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FDA rejects Amgen's Xgeva sBLA for prevention of bone metastases

Friday, April 27 2012 | Comments
Evidence Grade 0 What's This?
Amgen Inc. received a complete response letter from the Food and Drug Administration regarding the supplemental Biologics License Application (sBLA) for Xgeva (denosumab) to treat men with castration-resistant prostate cancer who are at high risk for developing bone metastases. 

The FDA said it could not approve the application in its present form. According to Amgen, the regulatory agency determined that Xgeva's effect on bone metastases-free survival (BMFS) was of insufficient magnitude to outweigh the drug's risks, including osteonecrosis of the jaw, in the intended population.

FDA officials requested data from "an adequate and well-controlled trial(s) demonstrating a favorable risk-benefit profile for Xgeva that is generalizable to the U.S. population," Amgen noted.

In February, The Associated Press reported that the FDA's Oncologic Drugs Advisory Committee voted 12-1 against recommending approval of the additional indication for Xgeva.

The panel referred to data from a clinical study that was used to support the Xgeva sBLA. In the 1,432-patient, Phase III trial of men with castration-resistant prostate cancer who did not have bone metastases at baseline, treatment with Xgeva significantly prolonged BMFS by a median of 4.2 months relative to placebo (29.5 months vs. 25.2 months, respectively).

However, osteonecrosis of the jaw was reported more frequently with Xgeva than with placebo.

Also, there was no difference between the two groups in overall survival (OS), although Amgen noted that the trial was not designed to show an OS benefit with Xgeva.

The committee concluded that the "statistical benefit" observed with Xgeva in BMFS did not translate into a meaningful benefit for patients and that the benefits did not outweigh the risks, according to the AP.

"We are reviewing the complete response letter and will work with [the] FDA to determine any next steps," said Dr. Sean Harper, Amgen's executive vice president of research and development. "The FDA's action today does not impact the approved indication of XGEVA in the prevention of skeletal-related events in men with bone metastases from prostate cancer, which was acknowledged by the FDA and the advisory committee members who discussed the application."

Specifically, Xgeva is currently approved for the prevention of skeletal-related events in patients with bone metastases from solid tumors.

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