On April 29, 2026, the FDA published a notice in the Federal Register (FR) (posted on the FR prepublication page (here)) announcing the FDA’s intention to withdraw approval of the New Drug Application (NDA) for TAVNEOS (avacopan) capsule, 10 milligrams (mg), held by ChemoCentryx, Inc. and offer the applicant an Opportunity for a Hearing regarding the FDA’s proposed action.
The notice provides a detailed description of the facts for which the FDA has concluded that, “[g]iven the material omissions and untrue statements in the application, the applicant has falsely certified that the data and information in its application submissions for NDA 214487 were ‘true and accurate.’ The applicant’s omissions and untrue statements were material to the review of NDA 214487, including the determination of substantial evidence of effectiveness, the overall benefit-risk assessment, the recommendation of the Director of the Division of Rheumatology & Transplant Medicine to approve the NDA, and the decision of the Director of the Office of Immunology & Inflammation to approve the NDA.”
According to the FDA, the firm inappropriately manipulated study data after the first data lock. In general, according to the FDA, the firm did so by “selectively” reassessing some patient data after unblinding and changing the study participants’ responses to the drug, which changed the initial statistical analysis. The FDA concluded that the study failed to meet its primary endpoint to yield a positive statistical result that demonstrated a significant difference from the control arm. The FDA notes that the NDA (as submitted) failed to mention these facts and purported that there was only one data lock when there was a previous data lock prior to changes in the statistical evaluation.
The Agency states, in the FR notice, that “[i]n light of the facts outlined above [in the FR notice], CDER can no longer conclude that there is, or has ever been, a valid demonstration of substantial evidence of effectiveness for TAVNEOS. The post hoc nature of the database changes and involvement of unblinded study personnel, combined with the resulting change in statistical significance, irrevocably compromises the credibility of the study results and thus the demonstration of substantial evidence of effectiveness that supported the original approval.”
“Accordingly, CDER proposes to withdraw approval of TAVNEOS (avacopan) capsule, 10 mg, because, on the basis of new information, evaluated together with the evidence available to FDA when the NDA was approved, there is a lack of substantial evidence of effectiveness that the drug will have the effect it is purported or represented to have under the conditions of use prescribed, recommended, or suggested in its labeling. This absence of demonstrated benefit is further aggravated by the drug’s known serious risks of hepatoxicity. In addition, CDER proposes to withdraw approval of the drug because the application contained untrue statements of material fact, as described in Section I.E” of the FR notice.
In addition, the FDA notes that “hepatotoxicity was identified as a key safety risk in the original NDA review. In addition, serious and sometimes fatal cases of hepatotoxicity have been reported postmarketing, and recent post-market safety reports suggest that avacopan may also be associated with vanishing bile duct syndrome (VBDS), a serious and, at the time of approval, unexpected adverse event. In light of our finding that there is a lack of substantial evidence of efficacy, there is no demonstrated benefit to balance the risks associated with TAVNEOS.”
The FR notice is fascinating reading and, depending on the firm’s response and the FDA’s action, this case presents a lesson learned to all relative to dealing with study data and its interpretation.
