Photo by Bill Branson
Vials of drug
The European Commission (EC) has approved an expanded indication for denosumab (Xgeva).
The drug is now approved for the prevention of skeletal-related events (SREs) in adults with advanced malignancies involving bone, which includes patients with multiple myeloma (MM).
Approval from the EC provides a centralized marketing authorization with unified labeling in all member countries of the European Union.
Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.
Denosumab was previously approved by the EC to prevent SREs—defined as radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression—in adults with bone metastases from solid tumors.
Denosumab also received EC approval for the 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.
The EC’s approval for denosumab in MM patients is based on data from the ’482 study, which were recently published in The Lancet Oncology.
In this phase 3 trial, denosumab proved non-inferior to zoledronic acid for delaying SREs in patients with newly diagnosed MM and bone disease.
Researchers randomized 1718 patients to receive subcutaneous denosumab at 120 mg and intravenous placebo every 4 weeks (n=859) or intravenous zoledronic acid at 4 mg (adjusted for renal function at baseline) and subcutaneous placebo every 4 weeks (n=859).
All patients also received investigators’ choice of first-line MM therapy.
The median time to first on-study SRE was 22.8 months for patients in the denosumab arm and 24 months for those in the zoledronic acid arm (hazard ratio=0.98; 95% confidence interval: 0.85-1.14; P for non-inferiority=0.010).
There were fewer renal treatment-emergent adverse events in the denosumab arm than the zoledronic acid arm—10% and 17%, respectively.
But there were more hypocalcemia adverse events in the denosumab arm than the zoledronic acid arm—17% and 12%, respectively.