Romosozumab appears to outperform alendronate for fracture prevention in women with osteoporosis, but an increase in cardiovascular adverse events has derailed FDA approval. The drug is a monoclonal antibody that binds to and inhibits sclerostin. In a recent trial, more than 4,000 postmenopausal women with osteoporosis and a fragility fracture were assigned randomly to receive monthly subcutaneous romosozumab or weekly oral alendronate blinded for 12 months, followed by open-label alendronate for both groups for 12 more months. Over 24 months, the rate of new vertebral fractures in the romosozumab group was nearly half that in the alendronate group (6.2% vs. 11.9%; P < 0.001). Clinical fractures also were lower in the romosozumab group (9.7% vs. 13.0%; P < 0.001), with the rate of nonvertebral fractures 19% lower with romosozumab. During the first year, positively adjudicated serious cardiovascular adverse events were observed more often with romosozumab than with alendronate (50 of 2,040 patients vs. 38 of 2,014 patients). The authors stated that in postmenopausal women with osteoporosis who were at high risk for fracture, romosozumab treatment for 12 months followed by alendronate resulted in a significantly lower risk of fracture than alendronate alone. The study was funded by Amgen (N Engl J Med 2017 Sep 11. doi: 10.1056/NEJMoa1708322). In July, the FDA rejected Amgen’s application for approval of the drug based on the increase in cardiovascular events. The company is compiling data from other studies as well as safety data from a new study and expects to refile for approval next year.
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