Odanacatib, a cathepsin K inhibitor for the treatment of osteoporosis and other skeletal disorders associated with excessive bone remodeling.

Odanacatib (MK-0822, MK-822) is an orally administered cathepsin K inhibitor being developed by Merck & Co Inc, under license from Celera Group, for the treatment of osteoporosis and bone metastases. Cathepsin K, a lysosomal cysteine protease that is expressed by osteoclasts during the process of bone resorption, acts as the major collagenase responsible for the degradation of the organic bone matrix during the bone remodeling process. Because excessive bone remodeling is a key element in the pathogenesis of postmenopausal osteoporosis and other skeletal disorders, cathepsin K is a potential target for therapeutic intervention. In a phase II clinical trial, weekly doses of odanacatib increased bone mineral density (BMD) and reduced bone turnover markers in postmenopausal women with low BMD. No tolerability concerns or evidence of skeletal toxicity were reported. Phase III trials, including a trial to evaluate the effects of odanacatib on fracture risk in up to 20,000 women with postmenopausal osteoporosis, were ongoing or recruiting participants at the time of publication. Odanacatib is a promising agent for the management of postmenopausal osteoporosis and other skeletal disorders associated with excessive bone remodeling.