Amgen Dismisses FDA Request to Withdraw Tavneos

Amgen is pushing back against an FDA request asking it to voluntarily withdraw its vasculitis drug Tavneos (avacopan) from the U.S. market due to concerns related to clinical trial adjudication and liver safety. In an Amgen notice to healthcare providers, the company says it has no plans to withdraw the 2021-approved drug and is working with the agency to determine a path forward.

Tavneos is approved as an adjunctive treatment for adults with severe active anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV), including granulomatosis with polyangiitis and microscopic polyangiitis, in combination with standard therapy that includes glucocorticoids. The drug was developed by ChemoCentryx, which Amgen acquired in 10/2022.

“Hepatotoxicity, which is a known infrequent risk of Tavneos treatment for AAV, was also raised in the context of the benefit-risk profile of the medicine,” the company says. “Amgen is not aware of any issues with the underlying patient data and after review of the relevant clinical data and years of real-world evidence, Amgen is confident that Tavneos demonstrates effectiveness and a favorable benefit-risk profile."

Amgen says that in the pivotal ADVOCATE trial that was submitted to gain approval, Tavneos met the primary endpoint of noninferiority to a prednisone taper in achieving remission at 26 weeks, with remission rates of 72.3% in the Tavneos arm compared with 70.1% in the prednisone arm. The drug was also superior in sustaining remission at 52 weeks, with rates of 65.7% versus 54.9%, respectively.

Amgen also points to an integrated safety analysis of two Phase 2 trials and the ADVOCATE study, which included 239 patients treated with avacopan and 200 patients who did not receive the drug. The analysis showed lower exposure-adjusted rates of adverse events and serious adverse events in the avacopan group compared with the control group.

Amgen says it continues to conduct FDA-required post-marketing studies, as well as U.S. and international real-world observational studies, to further characterize the drug’s safety and effectiveness. Additional studies in Europe and Japan are prospectively monitoring patients receiving Tavneos for safety events.

While most companies ultimately comply with an FDA request for voluntary withdrawal, there are several notable cases where sponsors initially refused, delayed, or publicly contested the agency’s position. Outcomes have varied, but the agency retains strong leverage.

Most recently, FDA sought the withdrawal of Covis Pharma’s Makena (hydroxyprogesterone caproate), indicated for reducing the risk of pre-term birth in women with a singleton pregnancy, after a required confirmatory trial (PROLONG) failed to show benefit. Covis, too, refused to voluntarily withdraw Makena for several years and continued marketing while pursuing regulatory appeals. After prolonged administrative proceedings, FDA ordered the withdrawal in 2023.