Amgen submits applications in the US and Europe to expand current indication for Xgeva

Applications include data from the largest international trial conducted in multiple myeloma.

Amgen has submitted a supplemental Biologics License Application (sBLA) to the FDA and an application for a variation to the marketing authorization to the EMA for Xgeva (denosumab). The submissions to regulatory authorities seek to expand the currently approved Xgeva indication for the prevention of skeletal-related events (SREs) in solid tumours to include patients with multiple myeloma. The applications include new data from the pivotal Phase III head-to-head '482 study, the largest international multiple myeloma trial ever conducted.

Xgeva is a fully human monoclonal antibody that binds to and neutralizes RANK ligand (RANKL) - a protein essential for the formation, function and survival of osteoclasts, which break down bone - thereby inhibiting osteoclast-mediated bone destruction. Xgeva is currently indicated for the prevention of SREs in patients with bone metastases from solid tumors based on results from three previous pivotal Phase III head-to-head studies. In these Phase III studies, Xgeva demonstrated superiority in the solid tumours studied compared to zoledronic acid. In the US, Xgeva has a limitation of use noting that it is not indicated for the prevention of SREs in patients with multiple myeloma.

"Bone lesions are a hallmark of multiple myeloma and often result in bone complications, which can be devastating for patients. Current treatment options for bone complications are limited to bisphosphonates, which are associated with renal toxicity. Approximately 60% of all multiple myeloma patients have or will develop renal impairment over the course of the disease," said Sean E. Harper, executive vice president of R&D at Amgen. "Xgeva's unique mechanism of action may offer multiple myeloma patients a novel treatment option that is not renally cleared. We look forward to collaborating with regulatory authorities to make Xgeva available to this patient population with an important unmet medical need."

The sBLA is based on efficacy and safety data from the pivotal Phase III '482 study, which demonstrated that Xgeva is non-inferior to zoledronic acid in delaying the time to first on-study 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 in this study. Overall survival (OS), another secondary endpoint, was also in favour of Xgeva over zoledronic acid; however, it was not statistically significant. The hazard ratio of Xgeva versus zoledronic acid for progression-free survival (PFS) was 0.82. The median PFS difference between arms was 10.7 months in favour of Xgeva. These results were presented during the late-breaking abstract session at the 16th International Myeloma Workshop.