FDA turns down new use for Amgen's Xgeva

The US Food and Drug Administration (FDA) has rejected a bid by Amgen to expand the labelling for its Xgeva (denosumab) product, following the advice of its advisory committee earlier this year.

Amgen had sought to win approval for the use of Xgeva to prevent bone metastases in patients with castration-resistant prostate cancer, in addition to its current indication to prevent cancer-related bone injuries which was given the go-ahead in 2010.

The FDA has said in its Complete Response Letter however that it cannot approve the new use without an additional clinical trial. 

The FDA's decision is not surprising, given that the Oncologic Drugs Advisory Committee (ODAC) voted by 12 to one in February that the benefits of Xgeva in preventing bone metastases do not outweigh the risks of therapy.

The panel said at the time they were concerned that while Xgeva reduced the risk of bone metastases forming by around 15 per cent in a phase III trial, there was no benefit in terms of survival or alteration in the course of the disease.

Given that there was a 5 per cent risk that patients on Xgeva could develop bone-related complications, notably osteonecrosis of the jaw, the panel decided against recommending approval.

Amgen's head of R&D Sean Harper said that the company was reviewing the CRL to "determine any next steps" for Xgeva in this setting.

The letter said that the FDA required data from "adequate and well controlled trial(s) demonstrating a favourable risk-benefit profile for Xgeva that is generalisable to the US population".

The news is a blow to Amgen, as Xgeva is a growth product for the firm at a time when it is facing declining sales for its big-selling red cell boosters Epogen (epoetin alfa) and Aranesp (darbepoetin alfa).

Xgeva brought in $351m for the company in 2011 and added another $153m in the first quarter of 2012, more than three times the tally a year earlier.

Analysts said they had already discounted any contribution from a bone metastasis indication for the drug, and many still believe it can generate sales in excess of $1bn at peak.

Meanwhile, Amgen is also carrying out clinical trials of Xgeva to see if it can prevent bone metastases in other cancer types.