FDA Extends Xgeva Approval to Include Myeloma Patients with Bone Lesions

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by Alice Melão |

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The U.S. Food and Drug Administration (FDA) has agreed to extend Xgeva‘s (denosumab) approval to include patients with multiple myeloma who have bone lesions.

The drug, meant to prevent fractures, spinal cord compression, or the need for radiation or surgery in bones, was already indicated for patients with bone metastases from solid tumors.

Amgen‘s supplemental Biologics License Application (BLA) for the myeloma approval was supported by clinical data from a pivotal Phase 3 study (NCT01345019).

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.

Until this FDA approval, treatment options were limited to bisphosphonates, including Zometa (zoledronic acid). But these are cleared by the kidneys and are associated with renal toxicity.

“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,” Noopur Raje, MD, director of the Center for Multiple Myeloma at Massachusetts General Hospital Cancer Center, said in a press release.

“Denosumab [Xgeva], 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,” Raje said.

Amgen’s Xgeva is an antibody that inhibits the activity of the RANK ligand (RANKL), a protein that is essential for the formation, function, and survival of osteoclasts. By blocking osteoclast-mediated bone destruction, Xgeva prevents bone lesions with fewer treatment-related adverse events.

The international Phase 3 study included 1,718 patients newly diagnosed with multiple myeloma and bone disease. Participants were randomized to receive either subcutaneous Xgeva plus an intravenous placebo, or intravenous Zometa plus subcutaneous placebo, every four weeks.

The trial met its primary endpoint, demonstrating that Xgeva was at least as good as Zometa at preventing skeletal lesions. Survival was also comparable between the two drugs.

However, researchers found that patients taking Xgeva lived for a median of 46.1 months, while the time of progression-free survival was only 35.4 months in the Zometa arm. This suggested that Xgeva delayed disease progression by 10.7 months.

The most common adverse events related to Xgeva treatment were diarrhea, nausea, anemia, back pain, low levels of blood platelets, swelling of the lower limbs, low levels of calcium, upper respiratory tract infection, rash, and headache.

“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 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,” he added.

Xgeva is currently the No. 1 prescribed bone-targeting agent in the U.S. for the prevention of skeletal-related events in patients with bone metastases from solid tumors. Regulatory applications requesting the extension of the Xgeva indication to include patients with multiple myeloma are underway and have been submitted to health authorities in other countries.