Amgen files sBLA with FDA and application for variation of MAA with EMA for Xgeva (denosumab) to prevent skeletal-related events (SREs) in solid tumors to include patients with multiple myeloma.-Amgen

Amgen has announced the submission of a supplemental Biologics License Application (sBLA) to the FDA and an application for a variation to the marketing authorization to the European Medicines Agency (EMA) for Xgeva (denosumab). The submissions to regulatory authorities seek to expand the currently approved Xgeva indication for the prevention of skeletal-related events (SREs) in solid tumors to include patients with multiple myeloma.

The applications include new data from the pivotal Phase III head-to-head '482 study, the largest international multiple myeloma trial ever conducted. Xgeva is currently indicated for the prevention of SREs in patients with bone metastases from solid tumors based on results from three previous pivotal Phase III head-to-head studies. In these Phase III studies,Xgeva demonstrated superiority in the solid tumors studied compared to zoledronic acid. In the U.S., Xgeva has a limitation of use noting that it is not indicated for the prevention of SREs in patients with multiple myeloma.

The sBLA is based on efficacy and safety data from the pivotal Phase III '482 study, which demonstrated that Xgeva is non-inferior to zoledronic acid in delaying the time to first on-study SRE in patients with multiple myeloma (HR=0.98, 95 percent CI: 0.85, 1.14; p=0.01). The secondary endpoints of superiority in delaying time to first SRE and delaying time to first-and-subsequent SRE were not met in this study. Overall survival (OS), another secondary endpoint, was also in favor of Xgeva over zoledronic acid (HR=0.90, 95 percent CI: 0.70, 1.16; p=0.41); however, it was not statistically significant. The hazard ratio of Xgeva versus zoledronic acid for progression-free survival (PFS) was 0.82 (95 percent CI: 0.68, 0.99; descriptive p=0.036). The median PFS difference between arms was 10.7 months in favor of Xgeva. These results were presented during the late-breaking abstract session at the 16th International Myeloma Workshop.