Phase III study '482' published in The Lancet Oncology for Xgeva for prevention of skeletal-related events in multiple myeloma patients.- Amgen.

Amgen announced results from the Xgeva (denosumab) Phase III '482 study, the largest international multiple myeloma trial for the prevention of skeletal-related events ever conducted (n=1,718), were published in The Lancet Oncology. In this study, Xgeva successfully met the primary endpoint, demonstrating non-inferiority to zoledronic acid in delaying the time to first on-study skeletal-related event in patients with multiple myeloma (HR=0.98, 95 percent CI: 0.85-1.14). The median time to first on-study skeletal-related event was 22.8 months for Xgeva and 24 months for zoledronic acid. Approximately 60 percent of all first skeletal-related events occurred within the first three months, and 81 percent occurred within the first six months. Overall survival, a secondary endpoint of the study, was similar between the Xgeva and zoledronic acid arms, with a hazard ratio of 0.90 (95 percent CI: 0.70-1.16). Progression-free survival, an exploratory endpoint not powered for statistical significance, was 46.1 months (95 percent CI: 34.3 months-not estimable [NE], n=219) for Xgeva and 35.4 months (95 percent CI: 30.2 months-NE, n=260) for zoledronic acid on top of standard of care anti-myeloma therapy.

The safety profile was consistent with known adverse events of both Xgeva and zoledronic acid. There were fewer renal treatment-emergent adverse events in the Xgeva arm compared to the zoledronic acid arm (10 percent versus 17 percent, respectively). Hypocalcaemia events were higher in the Xgeva arm compared to the zoledronic acid arm (17 percent versus 12 percent, respectively). Osteonecrosis of the jaw was observed in 4 percent of the XGEVA-treated patients versus 3 percent of the zoledronic acid-treated patients. The most common treatment-emergent adverse events (greater than 25 percent) were diarrhea and nausea.