Amgen’s rare disease drug Tabneos is under increased regulatory scrutiny, with the FDA warning of severe liver damage, including deaths, among patients receiving the drug.
From the drug’s approval in 2021 through October 2024, 76 cases of drug-induced liver injury with “reasonable evidence” of a coincidental association with Tabneos were reported to the FDA Adverse Event Reporting System (FAERS), according to Tuesday’s safety communication.
This drug can be used as an adjunctive treatment for severe activated antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis. But the FDA is trying to change that by asking Amgen to withdraw the product, which the company has so far resisted.
The FDA said in a communication that nearly all cases of FAERS had severe outcomes, including 54 hospitalizations and eight deaths.
Based on 73 reports specifying the time from initiation of Tavneos treatment to the onset of liver damage, the agency estimated the median time to onset to be 46 days. The majority of cases (66) were reported in Japan, with five in the United States, four in Europe, and one in Canada.
Importantly, FAERS reporting alone cannot establish causation. However, FDA reviewed the available evidence to identify “reasonable evidence” of new safety concerns.
Seven of the reported cases involved vanishing bile duct syndrome (VBDS) as a complication of liver injury, which has also been found to be incidentally associated with Tabneos use, the FDA said. VBDS is a rare liver disease that causes progressive destruction and loss of bile ducts, signaled by jaundice, itching, and fatigue.
The FDA said VBDS and drug-induced liver injury (DILI) are two “emerging safety concerns” for Tabneos, adding to known hepatotoxic side effects.
Amgen has been aware of VBDS cases occurring in patients outside the United States since 2021 and has proactively submitted a proposed label update to add safety concerns in 2024, a company spokesperson told Fierce Pharma in an emailed statement. The request is “still pending” and Amgen continues to monitor the situation through post-market observational studies, the spokesperson added.
“Patient safety is always our top priority and we are in regular communication with the FDA regarding the safety of our medicines,” the spokesperson said, noting that the drug’s label already warns of severe liver toxicity (hepatotoxicity). “We remain confident that Tabneos is an important and effective medicine for severe ANCA-associated vasculitis, based on robust clinical data and real-world evidence demonstrating efficacy and a favorable benefit-risk profile.”
The FDA also continues to review post-marketing safety data and advises patients to be on the lookout for symptoms of potential liver damage.
The FDA said health care providers should regularly perform liver panel tests on patients taking the drug and stop treatment if potential symptoms are found.
Tabneos has come under increasing global regulatory pressure this year, with the FDA asking Amgen to voluntarily withdraw the drug from the market in January and the European Medicines Agency (EMA) beginning a review of the drug based on data integrity concerns. Amgen told the FDA in February of its intention to keep the drug on the market and said it was considering next steps to “determine a path forward.”
The FDA and EMA’s concerns stemmed from a pivotal trial behind Tavneos conducted by ChemoCentryx. Amgen acquired Chemocentrics for $3.7 billion in 2022, taking over Tabneos and, with it, the regulatory oversight that had surrounded the trial since a 2021 adversary committee meeting in which the FDA cited several efficacy and safety issues.
The FDA’s request for Amgen to discontinue the drug came as the company reviewed the risk-benefit profile and took a closer look at the results of the trial, particularly the primary endpoint, which was reevaluated for some patients.
“Amgen is not aware of any issues with the patient data underlying the Chemocentrics clinical trial,” the company said in its fourth quarter earnings call. “And after reviewing relevant clinical data and years of real-world evidence, Amgen is confident that Tabneos has demonstrated efficacy and a favorable benefit-risk profile.”
The company still has no intention of withdrawing Tabneos from the market, it reiterated in an emailed statement Tuesday.
