Romosozumab binds to and inhibits sclerostin, a negative regulator of bone formation. In addition to stimulating bone formation, it also inhibits bone resorption.
According to a commentary, it is not uncommon to encounter patients in clinical practice, who despite adequate adherence to medication apparently do not respond to oral bisphosphonates, with persistently low BMD or incident fracture during treatment. It notes some of these patients might respond to intravenous bisphosphonates, but in others switching to a drug that stimulates bone formation seems a reasonable approach. It acknowledges that although the effects on fracture risk have not been established, the results of this study do suggest that the greatest benefits for hip BMD and estimated strength are obtained with a drug such as romosozumab that stimulates bone formation and inhibits bone resorption. It points out that use of sequential therapy in osteoporosis is the focus of much attention, and this study shows the potential for the use of drugs with different mechanisms of action as a strategy to improve outcomes in the management of osteoporosis. It adds that since the duration of therapy with bone-forming agents is limited and bone loss follows treatment withdrawal, the subsequent use of interventions to maintain treatment benefits is an important area for future research.
In July 2017, the FDA did not approve romosozumab in US. It requested new safety and efficacy data from the phase III active-comparator ARCH study to be integrated into the drug’s submission, which was based on the pivotal FRAME study. UCB is scheduled to submit a marketing application in Europe in second half of 2017.