Amgen Inc. has secured extra time for its bid to keep selling avacopan (Tavneos) to treat a rare autoimmune disease, antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV). US regulators said the drug was approved in error in 2021 based on manipulated data from the pivotal study.

The FDA initially gave Thousand Oaks, California-based Amgen a deadline of June 29, 2026, to respond to the agency’s formal request for withdrawal of avacopan. Amgen told Medscape Medical News that the deadline has been extended to July 29, 2026.

At issue is how ChemoCentryx, a company acquired by Amgen in 2022 for about $3.8 billion, and employees of a contractor firm classified the treatment response of nine patients in the phase 3 ADVOCATE study.

The FDA said it relied heavily on this single study to establish substantial evidence of avacopan’s benefit and allow for its 2021 approval, with staff granting some additional flexibility in the review for the treatment for a rare disease.

The ADVOCATE study involved 331 patients with severe active AAV. They were randomly assigned to get either avacopan twice daily or a protocol-specified prednisone taper in a 1:1 ratio, the FDA said.

Even before avacopan’s approval, FDA staff raised questions about how patients’ responses to the drug were classified.

Litigation filed by ChemoCentryx shareholders brought more attention to these concerns. In its formal public request for avacopan’s withdrawal, the FDA said a revision, or re-adjudication, of reported results for nine patients allowed the company to claim a statistically superior outcome for the ADVOCATE study on the primary endpoint of sustained remission.

The FDA noted that a court last year dismissed the shareholders’ lawsuit, granting summary judgment in favor of ChemoCentryx, now owned by Amgen. That ruling does not have any bearing on the FDA’s responsibilities to ensure that drugs are safe and effective, the agency said.

“The court’s opinion did not acknowledge or address the data manipulation allegations” included in an expert report submitted by the plaintiff, the FDA also noted.

On June 29, The New England Journal of Medicine (NEJM) said it retracted its 2021 publication of a paper summarizing the ADVOCATE results at the requests of two authors employed by universities. In a note about the retraction, NEJM said that “without the knowledge of these two authors, the primary endpoint assessments in nine patients were readjudicated after database lock and trial unblinding.”

Liver Risk

The European Medicines Agency (EMA) in June recommended that avacopan be taken off the market, with the final decision on the drug’s authorization to be made by the European Commission. The EMA has advised that no new patients start the drug and that people already taking avacopan discuss other treatment options with their physicians.

In addition to rising doubt about avacopan’s effectiveness are concerns about its liver risk.

In March, the FDA issued a public alert about cases of liver injuries in people taking avacopan, including vanishing bile duct syndrome, or the destruction and disappearance of the bile ducts. The FDA then said patients should talk to their clinicians about avacopan’s risks and whether to continue therapy or switch to alternative treatments.

In a June 1 comment submitted to the FDA, Amgen said that there were “genuine and substantial issues of material fact” regarding the agency’s proposal for the avacopan withdrawal.

A hearing would allow the company to address these, as well as to make the case that avacopan’s benefits outweigh its risks for people with AAV, a rare and serious condition with few treatment options, Amgen said.

The Vasculitis Foundation, of which Amgen is a sponsor, asked the FDA to consider the view of patients in weighing whether avacopan sales continue. Many people taking the drug asked the FDA in their submitted comments to allow continued sales of avacopan, which they said has aided them.

Kerry Dooley Young is a freelance journalist based in Washington, DC. She has covered the FDA and drug safety issues for more than 20 years.