FDA Grants Approval for Denosumab in the Prevention of Skeletal-Related Events in Patients With Multiple Myeloma
Today, the U.S. Food and Drug Administration approved the supplemental Biologics License Application for denosumab (Xgeva) to expand the currently approved indication in the prevention of skeletal-related events in patients with bone metastases from solid tumors to include patients with multiple myeloma.
The approval was based on data from the phase III 482 study, which compared zoledronic acid and denosumab in the ability to delay skeletal-related events for those being treated for multiple myeloma. The study included 1718 patients with newly diagnosed multiple myeloma, with half in each treatment arm.
The study met the primary endpoint, demonstrating noninferiority of denosumab to zoledronic acid in delaying the time to first on-study skeletal-related event in patients with multiple myeloma. The secondary endpoints, delaying the time to first skeletal-related event and delaying the time to first and subsequent skeletal-related events, did not demonstrate superiority.
Overall survival was comparable between the two treatments, with a hazard ratio of 0.90. The median difference in progression-free survival favored denosumab by 10.7 months, with a median progression-free survival of 46.1 months with denosumab and 35.4 months with zoledronic acid.
Adverse events observed in patients treated with denosumab were generally consistent with its known safety profile. The most common adverse reactions (≥ 10%) were diarrhea (34%), nausea (32%), anemia (22%), back pain (21%), thrombocytopenia (19%), peripheral edema (17%), hypocalcemia (16%), upper respiratory tract infection (15%), rash (14%), and headache (11%).