Amgen’s rare disease drug Tavneos is under mounting regulatory scrutiny, with the FDA warning of serious liver injuries, including some fatalities, among patients who received the drug.
From the drug’s approval in 2021 through October 2024, 76 cases of drug-induced liver injury with “reasonable evidence” of a causal association to Tavneos were reported to the FDA Adverse Event Reporting System (FAERS), according to a Tuesday safety communication.
The medicine is available as an adjunct treatment for severe active anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis. But the FDA is looking to change that with a request for Amgen to withdraw the product, which the company has so far resisted.
Nearly all of the cases in FAERS resulted in a serious outcome, including hospitalization in 54 patients and death in 8, the FDA said in the communication.
Based on 73 reports that specified the time from Tavneos initiation to liver injury onset, the agency flagged a median time to onset of 46 days. The vast majority of the cases (66) were reported in Japan, with five in the U.S., four in Europe and one in Canada.
Importantly, reports in FAERS alone do not establish causality. But the FDA reviewed the available evidence to identify “reasonable evidence” of new safety concerns.
Vanishing bile duct syndrome (VBDS) occurred as a complication of liver injury in seven of the reported cases and has also been determined to have a causal association with Tavneos use, the FDA said. VBDS is a rare liver condition that causes the progressive destruction and loss of bile ducts and is signaled by jaundice, itchiness and tiredness.
VBDS and drug-induced liver injury (DILI) are two “new safety concerns” for Tavneos, the FDA said, and join the known adverse reaction of hepatotoxicity.
Amgen has been aware of VBDS cases in patients outside of the U.S. since 2021 and proactively submitted a proposed label update in 2024 to add the safety concern, a company spokesperson told Fierce Pharma in an emailed statement. The request is “still pending,” and Amgen continues to monitor the situation through its post-marketing and observational studies, the spokesperson added.
“Patient safety always comes first, and we are in regular communication with the FDA about the safety of our medicines,” the spokesperson said, noting that the drug's label already warns of serious liver toxicity (hepatotoxicity). “We remain confident that Tavneos is an important and effective medicine for severe ANCA-associated vasculitis based on robust clinical data and real-world evidence demonstrating the effectiveness and favorable benefit–risk profile.”
The FDA is also continuing to scour post-marketing safety data and advises patients to keep an eye on potential liver injury symptoms.
Providers should conduct regular liver panel testing for patients on the drug and discontinue treatment if potential symptoms are spotted, the FDA said.
Tavneos has been under increased global regulatory pressure this year, with the FDA in January asking Amgen to voluntarily withdraw the drug from the market and the European Medicines Agency (EMA) initiating a re-review of the med based on data integrity concerns. In February, Amgen said it had informed the FDA that it intended to keep the medicine on the market and that it was evaluating next steps to “determine a path forward.”
The FDA and the EMA’s concerns stemmed from the pivotal trial behind Tavneos, which was run by ChemoCentryx. Amgen picked up ChemoCentryx for $3.7 billion in 2022, inheriting Tavneos and with it the regulatory scrutiny that had surrounded the trial since a 2021 adversary committee meeting, during which the FDA flagged several efficacy and safety issues.
The FDA’s request for Amgen to pull its drug came as the agency reviewed its risk-benefit profile and took a closer look at the trial, specifically at its re-adjudicated primary endpoint results for some patients.
“Amgen is not aware of any issue with the underlying patient data from the ChemoCentryx clinical trial,” the company wrote in its fourth-quarter earnings release. "And after review of the relevant clinical data and years of real-world evidence, Amgen is confident that Tavneos demonstrates effectiveness and a favorable benefit-risk profile.”
The company still does not intend to withdraw Tavneos from the market, it reiterated in its emailed statement Tuesday.