EU revokes Tavneos approval citing serious clinical trial protocol breaches

European Union regulators have formally revoked the marketing authorisation for Tavneos, a treatment for rare autoimmune disorders, following a detailed assessment that identified significant irregularities in the pivotal clinical trial data. The European Commission adopted a recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) to withdraw the drug’s commercial clearance. This decision marks a definitive end to the medicine’s availability in Europe, where its marketing rights were held by CSL Vifor. The regulator’s move follows an extensive review of the evidence supporting the complement inhibitor, which had been approved in 2022 for treating active granulomatosis with polyangiitis and microscopic polyangiitis. The approval was originally granted on the basis that Tavneos could be used in combination with either rituximab or cyclophosphamide to manage these forms of ANCA-associated vasculitis.

The CHMP’s published documents outline serious breaches of good clinical practice principles regarding the handling of primary endpoint data in the phase three Advocate study. Regulators found that personnel involved in the trial were able to access unblinded efficacy data after an initial database lock. This access revealed that the drug had not demonstrated superiority at the critical 52-week mark. Armed with this knowledge, the CHMP alleges that study sponsors re-adjudicated the outcomes for nine patients. This process resulted in a rerun of the primary analysis, which shifted the result from non-significant to statistically significant for superiority. The regulator noted that the original analysis and these subsequent modifications were not disclosed to authorities. Instead, the clinical study report explicitly stated that the unblinding process outlined in the protocol had been followed, a claim the CHMP found inconsistent with the evidence of data manipulation.

In addition to concerns over data integrity, the European Medicines Agency highlighted serious safety issues associated with Tavneos. The regulator pointed to multiple reports of fatal cases involving drug-induced liver injury and vanishing bile duct syndrome among patients treated in the EU since the medicine’s initial authorisation. These safety signals had previously prompted several updates to the product information. The CHMP concluded that, given the unreliability of the pivotal study due to the serious breaches of clinical practice standards, there is no longer a demonstration that the benefits of Tavneos outweigh its risks, particularly concerning severe hepatic complications.

CSL Vifor, the operator responsible for Tavneos in Europe, confirmed it was disappointed by the European Commission’s final decision but stated it respected the outcome and was committed to implementing the withdrawal fully. Amgen, which acquired the drug’s original developer ChemoCentryx for $3.7 billion in 2022, has strongly contested the regulator’s findings. In a statement, the company expressed deep concern about the impact on patients with rare diseases and argued that the EMA failed to recognise the totality of evidence supporting Tavneos’ effectiveness. Amgen cited real-world studies and secondary endpoint data as justification for the drug’s value in helping patients achieve remission while reducing reliance on steroids.

The situation in the United States remains unresolved, with Amgen actively fighting to retain Tavneos on the market. The US Food and Drug Administration had requested a voluntary withdrawal earlier this year, citing similar safety and data concerns. Amgen initially resisted this request but has since submitted a comprehensive data package to the FDA to support a hearing. This submission includes a third-party re-evaluation of the Advocate study conducted by the Duke Clinical Research Institute, alongside real-world evidence and testimonials from patients and healthcare professionals. The FDA’s concerns regarding safety and potential data manipulation align closely with those raised by European regulators, setting the stage for continued regulatory scrutiny across both jurisdictions.