Endocrine Abstracts

The treatment of osteoporosis consists of either antiresorptive or anabolic approaches. While there are a number of antiresorptive options available (i.e. bisphosphonates, SERMs and denosumab), teriparatide (PTH 1-34) is currently the only bone anabolic agent approved in the EU. The PTH-related protein (PTHrP) analogue abaloparatide and the sclerostin antibody romosozumab are two anabolic agents that are in the approval process for the treatment of postmenopausal osteoporosis. In the phase 3 ACTIVE trial abaloparatide was compared to placebo and teriparatide for 18 months in postmenopausal women who had already experienced an osteoporotic fracture. Abaloparatide successfully reduced the rate of new vertebral fractures by 86% compared to placebo. Furthermore, abaloparatide achieved greater BMD increases at all measured sites compared to placebo and teriparatide. Based on these results, abaloparatide was FDA approved in April 2017. Romosozumab is a monoclonal antibody that targets the Wnt inhibitor sclerostin. Two phase 3 trials of romosozumab for the treatment of postmenopausal osteoporosis have been completed. The FRAME trial was placebo controlled. After 12 months of romosozumab or placebo, patients were switched to an additional 12 months of denosumab in both groups. The ARCH trial included women that had already experienced a vertebral fracture and compared 12 months of romosozumab to alendronate. After 12 months all patients were switched to open label alendronate. Both trials successfully reached their primary endpoint by reducing vertebral fractures by 75% (FRAME trial) and 48% (ARCH trial) at 24 months, respectively. In the ARCH trial a safety signal for cardiovascular events, not previously seen in other romosozumab trials, was detected with a numerical imbalance between romosozumab (2.5%) and alendronate (1.9%). These results warranted further analyses and have prolonged the approval process for romosozumab.