The Food and Drug Administration has approved the monoclonal antibody denosumab (Xgeva), which is indicated for fracture prevention in postmenopausal women at high risk, for the prevention of skeletal-related events in patients with bone metastases from solid tumors.
Denosumab maker Amgen made the announcement. The drug was given a 6-month priority review, indicating that it was considered a major advance in treatment.
“Xgeva has a different mechanism of action than currently approved drugs aimed at reducing bone complications from cancer,” Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA's Center for Drug Evaluation and Research, said in a written statement on the approval for the new indication.
A fully human monoclonal antibody with a unique mechanism of action, denosumab specifically targets the receptor activator of the nuclear factor kappa-B (RANK) ligand, the essential mediator of osteoclast fusion. The drug inhibits osteoclast formation, function, and survival, resulting in reduced bone resorption. The RANK ligand pathway was discovered by Amgen scientists in the mid-1990s, according to the company.
Amgen reported that bone metastases occur in 1.5 million cancer patients worldwide. They are most commonly seen in prostate, lung, and breast cancer. Denosumab was not approved for bone metastases related to multiple myeloma.
“A diagnosis of bone metastases is a major event for patients living with cancer, and the consequences can be devastating,” Amgen chairman and CEO Kevin Sharer wrote in a statement. “We are pleased to offer this new advance to patients and their health care providers.”
The approval of denosumab was based on three phase III head-to-head trials comprising 5,700 patients that compared the drug with zoledronic acid (Zometa).
The drug was superior to zoledronic acid in preventing skeletal-related events (SRE) in breast and prostate cancer. Some of those data were presented in June at the annual meeting of the American Society of Clinical Oncology. Denosumab was noninferior in preventing SREs in multiple myeloma and other solid tumors.
Adverse effects include hypocalcemia, fatigue, hypophosphatemia, and nausea. Osteonecrosis of the jaw can also occur.
Xgeva is delivered every 4 weeks as a 120-mg subcutaneous injection.
Because of the drug's expense, Amgen is launching a new patient assistance program. The Xgeva First Step Coupon Program will provide assistance to eligible patients who need help meeting a deductible, copayment, or coinsurance. The first injection would be covered and subsequent injections would cost a maximum of $25.