Xgeva Gains Europe’s Approval for Preventing Bone Lesions in Multiple Myeloma

The European Commission has extended Xgeva‘s (denosumab) approval for the prevention of bone lesions in multiple myeloma patients, Amgen, the medicine’s maker, announced.

The injectable therapy, which already was approved for patients with bone metastases from solid tumors, is now indicated for the prevention of lesions in adults with advanced malignancies involving bone.

In January, the U.S. Food and Drug Administration also extended Xgeva’s approval to include myeloma patients with bone lesions.

That approval was based on data from the Phase 3 clinical rial (NCT01345019), conducted to determine if Xgeva could prevent bone lesions in multiple myeloma patients at least as good as the standard care.

A process called bone remodeling is key to keeping normal bones strong and healthy. In the process, special cells called osteoclasts break down old bone, while osteoblasts replace it with new one.

Patients with multiple myeloma, however, have overactive osteoclasts, and become more prone to developing bone lesions. Currently, treatment options for multiple myeloma patients are limited to bisphosphonates. But these are cleared by the kidneys and are associated with renal toxicity.

Xgeva is a monoclonal antibody that neutralizes the activity of the RANK ligand (RANKL), a protein essential for the formation and function of osteoclasts. By inhibiting bone destruction caused by osteoclasts, Xgeva prevents bone lesions. And because it is not cleared through the kidneys, it is expected to have fewer adverse effects.

The Phase 3 study compared Xgeva with zoledronic acid — a kind of biphosphonate — in the prevention of bone lesions in adult patients with newly diagnosed multiple myeloma and bone disease.

A total of 1,718 patients were chosen at random to receive either subcutaneous Xgeva plus an intravenous placebo, or intravenous Zometa plus subcutaneous placebo, every four weeks. This was given along with first-line anti-myeloma therapy chosen by the investigators.

Bone analysis using X-rays were performed every 12 to 24 weeks.

Xgeva was found to be at least as good as zoledronic acid at preventing bone lesions, meeting the trial’s primary goal. The median time to a bone event in patients receiving Xgeva was 22.8 months, compared to 24.0 months among those receiving zoledronic acid. Survival rates also were comparable between the two groups.

The most common adverse reactions due to Xgeva were diarrhea, musculoskeletal pain, low blood calcium levels, and shortness of breath.

“Many patients with multiple myeloma have bone lesions at diagnosis, which can result in serious and devastating complications, including broken bones, the need for surgery or radiation to the bone and spinal cord compression,” David M. Reese, MD, senior vice president of Translational Sciences and Oncology at Amgen, said in a press release.

“Until now, treatment options for the prevention of bone complications were limited to bisphosphonates, which unlike Xgeva, are cleared by the kidneys and can be associated with increased renal toxicity. We are pleased with the expanded indication for Xgeva in Europe, underscoring our dedication to advancing care for patients with multiple myeloma,” Reese said.