Continuous treatment with odanacatib for up to 8 years in postmenopausal women with low bone mineral density: a phase 2 study

Summary The efficacy and safety of weekly oral odanacatib (ODN) 50 mg for up to 8 years were assessed in postmenopausal women with low bone mineral density (BMD). Treatment with ODN for up to 8 years resulted in continued or maintained increases in BMD at multiple sites and was well tolerated. Introduction ODN is a selective inhibitor of cathepsin K. In a 2-year phase 2b study (3/10/25/50 mg ODN once weekly [QW] or placebo) and extensions (50 mg ODN QW or placebo), ODN treatment for 5 years progressively increased BMD and decreased bone resorption markers in postmenopausal women with low BMD ( ClinicalTrials.gov NCT00112437). Methods In this prespecified interim analysis at year 8 of an additional 5-year extension (years 6 to 10), patients ( n = 117) received open-label ODN 50 mg QW plus weekly vitamin D 3 (5600 IU) and calcium supplementation as needed. Primary end points were lumbar spine BMD and safety. Patients were grouped by ODN exposure duration. Results Mean (95 % confidence interval [CI]) lumbar spine BMD changes from baseline were 4.6 % (2.4, 6.7; 3-year continuous ODN exposure), 12.9 % (8.1, 17.7; 5 years), 12.8 % (10.0, 15.7; 6 years), and 14.8 % (11.0, 18.6; 8 years). Similar patterns of results were observed for BMD of trochanter, femoral neck, and total hip versus baseline. Geometric mean changes from baseline to year 8 for bone resorption markers were approximately −50 % (uNTx/Cr) and −45 % (sCTx), respectively (all groups); bone formation markers remained near baseline levels. No osteonecrosis of the jaw, delayed fracture union, or morphea-like skin reactions were reported. Conclusions Treatment with ODN for up to 8 years resulted in gains in BMD at multiple sites. Bone resorption markers remained reduced, with no significant change observed in bone formation markers. Treatment with ODN for up to 8 years was well tolerated.