The U.S. Food and Drug Administration (FDA) has accepted a supplemental biologics license application (sBLA) seeking to expand the currently approved indication of Xgeva (denosumab) to include patients with multiple myeloma, the biotechnology company Amgen announced.
Xgeva is indicated for the prevention of fractures, spinal cord compression, or the need for radiation or surgery in bones for patients with bone metastases from solid tumors. However, Xgeva is not used to prevent these bone problems in patients with myeloma, which is what this sBLA seeks.
Myeloma develops in plasma cells located in the bone marrow and is characterized by osteolytic bone lesions (due to the loss of calcium) and renal impairment. The majority of myeloma patients develop osteolytic lesions and current treatment options are limited to bisphosphonates, including Zometa (zoledronic acid), which are cleared by the kidneys and are associated with renal toxicity.
Xgeva is the first fully human monoclonal antibody that binds to and neutralizes a protein (RANK ligand) essential for the formation, function and survival of osteoclasts (a type of cell that breaks down bone), which avoids bone destruction.
The sBLA was submitted in April, supported by safety and effectiveness data from the pivotal Phase 3 ‘482 Study (NCT01345019), which the company said is the largest international multiple myeloma trial ever conducted. In that trial, Xgeva was successfully shown to be non-inferior to Zometa in delaying time to a skeletal-related event in patients with myeloma.
In the Phase 3 trial, Xgeva did not achieve secondary endpoint measurements with a favorable profile. However, the time to disease progression or death among patients receiving Xgeva was 10.7 months longer than in those receiving Zometa, which represents an 18 percent reduction in the risk of progression, favoring the use of Xgeva in these patients.
“Multiple myeloma patients with fractures and other bone complications have a very poor prognosis. 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,” Sean E. Harper, MD, said in a press release. “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,” said Harper, who is executive vice president of research and development at Amgen.
The Phase 3 study also supported the submission of a marketing authorization application to the European Medicines Agency (EMA). The FDA has set a prescription drug user act (PDUFA) action date of Feb. 3, 2018, to rule on the sBLA.