Because of these reports, Kissei issued a safety notice advising doctors to stop prescribing Tavneos to new patients and review treatment for existing patients due to the risk of severe liver damage.

Some of the deaths were associated with serious liver conditions that destroy bile ducts, though investigators have not confirmed that the drug caused every fatal case.

The warning intensified scrutiny of the drug’s safety profile worldwide, particularly because Tavneos is intended for patients with rare but serious autoimmune diseases such as granulomatosis with polyangiitis and microscopic polyangiitis.

FDA safety warnings and a proposal to withdraw approval

At the same time, U.S. regulators have raised their own concerns.

The U.S. Food and Drug Administration (FDA) has warned that post‑marketing reports link Tavneos to serious drug‑induced liver injury, including fatal cases and instances of vanishing bile duct syndrome, a severe condition in which bile ducts in the liver progressively disappear.

In April 2026, the FDA’s Center for Drug Evaluation and Research took an even stronger step by proposing to withdraw Tavneos from the U.S. market. The agency said new information indicates the drug has not been shown to be effective for its approved use, and it also alleged that the original approval application contained “untrue statements of material fact.”

That proposal initiates a regulatory process; it does not necessarily mean the drug has already been removed from the market.

Evidence that liver injury may be more common in Japan

Several studies have suggested that liver injury associated with avacopan appears more frequent in Japanese patients than in Western populations.

Real‑world analyses have reported:

• 16.7%–40.9% liver‑injury rates in Japanese cohorts
• Compared with 0% in Spain, 4.3% in the United States, and 5.1% in Germany in some reports

Another pharmacovigilance study found that Japanese patients had a significantly higher risk of liver dysfunction than American patients (p < 0.001) when taking avacopan.

Researchers emphasize that these findings show a safety signal but do not prove the drug caused every liver injury or death.

Possible reasons for the higher risk

Scientists have not yet identified a definitive explanation for the apparent geographic differences in liver toxicity.

Potential contributing factors under investigation include:

• Population differences, including genetics or age distribution
• Differences in clinical practice or monitoring
• Concomitant medications that affect drug metabolism
• Underlying disease characteristics in treated patients

Avacopan is metabolized through the CYP3A4 enzyme pathway, meaning that drugs that inhibit or induce this pathway can significantly change drug exposure levels. This could influence toxicity risk, though it does not fully explain the higher rates observed in Japan.

What remains uncertain

Despite mounting scrutiny, several key issues remain unresolved:

• A direct causal link has not been confirmed for every reported death in Japan.
• The FDA’s proposed withdrawal still requires completion of regulatory procedures.
• Researchers have not yet identified a clear biological mechanism explaining why Japanese patients appear more vulnerable to liver injury.

For now, Tavneos remains an example of how post‑marketing safety data can dramatically reshape a drug’s risk‑benefit profile after approval—especially for treatments targeting rare diseases where early clinical trials may involve relatively small patient populations.

Because of these reports, Kissei issued a safety notice advising doctors to stop prescribing Tavneos to new patients and review treatment for existing patients due to the risk of severe liver damage.

Some of the deaths were associated with serious liver conditions that destroy bile ducts, though investigators have not confirmed that the drug caused every fatal case.

The warning intensified scrutiny of the drug’s safety profile worldwide, particularly because Tavneos is intended for patients with rare but serious autoimmune diseases such as granulomatosis with polyangiitis and microscopic polyangiitis.

FDA safety warnings and a proposal to withdraw approval

At the same time, U.S. regulators have raised their own concerns.

The U.S. Food and Drug Administration (FDA) has warned that post‑marketing reports link Tavneos to serious drug‑induced liver injury, including fatal cases and instances of vanishing bile duct syndrome, a severe condition in which bile ducts in the liver progressively disappear.

In April 2026, the FDA’s Center for Drug Evaluation and Research took an even stronger step by proposing to withdraw Tavneos from the U.S. market. The agency said new information indicates the drug has not been shown to be effective for its approved use, and it also alleged that the original approval application contained “untrue statements of material fact.”

That proposal initiates a regulatory process; it does not necessarily mean the drug has already been removed from the market.

Evidence that liver injury may be more common in Japan

Several studies have suggested that liver injury associated with avacopan appears more frequent in Japanese patients than in Western populations.

Real‑world analyses have reported:

• 16.7%–40.9% liver‑injury rates in Japanese cohorts
• Compared with 0% in Spain, 4.3% in the United States, and 5.1% in Germany in some reports

Another pharmacovigilance study found that Japanese patients had a significantly higher risk of liver dysfunction than American patients (p < 0.001) when taking avacopan.

Researchers emphasize that these findings show a safety signal but do not prove the drug caused every liver injury or death.

Possible reasons for the higher risk

Scientists have not yet identified a definitive explanation for the apparent geographic differences in liver toxicity.

Potential contributing factors under investigation include:

• Population differences, including genetics or age distribution
• Differences in clinical practice or monitoring
• Concomitant medications that affect drug metabolism
• Underlying disease characteristics in treated patients

Avacopan is metabolized through the CYP3A4 enzyme pathway, meaning that drugs that inhibit or induce this pathway can significantly change drug exposure levels. This could influence toxicity risk, though it does not fully explain the higher rates observed in Japan.

What remains uncertain

Despite mounting scrutiny, several key issues remain unresolved:

• A direct causal link has not been confirmed for every reported death in Japan.
• The FDA’s proposed withdrawal still requires completion of regulatory procedures.
• Researchers have not yet identified a clear biological mechanism explaining why Japanese patients appear more vulnerable to liver injury.

For now, Tavneos remains an example of how post‑marketing safety data can dramatically reshape a drug’s risk‑benefit profile after approval—especially for treatments targeting rare diseases where early clinical trials may involve relatively small patient populations.