FDA Approves New Multiple Myeloma Indication for Denosumab

Recently, Amgen announced that the FDA approved the supplemental biologics application for denosumab (Xgeva) for the prevention of skeletal-related events among patients with multiple myeloma (MM) who have developed bone metastases, according to a press release.

Denosumab is a fully human monoclonal antibody that binds to the RANK ligand (RANKL), which inhibits osteoclast-mediated bone destruction, according to the release. The new approval expands the current indication of denosumab for preventing skeletal events among patients with solid tumors that have metastasized to the bone.

"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. "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 expanded indication is based on positive findings from the phase three ‘483 clinical trial, which enrolled 1718 patients with newly-diagnosed MM. Patients were randomized to receive either subcutaneous denosumab 120-mg and intravenous (IV) placebo or IV zoledronic acid 4-mg and subcutaneous placebo every 4 weeks.

The primary endpoint was to evaluate non-inferiority of denosumab versus zoledronic acid determined by first on-study skeletal-related events, such as pathologic fracture, radiation to bone, surgery to bone, or spinal cord compression, according to the release. Secondary endpoints included superiority of denosumab and overall survival.

The researchers found that the study met the primary endpoint, but did not meet the secondary endpoint of delaying time to first and subsequent skeletal events; however, overall survival was comparable for both treatments.

The investigators found that the median progression-free survival for patients treated with denosumab was 35.4 months compared with 46.1 months for zoledronic acid, a difference of 10.7 months, according to the release.

Common adverse events for denosumab were consistent and included nausea, anemia, back pain, thrombocytopenia, peripheral edema, hypocalcemia, upper respiratory tract infection, rash, and headache.

According to Amgen, denosumab is the top prescribed bone-targeting drug for preventing skeletal-related events for patients with bone metastases from solid tumors.

Additional supplemental indication applications are still being reviewed, according to the release.

"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."