FDA panel votes that benefits of Amgen's Xgeva don't outweigh risks in patients with prostate cancer

An FDA panel on Wednesday voted 12-1 that the benefits of Amgen’s Xgeva (denosumab) did not outweigh its risks in patients with castrate-resistant prostate cancer (CRPC). "The effect of the studied compound is quite weak with no effect on survival or the overall course of the disease in general," commented panelist Ronald Richardson.

In staff documents released ahead of the meeting, agency staff said that while the drug appeared to reduce the risk of developing bone metastases in a late-stage study involving patients with CRPC, it did not increase overall survival and carries significant side effects.

At the meeting, panelists termed evidence that patients taking Xgeva experienced a four-month delay in the spread of cancer to the bones as a "statistical benefit," but not one that resulted in increased survival or higher quality of life for patients. Panel chair Wyndham Wilson remarked that "if it was one year we probably wouldn’t even be here today, no one is denying that, but the magnitude here is quite low."

Panel members also expressed concern about the drug’s safety profile, including osteonecrosis of the jaw in about 5 percent of the 1432 patients studied. In addition, staff questioned whether the drug may "shift the pattern of metastases to non-bony areas." Wilson said that the drug’s risk make it safer for patients to continue only taking Xgeva when tumours already have spread to their bones. "This isn't a question of whether this drugs works. The question is when is the most effective time to give it," he added.

Amgen said that it would continue discussions with the FDA regarding its filing. CMO Sean Harper noted that "the development of bone metastasis is an irreversible, life-changing event for men living with castration-resistant prostate cancer and is associated with significant and progressive morbidity," adding that "Xgeva is the first agent to prolong bone metastasis-free survival and addresses this important unmet medical need."

A final decision is expected by April 26. Xgeva and Prolia had combined sales of approximately $550 million last year. BMO Capital Markets analyst Jim Birchenough forecast that Xgeva sales would reach between $3 billion and $4 billion in 2015, and suggested that if the company fails to win approval in the pending prostate cancer indication, the lost potential revenue would be about $1 billion.

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