EU committee urges Tavneos approval for AAV be revoked, drug pulled
Concerns raised over reliability of data on medication's effectiveness
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A committee of the European Medicines Agency has recommended revoking the marketing authorization for Tavneos (avacopan) — an approved oral therapy for ANCA-associated vasculitis (AAV) — in the European Union (EU) over questions about the drug’s effectiveness data.
The recommendation, from the Committee for Medicinal Products for Human Use (CHMP), is now being reviewed by the European Commission, which has final say on all medications available in the EU, with a decision expected shortly. If the CHMP’s recommendation is confirmed, the oral therapy would no longer be available in any EU member state, or in Iceland, Liechtenstein, and Norway.
The move follows a review conducted under an Article 20 nonpharmacovigilance procedure launched at the commission’s request. This type of review is conducted when questions arise about the robustness of available data for a medication.
In the case of Tavneos, issues were raised about how information from ADVOCATE (NCT02994927), the pivotal Phase 3 trial that supported the therapy’s original approval, was handled. Analyses have now confirmed previous concerns that available data “cannot be relied upon to demonstrate the medicine’s effectiveness,” per a statement from the agency. That statement noted that the therapy’s “benefits no longer [are] proven to outweigh [the] risks of treatment.”
Following its recommendation, the CHMP is also urging that no new patients in the EU be started on Tavneos. AAV patients now being treated with the medication are advised to consult their physician and switch to suitable alternatives.
“While we are disappointed in the outcome of the Article 20 procedure, we will respect the outcome of the regulatory process and are committed to implementing it in full,” Bill Mezzanotte, MD, head of research and development at CSL Vifor, which markets the therapy in Europe and other parts of the world, said in a company press release regarding the CHMP’s review.
“Patient care remains our highest priority, and we are working closely with regulatory authorities, healthcare professionals and patient organisations to ensure a compliant and appropriate treatment transition, along with ongoing support for patients,” Mezzanotte said.
In AAV, the immune system mistakenly attacks the body’s own blood vessels, causing inflammation and irreversible organ damage, most often to the kidneys and lungs.
Tavneos is an oral pill designed to block a receptor called C5aR1, which is found on inflammatory cells such as neutrophils, a type of white blood cell that mediates AAV-related damage. By blocking this receptor, the therapy prevents those cells from causing tissue damage.
The drug has been approved in the EU since 2022 to treat adults with severe active granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), the two main types of AAV. It’s used alongside standard treatments, including glucocorticoids or rituximab.
The therapy was originally developed by Chemocentryx and was acquired by Amgen, which sells it in the U.S. In certain countries outside the U.S., commercialization of Tavneos is handled by Vifor Fresenius Medical Care Renal Pharma, a subsidiary of CSL.
FDA also wants Tavneos removed from US market
The pivotal ADVOCATE trial had tested Tavneos against a glucocorticoid plus other standard immunosuppressive agents in more than 300 people with MPA or GPA. The trial met its main goal, with Tavneos at least as effective as glucocorticoids in inducing disease remission. The drug’s use also led to better long-term remission rates than those seen in the control group, researchers said at that time.
However, after reviewing the totality of available data and new information about how the data were handled, the CHMP concluded that the trial did not follow good clinical practice principles. Further, the committee determined that the data provided at the time of the initial assessment were “incorrect and misleading.”
For this reason, no reliable data are available to confirm Tavneos’ effectiveness and, as such, its benefits are no longer proven to outweigh its risks. Available data gathered after the trial concluded and following Tavneos’ approval are also not considered sufficient to demonstrate its benefits, the European Medicines Agency said.
Similar issues with Tavneos have also arisen in the U.S. Before approving Tavneos, the U.S. Food and Drug Administration (FDA) had already expressed concern that the trial design made it difficult to determine what was actually driving the results.
More recently, Amgen declined a FDA request to voluntarily withdraw Tavneos from the U.S. market, noting that the drug’s benefit-risk profile remains favorable based on clinical and real-world data. Still, in April, the FDA’s Center for Drug Evaluation and Research also recommended withdrawing Tavneos from the market.
“We recognise this is a difficult moment for the community, as Tavneos has played an important role for patients living with ANCA-associated vasculitis, a life-threatening disease with limited treatment options,” Mezzanotte said.
Still, in the release, the company stated that “no new patients will be treated with Tavneos in the EU and the European Economic Area.”
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