A phase 3 study of romosozumab (Evenity, Amgen/UCB) has met both primary endpoints and a key secondary endpoint. At the primary analysis, treatment with romosozumab for 12 months followed by alendronate significantly reduced the incidence of new vertebral fractures through 24 months, clinical fractures (primary endpoints), and nonvertebral fractures (a key secondary endpoint) in postmenopausal women with osteoporosis at high risk for fracture compared with alendronate alone.
Romosozumab is an investigational bone-forming agent that increases bone formation and reduces bone resorption simultaneously, increases bone mineral density, and reduces the risk of fracture. In the phase 3 ARCH trial, women received subcutaneous injections of romosozumab monthly for 12 months followed by oral alendronate weekly for at least 12 months. At 24 months, women in the romosozumab group experienced a statistically significant 50% reduction in the relative risk of a new vertebral fracture compared with those receiving alendronate alone. Women in the romosozumab group also experienced a significant 27% reduction in the relative risk of clinical fracture (nonvertebral fracture and clinical vertebral fracture) at the primary analysis. In addition, nonvertebral fractures were significantly reduced by 19% in the romosozumab treatment group.
The study, however, also demonstrated an imbalance in cardiovascular serious adverse events between the two treatment groups (2.5% for romosozumab vs. 1.9% for alendronate at 12 months).
Amgen and UCB did not disclose the nature and severity of the heart-related adverse effects, but an industry analyst told Reuters that he believed romosozumab had only a 50/50 chance of coming to market.
Romosozumab is currently under FDA review. Amgen and UCB have stated that they no longer expect the drug to win approval this year because of the higher rate of cardiovascular serious adverse events compared with oral alendronate.