Amgen New Data Pushes Back Against Proposal to Withdraw Tavneos
Amgen has submitted to FDA new scientific data and analyses in its bid to prevent the withdrawal of Tavneos (avacopan), arguing that the treatment continues to demonstrate a favorable benefit-risk profile for patients with severe active ANCA-associated vasculitis (AAV), a rare and potentially life-threatening autoimmune disease. The company said it filed the materials on 7/23 as part of its formal request for an FDA hearing, contending that the available evidence satisfies the statutory standard for substantial evidence of effectiveness.
The dispute follows FDA's April proposal to remove the drug from the U.S. market (see story), concluding the therapy lacks reliable evidence of effectiveness and raising serious concerns about data integrity in the application submitted by its subsidiary ChemoCentryx. FDA said in its proposal that its original approval decision relied on what it now considers inaccurate and misleading representations of clinical trial data from the pivotal ADVOCATE study. It says the trial failed to demonstrate statistical significance on its prespecified primary endpoint — sustained remission at 52 weeks — in the original analysis, a fact it says was not understood by key officials at the time of approval. FDA alleges that subsequent, undisclosed analyses and data handling produced a nominally significant result that formed the basis of the approval decision.
“Absent manipulation, the study results were not statistically significant,” FDA wrote, adding that the integrity of the trial was compromised by deviations from established protocols designed to minimize bias. The agency emphasizes that these undisclosed actions were material to its approval decision.
Amgen said its submission includes new analyses, post-marketing data, and real-world evidence intended to address the agency's concerns while emphasizing the importance of preserving treatment options for patients with limited alternatives. The company also argued that Tavneos helps reduce reliance on prolonged corticosteroid use, which is associated with serious long-term complications including infections, osteoporosis, diabetes, and cardiovascular disease.
Among the new evidence, Amgen highlighted a recent independent re-adjudication conducted by the Duke Clinical Research Institute that reaffirmed the drug's noninferiority to a prednisone taper for inducing remission at 26 weeks and found results generally consistent with the original ADVOCATE trial. The submission also cites a meta-analysis of 71 real-world studies involving more than 2,200 patients that reported high remission rates, lower steroid exposure, and improved kidney function, while acknowledging the need for continued liver monitoring due to post-marketing reports of hepatotoxicity. Amgen noted that updated hepatotoxicity warnings and monitoring recommendations were added to the U.S. prescribing information in May.
The company said it looks forward to presenting its case during an FDA hearing, arguing that treatment decisions for patients with rare diseases should reflect the totality of the evidence, including clinical trial data, real-world experience, post-marketing safety information, and patient perspectives. Amgen maintains that Tavneos remains an important therapeutic option for patients with severe active granulomatosis with polyangiitis and microscopic polyangiitis, the two forms of AAV for which the drug is indicated.