Background Odanacatib (ODN) is an orally-active cathepsin K inhibitor being developed for the treatment of postmenopausal osteoporosis.
Objectives This study evaluated the effects of ODN 50mg once weekly on BMD, bone turnover markers and safety in patients previously treated with alendronate (ALN).
Methods This was a randomized, double-blind, placebo-controlled, 24-month study. The primary endpoint was % change from baseline at month 24 of femoral neck (FN) BMD. Postmenopausal women (n=243) ≥60 years of age with low BMD T-score at the total hip, FN or trochanter but no history of hip fracture and who have taken ALN for ≥3years were randomized to receive ODN or placebo. Patients received vitamin D3 and calcium supplementation. BMD was assessed by DXA at baseline, 6, 12 and 24 months. Biochemical markers of bone turnover (sCTx, uNTx, sBSAP and sP1NP) were measured at baseline and 3, 6, 12, 18 and 24 months.
Results In the ODN group, BMD changes from baseline at 24 months were significantly increased from placebo at the femoral neck, trochanter, total hip and lumbar spine (1.7%, 1.8%, 0.8%, and 2.3%, respectively). In the placebo group, BMD at the femoral neck, trochanter and total hip declined significantly from baseline by month 24 (-0.9%, -1.4%, and -1.9% respectively). ODN significantly decreased bone resorption marker, u-NTx/Cr, and significantly increased bone formation markers, s-P1NP and s-BSAP, vs. placebo. The increase observed for the bone resorption marker s-CTx with ODN treatment was unexpected. Adverse events were comparable between the 2 treatments arms. The overall safety profile appeared similar between ODN and placebo.
Conclusions In this study ODN provided incremental BMD gains in osteoporotic women following ALN treatment. Biomarker results suggest that ODN decreases bone resorption while preserving bone formation.
Disclosure of Interest S. Palacios Grant/research support from: Merck Sharp & Dohme Corp., S. Bonnick Grant/research support from: Merck Sharp & Dohme Corp., T. De Villiers Speakers bureau: Merck Sharp & Dohme Corp., R. Chapurlat Grant/research support from: Merck Sharp & Dohme Corp., Consultant for: Merck Sharp & Dohme Corp., A. Odio: None Declared, B. Scott Employee of: Merck Sharp & Dohme Corp., C. Le Bailly De Tilleghem Employee of: Merck Sharp & Dohme Corp., C. DaSilva Employee of: Merck Sharp & Dohme Corp., A. Leung Employee of: Merck Sharp & Dohme Corp., D. Gurner Employee of: Merck Sharp & Dohme Corp.
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