The approval will expand the currently approved indication for the prevention of skeletal-related events in patients with bone metastases from solid tumors to also include patients with multiple myeloma.
The FDA has approved denosumab (Xgeva) for the prevention of skeletal-related events in patients with multiple myeloma, announced Amgen.
The approved supplemental Biologics License Application will expand the currently approved indication for the prevention of skeletal-related events in patients with bone metastases from solid tumors to also include patients with multiple myeloma.
"Up to 40% of patients remain untreated for the prevention of bone complications, and the percentage is highest among patients with renal impairment at the time of diagnosis," said Noopur Raje, MD, director, Center for Multiple Myeloma, Massachusetts General Hospital Cancer Center, Boston, in a statement. "Denosumab, which is not cleared through the kidneys, offers multiple myeloma patients bone protection with a convenient subcutaneous administration, providing patients with a novel treatment option."
The approval followed results from the pivotal phase 3 ‘482 study, the largest international multiple myeloma clinical trial ever conducted, according to Amgen. Consisting of 1718 patients, the randomized, double-blind, multicenter study compared denosumab to zoledronic acid for the prevention of skeletal-related events in patients with newly diagnosed multiple myeloma and bone disease.
Participants received either 120 mg of denosumab subcutaneously and placebo intravenously every 4 weeks, or 4 mg of zoledronic acid intravenously and placebo subcutaneously every 4 weeks. The study met the primary endpoint by demonstrating noninferiority of denosumab to zoledronic acid in delaying the time to first on-study skeletal-related event in participants (HR, 0.98; 95% Cl, 0.85, 1.14; P = .01). However, secondary endpoints, delaying time to first skeletal-related event and delaying time to first-and-subsequent skeletal-relate events, did not demonstrate superiority.
Results showed that overall survival was comparable between the 2 drugs (HR, 0.90; 95% Cl, .70-1.16; P = .41). The median difference in progression-free survival (PFS) favored denosumab by 10.7 months (HR, 0.82; 95% Cl, 0.68-0.99; P = .036); the median PFS was 46.1 months for denosumab and 35.4 months for zoledronic acid.
"Bone complications can be devastating for patients with multiple myeloma. Previously, treatment options for the prevention of bone complications were limited to bisphosphonates, which unlike Xgeva, are cleared by the kidneys," said David M. Reese, MD, senior vice president, Translational Sciences and Oncology, Amgen, in a statement. "We are pleased that the FDA has approved the expanded indication for Xgeva, providing a new option for patients and physicians, underscoring our commitment to advancing care for patients with multiple myeloma."