Date: 2016-10-20
Type of information: Results
phase: 3
Announcement: results
Company: Amgen (USA - CA) Daiichi Sankyo (Japan)
Product: Xgeva® (denosumab)
Action
mechanism: monoclonal antibody. Denosumab is a fully human monoclonal antibody that binds to RANK Ligand, a protein essential for the formation, function and survival of osteoclasts (the cells that break down bone). Xgeva® prevents RANK Ligand from activating its receptor, RANK, on the surface of osteoclasts, thereby decreasing bone destruction.
Disease: skeletal-related event (SRE) in patients with multiple myeloma
Therapeutic area: Cancer - Oncology - Bone diseases
Country: Australia, Austria, Bulgaria, Canada, Czech Republic, France, Germany, Greece, Hong Kong, Hungary, Ireland, Italy, Japan, Republic of Korea, Lithuania, Malaysia, New Zealand, Poland, Portugal, Russian Federation, Singapore, Slovakia, Spain, Switzerland, Taiwan, Turkey, Ukraine, UK, USA
Trial
details: The '482 study was an international, randomized, double-blind, multicenter trial of Xgeva® compared with zoledronic acid in the prevention of bone complications in patients with newly diagnosed multiple myeloma. In the study, a total of 1,718 patients (859 on each arm) were randomized to receive either subcutaneous Xgeva® 120 mg and intravenous placebo every four weeks, or intravenous zoledronic acid 4 mg (adjusted for renal function) and subcutaneous placebo every four weeks. The primary endpoint of the study was non-inferiority of Xgeva® versus zoledronic acid with respect to time to first on-study SRE (fracture, radiation to bone, surgery to bone or spinal cord compression). Secondary endpoints included superiority of Xgeva® versus zoledronic acid with respect to time to first on-study SRE and first-and-subsequent on-study SRE and overall survival.The safety and tolerability of Xgeva® were also compared with zoledronic acid. (NCT01345019)
Latest
news: * On October 20, 2016, Amgen announced that a Phase 3 study evaluating Xgeva® (denosumab) versus zoledronic acid met the primary endpoint of non-inferiority (hazard ratio = 0.98, 95 percent CI, 0.85 - 1.14) in delaying the time to first on-study skeletal-related event (SRE) in patients with multiple myeloma. The secondary endpoints of superiority in delaying time to first SRE and delaying time to first-and-subsequent SRE were not met. The hazard ratio of Xgeva® versus zoledronic acid for overall survival was 0.90 (95 percent CI, 0.70 - 1.16).
Adverse events observed in patients treated with Xgeva® were generally consistent with the known safety profile of Xgeva®. The most common adverse events (greater than 25 percent) in the Xgeva® arm of the study were diarrhea and nausea.
