Positive results from Phase III "482" study shows Xgeva (denosumab) non-inferior to zoledronic acid in delaying skeletal-related event in patients with multiple myeloma .-Amgen

Amgen announced new data from the Xgeva (denosumab) Phase III '482 study, the largest international multiple myeloma trial ever conducted. The study met its primary endpoint, demonstrating Xgeva is non-inferior 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; p=0.01). The analysis demonstrated that patients on Xgeva had a significantly lower rate of renal adverse events compared to zoledronic acid (10.0 percent versus 17.1 percent, p<0.001). These results were presented during an oral session at the 53rd Annual Meeting of the American Society of Clinical Oncology ( ASCO ). The analysis was also selected for the Best of ASCO educational program, which is designed to increase access to practice-changing advances in cancer treatment.

The results presented showed that in patients with renal insufficiency, defined as having a creatinine clearance (CrCl) of less than or equal to 60 mL/min, the rate of renal adverse events was double in the zoledronic acid arm compared to the Xgeva arm (26.4 percent versus 12.9 percent, respectively). The zoledronic acid label does not recommend treatment in patients with a CrCl of less than 30 mL/min; therefore, patients with severe renal impairment were excluded from this study. Median cumulative exposure to Xgeva was 15.75 months compared to 14.78 months for zoledronic acid.

Comment:Xgeva is currently indicated for the prevention of fractures and other skeletal-related events in patients with bone metastases from solid tumors and is the number one prescribedXgeva is currently not indicated for the prevention of skeletal-related events in patients with multiple myeloma. On April 4, 2017 , Amgen announced the submission of a supplemental Biologics License Application to the FDA and an application for a variation to the marketing authorization to the EMA for Xgeva . The submissions to regulatory authorities seek to expand the currently approved Xgeva indication to include patients with multiple myeloma.