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 per cent 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 per cent 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.
"Bone complications like fracture, spinal cord compression and radiation or surgery to bone are devastating for multiple myeloma patients. Many of these patients suffer from renal impairment, which has limited their treatment options," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Xgeva's unique mechanism of action has the potential to prevent bone complications in multiple myeloma patients regardless of their renal status, fulfilling an important unmet medical need."
Detailed results will be submitted to a future medical conference and for publication. The company plans to submit these data to regulatory authorities.
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.
Multiple myeloma is the second most common hematologic cancer, and it develops in plasma cells located in the bone marrow. Each year an estimated 114,000 new cases of multiple myeloma are diagnosed worldwide, resulting in more than 80,000 deaths per year.
Bone lesions frequently accompany multiple myeloma and can increase the risk of bone complications. Approximately 75 per cent of multiple myeloma patients are treated for the prevention of bone complications. Preventing bone complications is an important aspect of caring for patients with multiple myeloma, because these events can cause significant morbidity.
Xgeva targets the RANK ligand pathway to prevent the formation, function and survival of osteoclasts, which break down bone. Xgeva is indicated for the prevention of SREs in patients with bone metastases from solid tumors and for treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity. Xgeva is also indicated in the US for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy. Xgeva is not indicated for the prevention of skeletal-related events in patients with multiple myeloma.