FDA points to liver injury with Amgen's Tavneos

The FDA has ramped up the pressure on Amgen to withdraw Tavneos for a rare vasculitis condition from the market, with a report saying it has identified cases of serious liver injury – including deaths – among people taking the drug.

A new drug safety communication from the US regulator, which asked Amgen to suspend sales of Tavneos (avacopan) in January, indicates it has found 76 cases of drug-induced liver injury (DILI) from around the world that it says have "reasonable evidence of a causal association" with the product. The tally included 54 hospitalisations and eight deaths, and the vast majority (66) of cases were reported in Japan.

There were seven cases of a serious liver reaction in which the bile ducts are destroyed, known as vanishing bile duct syndrome (VBDS), which the FDA also thinks may be related to the use of Tavneos. All the patients who developed VBDS were hospitalised, and there were three fatalities.

It is recommending extensive liver panel testing in patients taking the drug for the first five months of treatment, with prompt discontinuation of dosing if liver damage biomarkers or DILI symptoms such as jaundice are seen.

Tavneos has been approved in the US since 2021 and is used to treat two forms of ANCA-associated vasculitis, granulomatosis with polyangiitis (GPA), or microscopic polyangiitis (MPA). It is one of Amgen's fastest-growing drugs, with sales growing 62% last year to reach $459 million.

Amgen added the oral complement C5 inhibitor to its portfolio in 2022 when it bought ChemoCentryx in a $3.7 billion deal.

The FDA has characterised the DILI and VBDS as new safety concerns with Amgen's product, but the drugmaker has said that liver toxicity – including VBDS – is "a known infrequent risk of Tavneos treatment."

So far, it has denied the FDA's request to suspend distribution of the medicine, saying it is still "confident that Tavneos is an important and effective medicine for severe ANCA-associated vasculitis based on robust clinical data and real-world evidence demonstrating the effectiveness and favourable benefit–risk profile."

In the EU, the EMA also started a review of Tavneos in January, in response to what it said were concerns about 'data integrity' in the ADVOCATE trial, run by ChemoCentryx, that supported regulatory approvals.

In its fourth-quarter update, Amgen said it was "not aware of any issue with the underlying patient data from the ChemoCentryx clinical trial."

Prior to 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.

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 elevated blood eosinophils.