Comment from Anonymous

I am writing in support of FDA’s proposal to withdraw approval of TAVNEOS (avacopan) capsules, 10 mg, under Docket No. FDA-2026-N-1321. I am a practicing rheumatologist who treats patients with ANCA-associated vasculitis. In my clinical experience, I have concerns that the real-world benefit of avacopan is questionable, while the potential risks, including hepatotoxicity, are clinically meaningful. For a serious disease such as ANCA-associated vasculitis, where patients may already be medically fragile and receiving other immunosuppressive therapies, the evidentiary standard for benefit should be clear and reliable. I can say that in the dozen or more patients that I have treated with avacopan, I have not seen any true improvement that I can trace to the use of avacopan. I have also seen evidence of hepatotoxicity in patients and have subsequently discontinued its use in my clinic despite the original positive data from ChemoCentryx. Amgen has refused to provide any further clinical data despite my attempts to pursuade them to provide such information. They appear to desire to get the benefits of the purchase of avacopan without investing further in helping rheumatologists understand the true risk/benefit of the drug. FDA’s notice states that the proposed withdrawal is based in part on a lack of substantial evidence of effectiveness and untrue statements of material fact in the application. FDA also describes concerns that the pivotal ADVOCATE study results were altered after database lock and unblinding, with readjudications that changed the primary efficacy analysis from non-significant to significant. Those concerns are highly troubling for a medication being used in a potentially life-threatening disease. I also believe the original trial is no longer adequately applicable to the current treatment environment for ANCA-associated vasculitis. Treatment standards have continued to evolve, and the role of avacopan should be reassessed in a modern, well-controlled clinical trial using contemporary background therapy, clinically meaningful endpoints, appropriate safety monitoring, and rigorous prespecified statistical methods. My recommendation is that TAVNEOS be withdrawn from the market at this time. If the sponsor believes avacopan has an appropriate role in ANCA-associated vasculitis, it should be required to conduct further studies before reintroduction, beginning with a properly designed Phase 3 trial that can clearly establish whether the medication is truly effective and whether its benefits outweigh its risks in current clinical practice. Thank you for considering this comment.