Regulatory pressure is mounting on Amgen’s inflammatory disorder drug, Tavneos, with the European Medicines Agency recommending revocation of the product’s approval in its territory. The move follows an FDA proposal to pull U.S. approval of the product due to safety risks and alleged manipulation of clinical trial data.
The Committee for Medicinal Products for Human Use (CHMP), an EMA body, conducted its own review of Tavneos. On Friday, the agency said this review concluded that the drug’s “benefits are no longer proven to outweigh its risks.” The committee is now recommending that clinicians do not start new patients on treatment with the drug and that patients currently taking this once-daily pill be switched to alternative therapies. The CHMP recommendations must be adopted by the European Commission before Tavneos’s European marketing authorization can be formally withdrawn.
While Amgen markets Tavneos in the U.S., its rights in the rest of world, including Europe, are held by Vifor Fresenius Medical Care Renal Pharma, a subsidiary of CSL Limited. Kissei Pharmaceutical holds rights to the drug in Japan under a sublicense from Vifor.
Tavneos is an oral small molecule designed to block C5a, a receptor found in the complement system, a part of the immune system. This drug was originally developed by ChemoCentryx, a biotech company that Amgen acquired in 2022. Under ChemoCentryx, Tavneos had received FDA approval for treating antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, a group of inflammatory disorders that causes inflammation leading to blood vessel and organ damage. The EMA’s 2022 marketing authorization is narrower, covering severe active granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), two subsets of ANCA-associated vasculitis, sometimes shortened to AAV.
The steroids that are a standard treatment for ANCA-associated vasculitis come with a range of risks, particularly with long-term use. Tavneos does not replace steroid treatment, but the drug enables patients to reduce their reliance on steroids with a drug that takes a different approach to counteracting inflammation.
The CHMP started its review of Tavneos in late January, shortly after the FDA asked Amgen to voluntarily withdraw the product from the U.S. market. Of particular concern to the FDA were reports of severe liver injury, mostly cases in Japan. The FDA also expressed concerns about the handling of clinical data prior to Tavneos’s regulatory approval, concerns that are now echoed by the CHMP.
In its announcement of its Tavneos recommendation, the CHMP said its review of the available data and new information about how clinical trial data were handled led the committee to conclude that the pivotal study, named Advocate, was conducted in breach of good clinical practice principles.
“Study data provided at the time of the assessment of the marketing authorisation application were found to be incorrect and misleading and could no longer be relied upon for demonstrating Tavneos’ effectiveness,” the CHMP said. “Supportive post-marketing data and other post-hoc analyses of the Advocate study are not considered sufficient to demonstrate the benefits of the medicine.”
The CHMP’s conclusions regarding Tavneos are similar to those of the FDA, which in April proposed a withdrawal of the drug from the U.S. market. The FDA’s procedure gives a drug company the opportunity to request a hearing, which Amgen has done. A June 29 deadline for submission of supporting materials for this hearing has been extended by a month.
In an emailed statement, Amgen said it is “deeply concerned” about the potential impact the CHMP recommendation could have on the ability for patients to access Tavneos as a treatment option that can reduce exposure to steroids.
“Amgen continues to believe that Tavneos is an important treatment option for people living with AAV with a favorable benefit-risk profile based on all available data including over 20 real-world studies,” the company said. “The deadline for our hearing submission has been extended to July 29, and we remain engaged with the FDA as the regulatory process continues in the United States.”
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