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Interim results from the AvacoStar safety study found liver abnormalities were more frequent among patients taking avacopan than among those receiving rituximab or cyclophosphamide. The events were uncommon, most had resolved by the data cutoff, and rates of serious infections, cardiac events and malignancies were not higher with avacopan. The study is ongoing, and the findings do not resolve questions about the drug’s U.S. market status or its earlier trial-data controversy.
Interim results from the AvacoStar safety trial found that patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) taking avacopan had a higher rate of liver abnormalities than patients receiving rituximab or cyclophosphamide, but the events were uncommon and generally resolved. Reported November 9 at the American College of Rheumatology’s annual meeting, the findings add safety data for a drug whose U.S. availability is under pressure after concerns about earlier trial results and reports of liver injury.
The study enrolled 504 people with highly active AAV in Britain and Germany: 254 received avacopan and 250 received rituximab or cyclophosphamide, selected at clinicians’ discretion. The interim analysis presented by Bernhard Hellmich, MD, of the University of Tübingen, used data through September 2025. More than 95% of participants were still receiving their initial treatment at that cutoff. Average treatment duration was 16.2 months for avacopan and 12.7 months for the alternatives.
Liver injury was the only one of four monitored categories of medical events that occurred at a significantly higher rate with avacopan. The reported incidence rate ratio was 4.03 (95% confidence interval 1.55-10.48); the absolute rate was 0.07 events per patient-year. The analysis recorded 22 liver events overall. Treating clinicians judged 10 probably or definitely unrelated to avacopan; among the 12 considered possibly, probably or certainly related, three patients continued regular dosing and five temporarily stopped treatment.
Twenty of the 22 liver events had resolved by the interim cutoff, Hellmich said. One other was later reported as resolved, while the remaining case had not resolved at the time of the presentation and was described by him as clinically irrelevant. Serious infections were reported at 0.14 per patient-year with avacopan and 0.18 with the alternatives. Cardiac events occurred at 0.09 per patient-year in both groups, while malignancies were reported at 0.02 per patient-year in each group.
What the Safety Findings Add
The results address a central concern about avacopan: liver injury is a known safety issue, and regulators have cited liver reports in scrutiny of the drug. In this interim study, the liver-event rate was higher with avacopan, but the absolute rate was low and most recorded events had resolved by the data cutoff. The other monitored event categories did not occur more often in the avacopan group in this analysis.
That evidence may inform discussions about whether avacopan should remain available in the United States, but it does not settle the question. The study was designed to assess safety, not to resolve the dispute about the drug’s original pivotal trial or independently establish its treatment benefit. Its findings also cover an interim period, not the full planned follow-up. For patients and clinicians weighing treatment options, the data offer additional comparative safety information while leaving longer-term risks under study.
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How Avacopan Reached This Review
Avacopan, marketed as Tavneos, was approved in the United States for AAV in 2021. It targets the complement pathway and was introduced as another treatment option alongside therapies including corticosteroids, rituximab and cyclophosphamide. The latter treatments also carry safety risks, while long-term corticosteroid use can cause serious adverse effects, according to the source report.
The drug’s position changed after questions emerged about its pivotal registration trial. The report says the original developer, ChemoCentryx, re-evaluated some trial outcomes after the study had been unblinded, shifting some participants from nonresponders to responders. The original results had missed the primary endpoint; after the changes, it was met. The FDA asked Amgen, which acquired ChemoCentryx in 2022, to withdraw avacopan voluntarily. Amgen had not agreed to that request, and the FDA had not made withdrawal mandatory, according to the report.
In March 2026, the FDA linked avacopan to eight deaths and 76 worldwide reports of drug-induced liver injury, including 54 hospitalizations. European regulators also acted: the European Union revoked the drug’s marketing authorization in August, and withdrawal in the United Kingdom is scheduled to be completed by March 2027. AvacoStar began in 2023 as a dedicated safety study and is funded by the joint venture that licensed avacopan in Europe.
“Residual bias”
— Bernhard Hellmich, MD, University of Tübingen, as reported by MedPage Today
Limits of the Interim Evidence
The reported results are interim, not final. AvacoStar is scheduled for completion in 2030, and additional years of follow-up could reveal risks not evident in the data presented. The source report also notes that treatment was chosen by clinicians, leaving room for differences between the patient groups that could affect comparisons.
The findings do not establish whether avacopan caused every liver event, and the analysis included clinician assessments of whether individual cases were related to the drug. Nor do the results determine whether the FDA will require a U.S. withdrawal, whether Amgen will change its position, or how regulators will weigh these findings against the earlier trial-data concerns and worldwide liver-injury reports. The study’s safety findings also do not answer questions about efficacy.
Further Follow-Up and U.S. Status
AvacoStar is expected to continue collecting medical-record data, with final study completion scheduled for 2030. Longer follow-up will show whether the interim pattern persists and whether additional safety events emerge. The source report does not provide a date for a next results release.
Separately, avacopan’s U.S. market status remains unresolved in the reported account: the FDA’s request was voluntary, and Amgen had not accepted it. Further decisions may depend on regulatory review of the accumulating safety evidence and the concerns surrounding the pivotal trial. No specific FDA decision or company action was reported alongside the interim results.
Key Questions
What did the AvacoStar interim analysis find?
It found that liver abnormalities occurred at a higher rate among patients taking avacopan than among those receiving rituximab or cyclophosphamide. The absolute avacopan rate was 0.07 events per patient-year. Rates of serious infections, cardiac events and malignancies were not higher in the avacopan group in this analysis.
Were the liver events severe or ongoing?
The report describes the events as uncommon and says 20 of 22 had resolved by the September 2025 interim data cutoff. One other was reported as resolved later. The final case had not resolved at that point and was described by Hellmich as clinically irrelevant; the report does not provide further clinical details.
Does this study settle whether avacopan will remain available in the United States?
No. The findings add safety information, but the U.S. market decision remains unresolved in the reported account. The FDA had asked Amgen to withdraw the drug voluntarily, and Amgen had not accepted that request; the agency had not made withdrawal mandatory.
When will the study be complete?
AvacoStar is ongoing, with final completion scheduled for 2030. The report did not identify a date for the next interim update.
Source: medpagetoday.com
