FDA accepts supplemental application for Xgeva to treat patients with multiple myeloma

The FDA accepted a supplemental biologics application that seeks to expand the approval of denosumab to include patients with multiple myeloma, according to the drug’s manufacturer.

Denosumab (Xgeva, Amgen) is the first fully human monoclonal antibody that binds to and neutralizes RANK ligand, a protein that is vital for the formation, function and survival of osteoclasts.

The agent is approved to prevent fractures and other skeletal-related events among patients with bone metastases from solid tumors.

The supplemental application included data from the pivotal phase 3 '482 study, which compared the efficacy and safety of denosumab with zoledronic acid for the prevention of skeletal-related events in adults with newly diagnosed multiple myeloma.

Researchers randomly assigned 1,718 patients to 120 mg subcutaneous denosumab plus IV placebo every 4 weeks or 4 mg IV zoledronic acid and subcutaneous placebo every 4 weeks.

Denosumab appeared noninferior to zoledronic acid for delaying the time to first on-study skeletal-related event.

Patients assigned denosumab achieved superior PFS (HR = 0.82; 95% CI, 0.68-0.99, with a 10.7-month difference between treatment groups.

The study did not meet its secondary endpoints, which included superiority with regard to delayed time to first on-study skeletal-related event, and delayed time to first and subsequent skeletal-related event.

The most common adverse events included diarrhea and nausea.

“Multiple myeloma patients with fractures and other bone complications have a very poor prognosis,” Sean E. Harper, MD, executive vice president of research and development at Amgen, said in a company-issued press release. “Bisphosphonates are the only approved class of agents for the prevention of skeletal-related events in this patient population.

“However, these agents have several limitations, including kidney toxicity and acute phase reactions,” Harper added. “Based on the data we have submitted to the FDA, we look forward to potentially making Xgeva available as a novel option for patients with multiple myeloma.”

The FDA set an action date of Feb. 3, 2018.