EMA advisors say CSL's Tavneos should be pulled from sale

Pressure is building on Amgen to withdraw rare disease therapy Tavneos, after the EMA's human medicine committee followed the FDA in recommending that its benefits no longer outweigh its risks.

At its June meeting late last week, the CHMP said its review of the pivotal ADVOCATE trial of Tavneos (avacopan) as a treatment for severe, active granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), two rare inflammatory conditions of the blood vessels, has concluded that its approval should be revoked.

Originally developed by ChemoCentryx, which Amgen acquired for $3.7 billion in 2022, Tavneos is licensed by CSL Vifor in Europe. The FDA has been pressuring Amgen to voluntarily withdraw the drug from the US market due to data manipulation concerns in ADVOCATE and potential liver injury risks and, after the company refused, it has started the process to withdraw approval of the drug.

The CHMP has agreed with the FDA's assessment of data integrity in ADVOCATE, saying in a statement that the trial "was conducted in breach of good clinical practice (GCP) principles."

It added: "Study data provided at the time of the assessment of the marketing authorisation application [was] found to be incorrect and misleading and could no longer be relied upon for demonstrating Tavneos' effectiveness."

Moreover, the EMA's advisors have concluded that post-marketing data and other post-hoc analyses of ADVOCATE submitted since then are "not considered sufficient to demonstrate the benefits of the medicine."

If the European Commission confirms the CHMP's recommendation, Tavneos will no longer be authorised in the EU. CSL Vifor, however, has immediately moved to stop all new patient initiations for Tavneos in markets covered by the EMA's jurisdiction.

"While we are disappointed in the outcome of the [review] procedure, we will respect the outcome of the regulatory process and are committed to implementing it in full," said CSL's R&D head, Dr Bill Mezzanotte.

The news will be a massive disappointment to patients with GPA and MPA, two forms of ANCA-associated vasculitis (AAV), which is a group of rare autoimmune diseases that cause inflammation in small blood vessels.

Before the approval of Tavneos, patients with GPA and MPA were typically treated with the anti-CD20 antibody rituximab combined with corticosteroids, a regimen that can have serious side effects when administered over prolonged periods.

Since it was approved in the US in 2021 and the EU in 2022, however, GSK's IL-5 inhibitor Nucala (mepolizumab) has also been approved in some markets, including EU member states and the US, as an add-on treatment for adults with GPA associated with high levels of blood eosinophils.

Global sales of Tavneos were $459 million last year, up 62%, making it an important growth product for Amgen and CSL Vifor.

Photo by Keiron Crasktellanos on Unsplash