Safety and efficacy of the cathepsin K inhibitor ONO‐5334 in postmenopausal osteoporosis: The OCEAN study

Osteoporosis occurs when there is an imbalance between resorption and formation of bone, with resorption predominating. Inhibitors of cathepsin K may rebalance this condition. This is the first efficacy study of a new cathepsin K inhibitor, ONO‐5334. The objective of the study was to investigate the efficacy and safety of ONO‐5334 in postmenopausal osteoporosis. This was a 12‐month, randomized, double‐blind, placebo‐ and active‐controlled parallel‐group study conducted in 13 centers in 6 European countries. Subjects included 285 postmenopausal women aged 55 to 75 years with osteoporosis. Subjects were randomized into one of five treatment arms: placebo; 50 mg twice daily, 100 mg once daily, or 300 mg once daily of ONO‐5334; or alendronate 70 mg once weekly. Lumbar spine, total hip, and femoral neck BMD values were obtained along with biochemical markers of bone turnover and standard safety assessments. All ONO‐5334 doses and alendronate showed a significant increase in BMD for lumbar spine, total hip (except 100 mg once daily), and femoral neck BMD. There was little or no suppression of ONO‐5334 on bone‐formation markers compared with alendronate, although the suppressive effects on bone‐resorption markers were similar. There were no clinically relevant safety concerns. With a significant increase in BMD, ONO‐5334 also demonstrated a new mode of action as a potential agent for treating osteoporosis. Further clinical studies are warranted to investigate long‐term efficacy as well as safety of ONO‐5334. © 2011 American Society for Bone and Mineral Research.