Pharmacological characteristics and clinical study results of romosozumab (Evenity®; genetical recombination), a drug with novel mechanism of action to treat osteoporosis at high risk of fracture

Abstract

Romosozumab (EVENITY®) is a humanized monoclonal antibody designed to target sclerostin. Sclerostin is a glycoprotein that is secreted by osteocytes and that inhibits Wnt signaling in osteoblast lineage cells, leading to decreased bone formation by osteoblasts and increased bone resorption by osteoclasts. Romosozumab, by binding and inhibiting sclerostin, increases bone formation and decreases bone resorption. Romosozumab is known to mainly enable increase in modeling-based bone formation. In studies using ovariectomized (OVX) models of rats and cynomolgus monkeys, those administered romosozumab showed dose-dependently increased bone mass and strength. In addition, the bone-forming effect of romosozumab decreased after continued administration. In rats, romosozumab caused almost no focal osteoblast hyperplasia or benign or malignant bone tumors, presumably owing to the time-dependent decrease in the bone-forming effect. Clinical studies demonstrated inhibition of new vertebral fractures at 12 months of treatment, and increased bone mineral density at 6 months of treatment. With a dual effect on bone, increasing bone formation and decreasing bone resorption, romosozumab is expected to become a new treatment option, and was approved in January 2019 for the indication of “patients with osteoporosis at high risk for fracture”.