482 Phase III study shows Xgeva (denosumab) non inferior to zoledronic acid in the prevention of bone complications in patients with newly diagnosed multiple myeloma.-Amgen

The 482 study was an international, Phase III, randomized, double-blind, multicenter trial of Xgeva (denosumab)compared with zoledronic acid in the prevention of bone complications in patients with newly diagnosed multiple myeloma.

Amgen announced positive data from the Phase III 482 study, the largest international multiple myeloma trial ever conducted. In this study, Xgeva (denosumab) met the primary endpoint, demonstrating non-inferiority to zoledronic acid in delaying the time to first on-study skeletal-related event (SRE) in patients with multiple myeloma (HR=0.98, 95 percent CI: 0.85, 1.14; p=0.01). The median time to first on-study SRE was similar between Xgeva (22.83 months) and zoledronic acid (23.98 months). These data will be presented during the late-breaking abstract session at the 16th International Myeloma Workshop (IMW) in New Delhi.

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. There was a suggested trend in overall survival (OS) 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. Adverse events observed in patients treated with XgevaA were consistent with the known safety profile of Xgeva. The most common adverse events (greater than 25 percent) were diarrhea (33.5 percent Xgeva and 32.4 percent zoledronic acid) and nausea (31.5 percent Xgeva and 30.4 percent zoledronic acid).