Amgen has announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion to expand the current indication for XGEVA® (denosumab) to cover skeletal-related events in patients with multiple myeloma.
If approved, XGEVA will be indicated for the prevention of skeletal-related events in adults with advanced malignancies involving bone. The application included new data from the Phase 3 ‘482 study, the largest international multiple myeloma trial for the prevention of skeletal-related events ever conducted.
In the ‘482 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% CI: 0.85-1.14). The median time to first on-study skeletal-related event was 22.83 months for XGEVA and 23.98 months for zoledronic acid. The safety profile was consistent with known adverse events of XGEVA.
“More than 90% of patients with multiple myeloma develop bone lesions over the course of the disease. These can result in fractures and other bone complications,” said David M Reese, MD, senior vice president of Translational Sciences and Oncology at Amgen. “The positive opinion from the CHMP to expand XGEVA’s indication to cover skeletal-related events in patients with multiple myeloma is an important step forward in Amgen’s commitment to improving care for multiple myeloma patients at risk for developing bone complications.”
Bone complications, also known as skeletal-related events, are defined as radiation to bone, pathologic fracture, surgery to bone and spinal cord compression.1
XGEVA is the first fully human monoclonal antibody that binds to and neutralises RANK ligand (RANKL) – a protein essential for the formation, function and survival of osteoclasts, cells which break down bone – thereby inhibiting osteoclast-mediated bone destruction. On 5 Jan 2018, the US Food and Drug Administration (FDA) approved the supplemental Biologics License Application (sBLA) for XGEVA to expand the currently approved indication for the prevention of skeletal-related events in patients with bone metastases from solid tumors to include patients with multiple myeloma. Additional regulatory applications for XGEVA for the prevention of skeletalrelated events in patients with multiple myeloma are underway and have been submitted to health authorities worldwide.
Following the CHMP positive opinion, the centralised European marketing authorisation of XGEVA will be expanded to cover the multiple myeloma patient population. Norway, Iceland and Liechtenstein, as members of the European Economic Area (EEA), will take corresponding decisions on the basis of the decision of the European Commission.
- Roodman GD. Pathogenesis of myeloma bone disease. Leukemia. 2009;23(3):435–441