Treatment of bone lesions in multiple myeloma patients with Amgen’s Xgeva (denosumab) may be expanded to European patients following a positive opinion from the E.U. regulatory entity Committee for Medicinal Products for Human Use (CHMP).
Xgeva is the first fully human antibody that neutralizes the RANKL protein. RANKL plays a key role in the formation, function, and survival of osteoclasts, which are cells that degrade bone. Xgeva is able to prevent the osteoclast-mediated bone breakdown.
In healthy people, osteoclasts participate in bone remodeling, as their bone degradation effect is balanced by replacement with new bone mediated by osteoblasts. However, myeloma patients have overactive osteoclasts and become more prone to bone lesions.
In January 2018, the U.S. Food and Drug Administration extended Xgeva’s approval to include myeloma patients with bone lesions.
Before the recent FDA approval, treating bone lesions in these patients was limited to bisphosphonates, such as Zometa (zoledronic acid). However, these medications are cleared by the kidneys and may cause renal toxicity.
The CHMP’s opinion was based on results from Amgen’s Phase 3 clinical trial (NCT01345019). The study enrolled 1,718 patients randomly assigned to either subcutaneous Xgeva (120 mg) or intravenous zoledronic acid (4 mg).
All patients in the trial had to be planning to receive, or already receiving, primary frontline anti-myeloma therapy.
The patients’ skeletal lesions were assessed with radiography every 12 to 24 weeks.
Trial results showed that Xgeva was at least as good as Zometa at preventing skeletal lesions, while delaying the progression of myeloma by 10.7 months.
The safety profile was in line with known adverse events of Xgeva. Amgen is currently conducting an open-label extension study, where all participants know if they are getting Xgeva or the comparator drug.
“More than 90 percent of patients with multiple myeloma develop bone lesions over the course of the disease. These can result in fractures and other bone complications,” David M. Reese, MD, senior vice president of Translational Sciences and Oncology at Amgen, said in a press release.
“The positive opinion from the CHMP to expand Xgeva’s indication to cover skeletal-related events in patients with multiple myeloma is an important step forward in Amgen’s commitment to improving care for multiple myeloma patients at risk for developing bone complications,” Reese added.
According to Amgen, Xgeva is intended to prevent fracture, spinal cord compression, or the need for radiation or surgery to the bone in myeloma patients and in those with bone metastases from solid tumors.
Before the FDA’s recent approval, the medication was indicated for the treatment of skeletal-related lesions in patients with bone metastases from solid tumors. Amgen is currently pursuing similar approval for myeloma patients from health authorities worldwide.