FDA Approves Denosumab Bone Strengthener for Myeloma Patients

Amgen's new bone strengthener denosumab (XGEVA®) received FDA approval today for patients with multiple myeloma based on data from the largest myeloma clinical trial ever conducted. Denosumab was previously approved for solid tumors but was used in a Phase III multiple myeloma study that included 1718 patients. The new drug is particularly helpful for patients with kidney (renal) issues and is conveniently given as a shot and not as an IV administration.

"Up to 40 percent 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, M.D., director, Center for Multiple Myeloma, Massachusetts General Hospital Cancer Center, Boston. "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."

XGEVA is a fully human monoclonal antibody that binds to and neutralizes RANK ligand (RANKL) – a protein essential for the formation, function and survival of osteoclasts, which break down bone – thereby inhibiting osteoclast-mediated bone destruction. XGEVA is currently the number one prescribed bone-targeting agent in the U.S. for the prevention of skeletal-related events in patients with bone metastases from solid tumors. Additional regulatory applications for XGEVA for the prevention of skeletal-related events in patients with multiple myeloma are underway and have been submitted to health authorities worldwide. The drug was compared to Zometa (zoledronic acid) in the '482 study that involved 1,781 patients (859 in each study arm). Patients received either subcutaneous XGEVA 120 mg and IV placebo every four weeks or IV zoledronic acid 4 mg (adjusted for renal function) and subcutaneous placebo every four weeks. XGEVA was found to have the same impact as zoledronic acid. Overall survival was comparable between XGEVA and zoledronic acid. When progression free survival was compared, XGEVA was superior at 46.1 months compared to zoledronic acid's 35.4 months. Osteonecrosis of the jaw is a known side effect of bone strentheners. In the '482 study, ONJ was confirmed in 4.1% of XGEVA patients and 2.8% of zoledronic acid patients. More than 90 percent of patients develop bone (osteolytic) lesions during the course of the disease. Preventing bone complications is a critical aspect of caring for patients with multiple myeloma, because these events can cause significant pain and impact morbidity.  

"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, M.D., senior vice president of Translational Sciences and Oncology at Amgen. "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."

Approximately 60 percent of all multiple myeloma patients have or will develop renal impairment over the course of the disease, so this is a welcome option to help protect their bones while preserving their kidneys.