Amgen is pushing back against a request from US regulators to remove a drug for a rare autoimmune disease from the market, even as European regulators conduct a separate inquiry into data used to approve this medicine.

Both US and European regulators have raised concerns about the single study, ADVOCATE, which largely underpins the approval of avacopan (Tavneos) for certain forms of vasculitis under the umbrella term antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). In these conditions, the immune system’s attacks on blood vessels can cause severe damage to organs, including the lungs, heart, and kidneys.

Amgen has publicly announced that the FDA requested on January 16 that the company voluntarily withdraw avacopan from the US market. (Amgen gained the drug as part of its 2022 acquisition of ChemoCentryx.)

“The FDA raised concerns about the process followed by ChemoCentryx to re-adjudicate primary endpoint results for nine of the 331 patients in the ADVOCATE trial,” Amgen said. The company also said that the agency raised concerns about hepatotoxicity, an already known but infrequent risk of avacopan, “in the context of the benefit-risk profile of the medicine.”

Amgen said it informed the FDA on January 28 that it did not intend to withdraw avacopan from the market. The Thousand Oaks, California-based company said it is “confident” that avacopan “demonstrates effectiveness and a favorable benefit-risk profile.”

“Amgen is not aware of any issues with the underlying patient data and after review of the relevant clinical data and years of real-world evidence,” the company said.

Amgen has said it is “evaluating next steps with the FDA to determine a path forward, while keeping patient safety, needs, and support at the forefront.”

Separately, the European Medicines Agency last month announced that it’s conducting a review of the ADVOCATE trial. The agency said it will then issue a recommendation on whether the European Union marketing authorization for the drug should be maintained, amended, suspended, or revoked.

So far, Amgen and the FDA have provided little detail regarding the details of the agency’s request for the avacopan withdrawal, said Sharon Chung, MD, MAS, who directs the Vasculitis Clinic at the University of California, San Francisco. The FDA has not yet announced any plans for a public discussion on the request for a voluntary withdrawal of avacopan.

“I suspect the community would welcome an opportunity to share with the FDA their thoughts on the matter,” Chung told Medscape Medical News in an email exchange.

Avacopan may allow some patients with AAV to reduce steroid use. 

“Many of the toxicities patients experience with treatment are due to glucocorticoids, so avacopan [as shown in the studies] has the unique impact of sparing these toxicities for patients,” Chung said.

Chung said she didn’t believe there have been new risks found for avacopan.

“We have had patients experience increased liver enzymes when using this medication. The increases in liver enzymes, in our limited experience, have resolved with stopping the medication. Increases in liver enzymes are not uncommon when using other medications to treat autoimmune diseases (eg, methotrexate, azathioprine, JAK inhibitors, IL [interleukin]-6 targeting therapies), and so avacopan is not unique in this aspect,” she said.

Chung told Medscape Medical News that the new concern about hepatotoxicity arises from reports of vanishing bile duct syndrome (VBDS) occurring in patients in Japan. VBDS has not been reported in patients outside of Japan. Amgen is trying to obtain additional details regarding these cases to understand them further, she said.

She also said the FDA is expected to make its concerns with avacopan public via the Federal Register.

Adjudicating the Data

There have been persistent questions about how ChemoCentryx, the original developer of the drug, handled a key scoring issue in the ADVOCATE trial.

FDA officials noted this publicly in a 2021 review of avacopan.

At issue were differences in how the investigators in the ADVOCATE trial registered patients’ degree of illness on the Birmingham Vasculitis Activity Score (BVAS) compared with subsequent decisions made by an adjudication committee. The ADVOCATE trial was designed to measure remission, defined as a BVAS of 0 on a scale from 0 to 63. Higher BVAS scores indicate greater disease activity.

Chung told Medscape Medical News that there can be challenges in making assessments with the tool.

“My suspicion is that it has to do with the BVAS, which can be complicated to calculate,” Chung said. “Without knowing the details, I can’t comment on how this affects the strength of evidence for the medication.”

The FDA gave ChemoCentryx leeway in its avacopan application due to the need for more treatments for AAV. Prior to its approval, patients received off-label treatment with glucocorticoids and either cyclophosphamide or rituximab.

So ChemoCentryx was allowed to seek approval based on only one phase 3 trial instead of two.

But the FDA staff wrote that they then found “substantial uncertainties” about the ADVOCATE results.

For the study, a panel of vasculitis experts served on an adjudication committee. The aim of the committee was to ensure consistency in BVAS scoring across study centers in the ADVOCATE trial, the FDA staff noted in a briefing document.

The agency staff noted that the adjudication committee had tended toward lower BVAS scores, which could have impacted the study findings.

ChemoCentryx, in its briefing documents, said the adjudication committee assessed blinded BVAS data. The company also said the difference in the scores was “not surprising” because many investigators in the ADVOCATE trial were not as experienced in assessing BVAS as the committee members were.

On May 6, 2021, the FDA advisory committee narrowly endorsed the application. It voted 10-8 on the question of whether the risk-benefit profile of avacopan was adequate to support approval. Many of the members expressed reservations but cited the need for more treatments. The panel also voted 9-9 on a question about whether efficacy data support approval of avacopan for the treatment of adult patients with AAV.

The FDA approved avacopan in October 2021. Accompanying that approval were several FDA study mandates for the drug.

One was for a trial to evaluate safety outcomes, including hepatotoxicity and drug-induced liver injury, and serious hypersensitivity reactions, including angioedema and anaphylaxis. Another was for a trial to evaluate efficacy outcomes with long-term avacopan treatment.

The FDA approval of avacopan did not bring an end to questions about the ADVOCATE study data. These disputes were rehashed last year in public as part of a civil suit filed by investors who claimed ChemoCentryx overstated the safety and effectiveness of avacopan. They told the court they felt misled about the chances for the drug, due in part to how the adjudication process was handled.

In this case, US District Judge Jon S. Tigar in August 2025 found in favor of the defendant, Amgen.

“In sum, there is no triable issue of fact as to falsity because there is an absence of ‘any serious conflict between the FDA’s interim, albeit repeated, concerns about methodology and Defendants’ optimism about FDA approval,’ especially as the FDA ultimately approved avacopan based on the ADVOCATE trial,” Tigar wrote.

The FDA declined to comment during the week of February 16, 2026, on whether it will schedule a public hearing on avacopan.

Difficulty in Forcing Withdrawals From the Market

The agency has had difficulty in the past in taking drugs off the market when companies rebuffed its request for withdrawals.

Two of the more notable cases involved cases of accelerated approvals. With accelerated approval, the FDA clears a drug or a new indication for an approved one based on limited initial evidence, and then companies are expected to prove that their medicine works as expected through further study. (Avacopan’s clearance was not an accelerated approval.)

The FDA’s Center for Drug Evaluation and Research (CDER) in 2020 proposed the withdrawal of the Makena drug intended to prevent preterm birth after a major study failed to confirm its effectiveness. Covis, which sold the drug, requested a hearing on the matter, which was held in October 2022. That led the way to the withdrawal of the drug’s approval in 2023.

The FDA also had to build a case to remove a breast cancer indication from Genentech’s bevacizumab (Avastin) over the company’s objections. The CDER in 2010 found that an additional study did not confirm this indication for bevacizumab. Genentech then requested and was granted a hearing where the company could present its case to maintain the indication.

The FDA was not persuaded by the testimony from the June 2011 hearing on the bevacizumab indication. On November 18, 2011, the FDA issued a decision withdrawing approval of the breast cancer indication. 

FDA’s requests for voluntary withdrawals of medicines are relatively rare, and typically companies then proceed with the withdrawal, Mark Tobolowsky, JD, of the law firm Hyman, Phelps & McNamara, told Medscape Medical News in an email.

But in cases where companies don’t comply, the FDA then has to work through established steps to remove a drug from the market, he wrote.

“FDA has processes in place to withdraw an approval, including requirements to provide notice and an opportunity for a hearing on the proposal (unless there is an imminent hazard),” Tobolowsky wrote.

Makena was “a fairly extreme example” of the efforts the FDA must pursue for a withdrawal “because it went through the whole procedure, and then some,” Tobolowsky wrote. “But it’s not a quick process if the company is not cooperative.”

Chung reported having no relevant financial disclosures. Tobolowsky reported advising pharmaceutical and biotech companies on FDA matters.

Kerry Dooley Young is a freelance journalist based in Washington, DC. She has covered medical research and healthcare policy for more than 20 years.