After the drug’s local license holder called for a brief pause in new patient starts last week, doctors in Japan can once again prescribe Amgen’s rare autoimmune disease med Tavneos (avacopan), albeit with revised safety precautions tucked into the product packaging.
The temporary spot of turbulence for Tavneos—which is overseen in Japan by Matsumoto-based Kissei Pharmaceutical—comes as the ANCA-associated vasculitis (AAV) med faces scrutiny around its trial data and safety in other key markets, such as Europe and the United States.
Despite recent setbacks, Amgen continues to stand behind Tavneos, which it acquired in its $3.37 billion ChemoCentryx buyout back in 2022. Earlier this year, the company resisted a push by the FDA to withdraw the complement 5a receptor (C5aR) antagonist in the United States, where Amgen holds Tavneos marketing rights.
Kissei divulged (PDF) the new precautions to Tavneos’ Japan package insert in a filing on the Tokyo Stock Exchange Thursday, with an Amgen spokesperson also confirming the development to Fierce. The change in guidance follows discussions between Kissei and Japan’s Ministry of Health, Labour and Welfare, the company said.
“We understand Japan’s regulatory authority is working with Kissei to update the Tavneos prescribing information in Japan to include a warning on serious liver injury, specific liver monitoring recommendations and criteria for stopping treatment,” Amgen’s spokesperson said in an emailed statement.
“Importantly the Ministry of Health, Labour and Welfare (MHLW) stated that providers may prescribe Tavneos to new patients, updating their recommendation from May 15, 2026,” the spokesperson added.
Last Friday, Kissei put the call out to healthcare professionals in Japan to refrain from using Tavneos in new patients “for the time being” and to “carefully assess the necessity of continued administration for patients who were currently undergoing treatment” in the wake of 20 reported fatal cases of serious liver injury among Tavneos patients in the country, according to the Japanese company’s filing.
In its own release at the time, Amgen noted that those deaths came from a pool of more than 8,500 patients treated with Tavneos in Japan and included “cases for which a causal relationship with the product could not be determined.”
“Based on all available data, Amgen continues to believe Tavneos demonstrates effectiveness and a favorable benefit-risk profile for patients living with AAV,” the company said last week.
Kissei—which acquired Japan rights to Tavneos in 2017 through a deal with Vifor Fresenius Medical Care Renal Pharma—secured a domestic green light for the drug in September 2021 to treat granulomatosis with polyangitis (GPA) and microscopic polyangiitis (MPA), which are the two main types of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis.
AAV is a rare and severe autoimmune disease that causes damage to various organs, including the kidneys, lungs and nervous system. At the time of approval, Kissei estimated that more than 10,000 people in Japan were living with the condition.
The revisions to the Tavneos insert in Japan fall under the precautions for use section, which now includes a warning that serious liver dysfunction, including vanishing bile duct syndrome, can occur, and that cases of death have been reported. In turn, it’s advised that doctors conduct regular liver function tests on patients before and during administration, followed by close monitoring, according to Kissei’s filing.
The insert also notes that liver dysfunction, when it occurs, often happens within the first three months of the drug’s administration. The document further provides information on the timing of liver function tests and the sorts of observations that might necessitate an intervention on an HCP’s part.
Kissei added that it has established a "Drug Consultation Center" for healthcare professionals and patients to help field any questions on the situation, too.
“The U.S. prescribing information has included information on the risk of serious liver injury (hepatotoxicity), as well as liver monitoring and treatment discontinuation guidance for physicians and patients, since FDA approval in 2021,” Amgen’s spokesperson told Fierce of Tavneos’ U.S. label Thursday.
The spokesperson added: “These updates by MHLW will help ensure healthcare providers and patients in Japan have the most current information to support treatment decisions for ANCA-associated vasculitis, a rare and potentially life-threatening disease.”
Liver injury concerns have also informed scrutiny of Tavneos in the U.S., where the FDA requested that Amgen withdraw the drug in mid-January over questions on the integrity of the data behind the med’s pivotal trial run by ChemoCentryx, and amid a review of the medication’s risk-benefit profile.
But Amgen pushed back, writing in its fourth-quarter earnings release that it was “not aware of any issue with the underlying patient data from the ChemoCentryx clinical trial.” The company stood behind Tavneos and said it would evaluate next steps to “determine a path forward” with the FDA.
Days before Amgen publicly disclosed the situation in the U.S., regulators in the European Union announced that they too would re-review Tavneos over phase 3 data concerns.
Then, in late March, the FDA issued a safety communication flagging 76 cases of drug-induced liver injury with “reasonable evidence” of causal association to Tavneos reported to the agency’s Adverse Event Reporting System (FAERS) from the drug’s approval in 2021 through October 2024. The cases logged in the database—which do not alone establish causality—led to 54 hospitalizations and 8 deaths, the FDA said at the time.
At the time, an Amgen representative told Fierce that “[p]atient safety always comes first, and we are in regular communication with the FDA about the safety of our medicines,” adding that the company remained confident in the drug’s risk-benefit profile.
On Thursday, the company’s spokesperson stressed that “[t]here 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.”
Meanwhile, late last month, the FDA escalated its scrutiny of the drug, proposing to withdraw Tavneos’ U.S. approval over assertions that new information suggested pivotal data was “manipulated” to score a green light. Aside from drawing the drug’s effectiveness into question, the FDA’s Center for Drug Evaluation and Research also noted that it has become “increasingly concerned about the safety of Tavneos” in relation to cases of serious drug-induced liver injury.
The FDA gave Amgen the option to pull Tavneos from the market or request a hearing. Amgen noted that it disagreed with the FDA’s position and was weighing its next options, according to a statement to Fierce in late April.