New drug development in osteoporosis

Tobias De Villiers (ZA)

[De Villiers] Stellenbosch University Cape Town South Africa, Parow

Current therapeutic options in osteoporosis are suboptimal with a need for new drug development. Many promising new compounds have failed registration based on lack of efficacy or poor safety profile. The latest disappointment has been the anti-resorptive compound odanacatib. In spite of good efficacy results, the cardiovascular side effect profile was deemed unacceptable. Romosozumab is an anabolic agent in current development. It is a humanized monoclonal antibody that inhibits sclerostin. In a large placebo-controlled trial, no safety issues were raised but although the primary endpoint of vertebral fracture prevention was met, it failed to prevent non-vertebral fractures. In a smaller study with the comparator alendronate, all the efficiency endpoints were met but a higher rate of cardiovascular events were found in the romosozumab arm. Further evaluation and understanding of these results are required before it can be considered for registration. Abaloparatide is a parathyroid hormone-related protein analog drug that has been approved for the treatment of severe osteoporosis. Like the related drug teriparatide, it is an anabolic agent that can only be used for a 2-year period. When compared to teriparatide, efficacy was better but not significantly so. The side effect profile of both drugs is comparable although abaloparatide was associated with fewer cases of hypercalcemia. As there are no new drugs on the horizon, further improvement in the management of osteoporosis will be based on a better understanding of the sequential use of anti-resorptive and anabolic drugs.