Effects of Odanacatib on BMD and Overall Safety in the Treatment of Osteoporosis in Postmenopausal Women Previously Treated with Alendronate
Category: Osteoporosis - Treatment (Clinical)
Oral Presentations, Presentation Number: 1027
Session: Concurrent Oral Session 05: John H. Carsten's Memorial Session for Osteoporosis Treatment
Saturday, October 13, 2012 10:00 AM - 10:15 AM, Minneapolis Convention Center, Auditorium-Main
* Tobias De Villiers, Mediclinic Panorama, South Africa, Sydney Bonnick, Clinical Research Center of North Texas, USA, Alberto Odio, Alta California Medical Group, USA, Santiago Palacios, Instituto Palacios, Salud y Medicina de la Mujer C/Antonio Acuña, Spain, Roland Chapurlat, E. Herriot Hospital, FRANCE, Boyd Scott, Merck & Co., Inc., USA, Celine Le Bailly De Tilleghem, Merck Sharp & Dohme Corp., USA, Carolyn DaSilva, Merck & Co., Inc., USA, Albert Leung, Merck & Co. Inc., USA, USA, Deborah Gurner, MSD, USA
Odanacatib (ODN) is a potent, orally-active cathepsin K inhibitor being developed for the treatment of postmenopausal osteoporosis. This study evaluated the effects of ODN 50mg once weekly (OW) on BMD and biochemical markers of bone turnover in patients previously treated with alendronate (ALN) (dosed daily or weekly) for ≥3years as well as the safety and tolerability of ODN. This study was not designed nor had the power to evaluate the effect of ODN on fractures.
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. 243 postmenopausal women ≥60 years of age with low BMD T-score (T-score range ≤–2.5 but >-3.5) at the total hip, FN or trochanter but no history of hip fracture and who had been treated with ALN for ≥3years were randomized in a 1:1 ratio to receive ODN 50mg OW or placebo OW for 24 months. All patients received vitamin D3 5600 IU/wk and calcium supplementation (to 1200 mg/day). BMD was assessed by DXA at baseline, 6, 12 and 24 months. Biochemical markers of bone turnover (s-CTx, u-NTx, s-BSAP and s-P1NP) were measured at baseline and 3, 6, 12, 18 and 24 months.
In the placebo group, BMD at the FN and trochanter were not significantly different from baseline levels for the first 12 months, but declined significantly from baseline by Month 24 (-0.94% and -1.35%, respectively). Total hip BMD declined in a linear manner from baseline to month 24 (-1.87% at 24 months). At the lumbar spine (LS), BMD was not significantly different from baseline for the entire 24 months of the study. In the ODN group, BMD changes from baseline at 24 months were significant vs placebo at all 3 hip sites and the LS. The changes from baseline were 1.73%, 1.83%, 0.83% and 2.28%, respectively, for the FN, trochanter, total hip and LS. ODN 50mg OW significantly decreased the biomarker of bone resorption, u-NTx/Cr, and significantly increased biomarkers of bone formation, s-P1NP and s-BSAP, compared to placebo. The increase observed for the bone resorption marker s-CTx with ODN treatment was unexpected. AEs were comparable between the 2 treatment arms. The overall safety profile appeared similar between ODN 50mg OW and placebo.
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.
Disclosures: C. Le Bailly De Tilleghem, Merck Sharp & Dohme Corp.: Employment (full or part-time). S. Bonnick, Merck Sharp & Dohme Corp.: Research Grants. C. DASILVA, Merck Sharp & Dohme Corp.: Employment (full or part-time). R. Chapurlat, Merck Sharp & Dohme Corp.: Research Grants. T. De Villiers, Merck Sharp & Dohme Corp.: Speaker's Bureau. B. Scott, Merck Sharp & Dohme Corp.: Employment (full or part-time). T. De Villiers, Merck Sharp & Dohme Corp.: Other. R. Chapurlat, Merck Sharp & Dohme Corp.: Consulting fees or other remuneration (payment). A. Leung, Merck Sharp & Dohme Corp.: Employment (full or part-time). S. Palacios, Merck Sharp & Dohme Corp.: Research Grants. D. Gurner, Merck Sharp & Dohme Corp.: Employment (full or part-time).
* Presenting Authors(s): Tobias De Villiers, Mediclinic Panorama, South Africa