Xgeva regulatory update

FDA's Oncologic Drugs Advisory Committee voted 12-1 that Xgeva denosumab from Amgen does not have a favorable benefit-risk profile to prevent bone metastases in men with castration-resistant prostate cancer (CRPC). The panel did not feel that the 4.2-month improvement in bone metastasis-free survival (BMFS) vs. placebo seen in the Phase III 147 study was clinically meaningful, especially since Xgeva did not show improvement in overall survival (OS), progression-free survival (PFS) or quality of life. Panelists also felt the approximate 5% incidence of osteonecrosis of the jaw (ONJ) was too much of a risk for asymptomatic patients (see BioCentury, May, 23, 2011 & Feb. 6, 2012).

The panel agreed that data show the cumulative risk of ONJ increases with exposure to Xgeva, but the drug's benefits across the continuum of prostate cancer disease states is unknown. The sBLA for the indication is under FDA review with an April 26 PDUFA date. Xgeva is approved in the U.S. and EU to prevent skeletal related events (SREs) in adults with bone metastases from solid tumors. The drug is also approved as Prolia in the U.S. and EU to treat osteoporosis in postmenopausal women and in the EU to treat bone loss associated with hormone ablation in men with prostate cancer. An sBLA for Prolia to increase bone mass in men with osteoporosis at high risk for fracture is also under FDA review with a Sept. 20 PDUFA date. ...