Mona Chitre1, David Shechter, Andreas Grauer. 1. Clinical Services, Strategy and Policy, Excellus BlueCross BlueShield, Rochester, NY 14647, USA. mona.chitre@flrx.com
Abstract
PURPOSE: The pharmacologic properties, clinical efficacy, and safety profile of the injectable agent denosumab for the treatment of postmenopausal women with osteoporosis are reviewed. SUMMARY: Denosumab, a human monoclonal antibody that targets a key protein mediator of bone resorption, was approved by the Food and Drug Administration in June 2010 for the treatment of postmenopausal women with osteoporosis who are at high risk for fracture, including "patients who have failed or are intolerant to other available osteoporosis therapy." Available in a 60-mg prefilled syringe, denosumab should be administered subcutaneously by a health care professional at six-month intervals. In Phase III clinical efficacy trials involving nearly 10,000 postmenopausal women, the use of denosumab was associated with a number of significant benefits: reduced bone resorption, increased bone mass, and reduced rates of vertebral, nonvertebral, and hip fractures. Results of two comparison studies indicated that denosumab therapy increased bone mineral density (BMD) at various skeletal sites to a significantly greater extent than alendronate therapy. In the largest clinical trial of the drug to date, adverse effects occurring significantly more often with denosumab versus placebo included eczema-related effects and cellulitis; long-term safety evaluations are ongoing. CONCLUSION: Denosumab has been shown to decrease bone resorption; increase BMD at all skeletal sites measured; and significantly reduce rates of vertebral, nonvertebral, and hip fractures in postmenopausal women with osteoporosis. Denosumab appears to have a favorable risk:benefit profile and provides a new treatment option for many patients in this population.
PURPOSE: The pharmacologic properties, clinical efficacy, and safety profile of the injectable agent denosumab for the treatment of postmenopausal women with osteoporosis are reviewed. SUMMARY:Denosumab, a human monoclonal antibody that targets a key protein mediator of bone resorption, was approved by the Food and Drug Administration in June 2010 for the treatment of postmenopausal women with osteoporosis who are at high risk for fracture, including "patients who have failed or are intolerant to other available osteoporosis therapy." Available in a 60-mg prefilled syringe, denosumab should be administered subcutaneously by a health care professional at six-month intervals. In Phase III clinical efficacy trials involving nearly 10,000 postmenopausal women, the use of denosumab was associated with a number of significant benefits: reduced bone resorption, increased bone mass, and reduced rates of vertebral, nonvertebral, and hip fractures. Results of two comparison studies indicated that denosumab therapy increased bone mineral density (BMD) at various skeletal sites to a significantly greater extent than alendronate therapy. In the largest clinical trial of the drug to date, adverse effects occurring significantly more often with denosumab versus placebo included eczema-related effects and cellulitis; long-term safety evaluations are ongoing. CONCLUSION:Denosumab has been shown to decrease bone resorption; increase BMD at all skeletal sites measured; and significantly reduce rates of vertebral, nonvertebral, and hip fractures in postmenopausal women with osteoporosis. Denosumab appears to have a favorable risk:benefit profile and provides a new treatment option for many patients in this population.