> ## Content Index > Fetch the complete content index at: https://nephspace.com/llms.txt > Use this file to discover other available public pages before exploring further. # Europe revoked avacopan after regulators called its pivotal trial's data unreliable. What now for patients doing well on it? - URL: https://nephspace.com/avacopan-revoked-europe-advocate-retraction/ - Published: 2026-11-02T11:57:00.000Z - Updated: 2026-11-02T11:56:59.000Z - Description: Europe revoked avacopan on August 4, after regulators called the ADVOCATE trial's efficacy data unreliable and weighed its liver-injury signal against it. The FDA alleges the one-year result was re-scored after unblinding; Amgen disputes it. A taskforce argues to keep access for a few. - Author: Dr Wael Hussein - Tags: Glomerular disease, #story, #has-audio, #opinion, #full-story, #news, Stories **🎧 Listen:** [Weekly · Nov 2](https://nephspace.com/weekly-nov-2/), from 08:19. ### What happened On August 4, 2026, the European Commission revoked the marketing authorization for avacopan, the oral C5a receptor antagonist used in ANCA-associated vasculitis to spare patients glucocorticoids. Europe's medicines committee had concluded that data-integrity problems in ADVOCATE, the pivotal phase 3 trial, made the efficacy dataset unreliable, and that post-marketing analyses could not replace it; the drug's liver-injury signal weighed heavily on the other side of the benefit-risk assessment. The committee recommended revocation on June 26, 2026, and the New England Journal of Medicine retracted the trial three days later, on June 29. ### What the FDA alleges about the trial Avacopan was approved on the strength of ADVOCATE, which randomized 331 patients to avacopan or a prednisone taper on top of standard induction, and reported non-inferiority for remission at week 26 and superiority for sustained remission at week 52, with substantially less glucocorticoid exposure. In a letter dated April 27, 2026, proposing to withdraw US approval, the FDA sets out a different sequence. After the first database lock, on November 5, 2019, and the unblinding that followed, the week-52 analysis was not statistically significant (p = 0.1025). Unblinded personnel at the sponsor, ChemoCentryx, then selected nine patients for re-adjudication, three in the control arm and six on avacopan, a step the adjudication committee's charter prohibited after database lock; the re-adjudications themselves were done blinded. Five patients in the avacopan arm were reclassified from not in sustained remission to sustained remission, and the application reported p = 0.0132\. The FDA says only the second analysis was ever disclosed to it, and concluded that it could no longer find substantial evidence of effectiveness and that the application contained "untrue statements of material fact." The two academic authors requested the retraction. Their notice says that, according to an ongoing FDA investigation conducted after publication and without their knowledge, the primary endpoint assessments in nine patients were re-adjudicated after database lock and trial unblinding, that this was not disclosed in the article, and that it is inconsistent with proper research conduct. An editorial in Arthritis & Rheumatology by Dr. Neeraj Dhaun's group in Edinburgh notes that the problem surfaced not through pharmacovigilance or inspection but through securities litigation, less than four years after approval. ### The company's response Amgen, which acquired ChemoCentryx in 2022, disputes the FDA's account, saying the re-adjudication followed a prespecified procedure and that no underlying clinical data were altered. It commissioned an independent, fully blinded re-adjudication of the ADVOCATE endpoints through the Duke Clinical Research Institute, which, according to the company, found avacopan non-inferior but not superior to the prednisone taper at week 26 and week 52, with a 56% reduction in glucocorticoid exposure. A hearing has been requested and the matter is unresolved. ### Liver safety, which weighed in the decision Hepatotoxicity was not a side issue in the European decision: the taskforce writes that it weighed heavily against the medicine in the overall benefit-risk assessment. The FDA has reported at least 76 cases of drug-induced liver injury with a reasonable causal association, including seven biopsy-confirmed cases of vanishing bile duct syndrome and eight deaths. Sixty-six of the 76 arose in Japan, as did six of the seven vanishing-bile-duct cases. The injury appears early and cholestatic: median onset was 46 days, and European monitoring requirements concentrate liver testing in the first six months. A systematic review of real-world data, from predominantly European practice, found no signal of acute liver failure. The Arthritis & Rheumatology editorial adds two further figures: in a US registry, any liver-test elevation occurred in about 5% of those tested, comparable to methotrexate, although liver tests were available for only 155 of 238 patients and monitoring fell short of the FDA label, so transient derangements may have been missed; Japanese cohorts report rates as high as 38%. ### Where each regulator stands As of September 18, 2026, per the taskforce: the EU authorization is revoked, with named-patient supply left to member states; the UK suspended new starts from September 1 and intends to revoke on March 1, 2027, with a six-month managed withdrawal for existing patients; Switzerland has announced withdrawal effective November 30, 2026, with no new starts and existing patients supplied until then; the US, Canada and Australia still authorize it, the US with a hearing requested and new starts allowed, Canada with a data-integrity review ongoing and new starts discouraged pending it, and Australia with a benefit-risk review ongoing; Japan briefly paused new starts in May 2026 and resumed under a revised label with intensified liver monitoring. ### What the taskforce argues Writing for the ERN RITA Autoimmune Vasculitis Taskforce, Professor Onno Teng and colleagues accept the population-level decision and do not contest it, and agree that stopping is defensible for most patients. Their argument is about an identifiable minority: a patient a year or more into treatment, in glucocorticoid-free remission with normal liver tests, for whom the period of highest hepatic risk has passed. Some patients flared after previously stopping and regained control on re-exposure. That cannot establish efficacy, they write, but it is informative for that patient's decision, and withdrawal is itself an intervention that may carry clinically important risk. Whether discontinuation causes harm is not established, but they call the possibility real and foreseeable, and note that a low late hepatic risk cannot be assumed with confidence. They ask for three things: named-patient supply on the treating physician's unsolicited order, a route EU law leaves to individual member states; criteria for continuation and for managed discontinuation shared across countries; and a compassionate-use program from the marketing authorization holder, so that remaining stock is redistributed rather than discarded. Their summary: this is "not a therapy that has failed, but a therapy whose pivotal phase 3 evidence failed … while previous phase 2 trials and accumulating real-world data continue to signal benefit." ### Why it matters here The editorial in Arthritis & Rheumatology draws the distinction that matters most in clinic: "Whether the ADVOCATE data were mishandled is a matter of research conduct; whether avacopan works and is safe is a matter of pharmacology and clinical evidence. The retraction does not, by itself, render the drug ineffective, but it means the evidence on which approval rested can no longer be relied upon, and that alone is reason to demand its benefit be reestablished on sound footing before continued wide use." The Lancet Rheumatology, in its own editorial, was blunter, writing that patients "seem set to lose access to an effective drug because of the nefarious actions of a few unscrupulous individuals." Our take for US clinicians: avacopan is still available here, and new patients can still be started on it, but the FDA has proposed withdrawal and a hearing is pending. If your patient is on avacopan, have the conversation now rather than when supply is forced: what we know, what we do not, and what the plan would be if the drug became unavailable. --- **The source:** Teng YKO, et al., for the ERN RITA Autoimmune Vasculitis Taskforce. Avacopan across borders: regulatory divergence and treatment dilemmas for ANCA-associated vasculitis. Nephrol Dial Transplant. Published online October 26, 2026\. doi:10.1093/ndt/gfag253 [Read the original](https://doi.org/10.1093/ndt/gfag253?ref=nephspace.com) **Also discussed:** - Rubin EJ. Retraction: Jayne DRW et al. Avacopan for the Treatment of ANCA-Associated Vasculitis. N Engl J Med. Published online June 29, 2026\. doi:10.1056/NEJMe2608684 [Link](https://doi.org/10.1056/NEJMe2608684?ref=nephspace.com) - US Food and Drug Administration, CDER. Tavneos (avacopan): proposal to withdraw approval; notice of opportunity for a hearing. April 27, 2026 [Link](https://www.fda.gov/media/192160/download?ref=nephspace.com) - Chapman GB, Pugh D, Dhaun N. From ADVOCATE to ADVOGATE: Is This the End of Avacopan? Arthritis Rheumatol. 2026\. doi:10.1002/art.70352 [Link](https://doi.org/10.1002/art.70352?ref=nephspace.com) - The Lancet Rheumatology. The end for avacopan. Lancet Rheumatol. 2026;8(8):e587 [Link](https://doi.org/10.1016/S2665-9913%2826%2900225-0?ref=nephspace.com) **🎧 Listen:** [Weekly · Nov 2](https://nephspace.com/weekly-nov-2/), from 08:19. *Physician-led, AI-assisted. Dr. Wael Hussein chooses every item NephSpace covers and reviews and edits every story before it is published. The first draft was written in our own words with AI (Claude, by Anthropic) from the full text of the editorial, the FDA's April 2026 letter, the NEJM retraction notice and two further editorials and checked against our reading notes; Dr. Hussein then reviewed and edited it. For education and information only, not medical advice. Please talk to your own physician or care team about your health. Clinicians: read the original before changing practice. See our* [*disclaimer*](https://nephspace.com/disclaimer/) *and* [*disclosures*](https://nephspace.com/disclosures/)*. Spotted an error?* [*Tell us*](mailto:hello@nephspace.com?subject=Correction)*.*