Japan Questions Tavneos Approval Data as Liver Deaths Put Drug Under Review

Japan weighs action over trial data and liver injuries

Japan's health ministry said on October 21, 2026, that documents submitted by Kissei Pharmaceutical Co. to secure approval for the vasculitis medicine Tavneos may have reliability problems, adding concerns about the drug's clinical trial evidence to an existing investigation into fatal liver injuries.

The ministry reiterated its request that medical institutions avoid starting new patients on Tavneos. It plans to decide by the end of 2026 whether to take administrative action, potentially including revoking the drug's approval.

Japan's Pharmaceuticals and Medical Devices Agency found that assessments of clinical trial cases had been redone using inappropriate methods. Such assessments help determine whether patients improved during a trial and whether a medicine met the conditions used to judge its effectiveness.

Tavneos, also known as avacopan, went on sale in Japan in June 2022. Its product information already lists liver dysfunction as a serious adverse reaction. Kissei reported in May that 20 people taking the medicine had died with liver dysfunction, although one death was later found to have another cause.

The Japanese review brings together two issues with immediate consequences for patients: the reliability of the evidence supporting approval and the risk of severe liver damage during treatment. Similar concerns have prompted regulatory scrutiny in the United States and Europe.

What Japan found in the approval evidence

The Japanese agency's finding concerns how trial cases were evaluated, including the use of inappropriate methods to reassess them. Clinical trial results depend on consistent rules for deciding whether a treatment has worked. Reassessing cases can change the results used by regulators to weigh a medicine's benefits against its risks.

The ministry has not announced its final administrative decision. Its stated deadline is the end of this year, while the request to avoid starting new patients remains in place.

Kissei has said it is providing necessary information to the Pharmaceuticals and Medical Devices Agency and continuing discussions with the health ministry. The company began urging health professionals on May 15 to refrain from prescribing Tavneos to new patients.

For people already taking the medicine, Kissei asked medical professionals to explain the liver risks and decide whether treatment should continue. That makes a review with the treating clinician the immediate practical step for existing patients.

How the Japanese safety figures developed

An estimated 8,503 patients in Japan had received Tavneos as of April 27. By the May announcement, Kissei had reported 22 cases of vanishing bile duct syndrome, a serious condition involving damage to the small channels that carry bile out of the liver.

Thirteen of the 20 deaths initially reported were associated with that condition. Twenty of the 22 cases of vanishing bile duct syndrome developed within three months of starting treatment, placing much of the reported harm early in the course of treatment.

Kissei added vanishing bile duct syndrome to the serious adverse reactions listed in the medicine's product information on May 1. The later finding that one of the 20 deaths had another cause changes the original fatality account; the company had also said that a causal relationship with Tavneos could not be determined in some cases.

In its May 15 statement, Amgen, which holds the drug's United States rights, described the Japanese reports as 20 fatal cases of serious liver injury among more than 8,500 treated patients. It said some included cases had an uncertain causal relationship with the medicine.

Amgen also addressed the United States experience in that statement:

There have been no known deaths in the U.S. linked to serious liver injury, including vanishing bile duct syndrome (VBDS), in the more than 8,000 patients in the U.S. treated with TAVNEOS.

The company's statement describes its position in May. The Japanese ministry's October announcement adds the subsequent death reclassification and its concerns about the approval documents.

What the FDA found in its liver injury review

The United States Food and Drug Administration set out detailed safety findings in its March 31 safety communication. Reviewing cases recorded through October 9, 2024, the agency identified 76 instances of drug induced liver injury with reasonable evidence of a causal association with avacopan.

Seventy-four cases involved a serious outcome, including 54 hospitalizations and eight deaths. Japan accounted for 66 of the 76 cases, about 87 percent, compared with five from the United States, four from Europe and one from Canada.

The FDA's eight deaths came from its review of cases through October 2024; Kissei's original figure of 20 concerned its later Japanese reporting. The two figures cover different reporting periods and case groups.

Among 73 cases with information on timing, the median interval between starting avacopan and developing liver injury was 46 days. The shortest interval was 22 days and the longest was 140 days. A median of 46 days means half of those cases began sooner and half later.

The FDA drew its findings from the applicant's global safety database, published medical literature and the agency's adverse event reporting database. It said fatal liver injuries and vanishing bile duct syndrome represented new safety concerns, even though liver toxicity had already been identified during clinical trials and included in product labeling.

Why damage to bile ducts can become serious

Vanishing bile duct syndrome occurs when bile ducts inside the liver are progressively destroyed and disappear. Bile is a fluid that helps the body digest fats and carry away certain waste products. When its passage is blocked or reduced, substances that should leave the liver can build up.

The FDA identified seven cases of this syndrome confirmed by biopsy, a procedure in which a small tissue sample is examined. All seven patients were hospitalized and three died. Six cases were reported from Japan and one from Canada.

Those seven cases were included within the FDA's 76 liver injury cases. The median time to liver injury in this smaller group was also 46 days, with cases beginning between 33 and 59 days after treatment started.

The agency warned that the condition can cause permanent liver damage. Yellowing of the skin or eyes, itching and tiredness can accompany it. These symptoms matter because liver damage may first become noticeable through changes that a patient might otherwise attribute to illness or everyday fatigue.

What patients and clinicians are being told

The FDA recommends liver panel testing every two weeks during the first month of Tavneos treatment, monthly for the next five months and afterward when clinically indicated. These blood tests measure substances that can signal liver cell damage or problems with bile flow.

Its instructions call for clinicians to promptly discontinue Tavneos, evaluate the patient and consider alternative treatment if the liver enzymes ALT or AST exceed three times the upper limit of normal, or alkaline phosphatase exceeds twice that limit. The agency gives the same instruction when patients show symptoms of impaired bile flow, such as jaundice or itching.

Patients whose abnormal tests or symptoms do not improve should be referred to a hepatologist, a doctor specializing in liver disease, according to the FDA.

The agency advises patients to contact their health professional immediately for unusual tiredness, nausea, vomiting, unusual itching, pale stools, yellow skin or eyes, dark urine, abdominal swelling or pain in the upper right abdomen. It also asks patients to discuss whether to continue Tavneos or switch to another treatment with their clinician.

Japan's request concerns avoiding new prescriptions, while decisions for existing patients require an assessment of their treatment and liver risks. The underlying disease can itself damage major organs, making continued medical care essential during any change in medication.

Why Tavneos is used for a serious disease

Tavneos treats severe active anti-neutrophil cytoplasmic autoantibody associated vasculitis, usually shortened to ANCA associated vasculitis. This is a group of rare diseases in which the immune system attacks blood vessels, causing inflammation that can harm organs.

The FDA approved Tavneos on October 7, 2021, for adults with granulomatosis with polyangiitis or microscopic polyangiitis, two forms of the disease. In the United States, it is used alongside glucocorticoids and other standard treatments. Glucocorticoids are medicines that reduce inflammation and suppress immune activity.

The FDA states that Tavneos does not eliminate the use of glucocorticoids. Patients may therefore be receiving several medicines as part of a treatment plan, rather than taking Tavneos alone.

Amgen defended the medicine's effectiveness and its balance of benefits and risks in its May statement. The company said serious liver injury warnings and guidance on liver monitoring had appeared in United States prescribing information since approval in 2021. Regulators are now examining both the safety experience after launch and the evidence used to support approval.

How the regulatory scrutiny unfolded

Japan's October announcement follows months of action involving the medicine's trial evidence and liver risks. The main developments span several jurisdictions:

• January 30, 2026: The European Medicines Agency began a review following concerns about the integrity of data from a late stage clinical trial.
• March 31: The FDA issued its safety communication on serious liver injuries, including fatal cases and vanishing bile duct syndrome.
• April 27: The FDA's Center for Drug Evaluation and Research proposed withdrawing United States approval, citing a lack of demonstrated efficacy and materially inaccurate statements in the approval application.
• May 1: Kissei added vanishing bile duct syndrome to the Japanese product information.
• May 15: Kissei began urging clinicians to avoid starting new patients on Tavneos.
• October 21: Japan's health ministry announced reliability concerns about the approval documents and reiterated its request on new patients.

The United States withdrawal proposal and Japan's possible revocation are regulatory steps under consideration. Japan's ministry has set the end of 2026 as its deadline for deciding its administrative response.

Which companies are responsible for the medicine?

Kissei, based in Matsumoto in Nagano Prefecture, obtained exclusive Japanese rights to Tavneos in 2017 from Vifor Fresenius Medical Care Renal Pharma. Vifor had acquired commercial rights for selected markets from the developer, ChemoCentryx, in 2016.

Amgen acquired ChemoCentryx in 2022 and holds the United States rights. In its May statement, Amgen said interactions with regulators, clinicians and patients outside the United States are handled by the companies holding rights in those jurisdictions.

Tavneos is a substantial product for Kissei. The company recorded 11.52 billion yen in sales from the medicine in fiscal 2025, against total sales of 97.41 billion yen. Those figures put Tavneos at about 11.8 percent of its sales, or close to one yen in every eight.

Kissei said in May that it was assessing the effect on its business performance. For patients and medical institutions, the immediate focus is the ministry's request to avoid new treatment starts, careful review of existing treatment and the regulatory decision expected before year end.

Key Points

• Japan identified reliability concerns in Tavneos approval documents, including inappropriate reassessment of clinical trial cases.
• The health ministry reiterated its request to avoid starting new patients and plans a decision by the end of 2026, potentially including revocation of approval.
• Kissei initially reported 20 deaths involving liver dysfunction; one death was later attributed to another cause.
• The FDA identified 76 liver injury cases through October 2024, including eight deaths. Sixty-six cases came from Japan.
• Serious bile duct damage and liver injuries often appeared early in treatment, supporting close monitoring and prompt clinical review of symptoms.
• European trial data scrutiny and a United States proposal to withdraw approval add to the medicine's regulatory uncertainty.