsj-reports-2026-05-15/