Amgen has submitted a supplemental Biologics License Application (sBLA) to the Food and Drug Administration (FDA) for Xgeva (denosumab), to expand it’s indication to the prevention of skeletal-related events (SREs) in patients with multiple myeloma.
Xgeva is already indicated to treat SREs in patients with bone metastases from solid tumors. The sBLA is based on efficacy and safety data from the Phase 3, ‘482 study. A total of 1,718 patients participated and were randomized to receive either subcutaneous Xgeva and intravenous placebo every 4 weeks, or intravenous zoledronic acid and subcutaneous placebo every 4 weeks.
The study met its primary endpoint of Xgeva non-inferiority versus zoledronic acid in delaying the time to first on-study SRE in multiple myeloma patients (HR=0.98, 95% CI: 0.85, 1.14; P=0.01). However, the secondary endpoints of superiority in delaying time to first SRE and first-and-subsequent on-study SRE were not met in the study.
Overall survival (OS) was greater in the Xgeva group compared to the zoledronic acid group, although the difference was not statistically significant (HR=0.90, 95% CI: 0.70, 1.16; P=0.41). The difference in median progression free survival was 10.7 months in favor of Xgeva.
The most common adverse events were diarrhea (33.5% and 32.4% for Xgeva and zoledronic acid, respectively) and nausea (31.5% and 30.4% for Xgeva and zoledronic acid, respectively).
Xgeva is a fully human monoclonal antibody that binds to and neutralizes RANK ligand, and in doing so inhibits osteoclast-mediated bone destruction.
“We look forward to collaborating with regulatory authorities to make Xgeva available to this patient population [multiple myeloma] with an important unmet medical need,” said Sean E. Harper, MD, EVP at Amgen.
For more information visit Xgeva.com.