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    ASBMR 2010 Annual Meeting

    Effect of Odanacatib on Bone Density and Bone Turnover Markers in Postmenopausal Women with Low Bone Mineral Density: Year 4 Results

    Category: Osteoporosis - Treatment (Clinical)

    Oral Presentations, Presentation Number: 1247
    Session: Concurrent Oral Session 42: Osteoporosis Treatment: Pharmacologic and Non-Pharmacologic
    Monday, October 18, 2010 4:30 PM - 4:45 PM, Metro Toronto Convention Centre, South Building, South Building: Hall G

    * Neil Binkley, University of Wisconsin, Madison, USA, Henry Bone, Michigan Bone and Mineral Clinic, USA, John Eisman, Garvan Institute of Medical Research, AUSTRALIA, David Hosking, Nottingham City Hospital, UNITED KINGDOM, Bente Langdahl, Aarhus University Hospital, DNK, Ian Reid, University of Auckland, NEW ZEALAND, Heinrich Resch, Medical University Vienna, AUSTRIA, Jose Rodriguez Portales, Pontificia Universidad Católica de Chile, Chile, Romana Petrovic, Merck Sharpe & Dohme, Belgium, Carolyn Hustad, Merck, USA, Carolyn DaSilva, Merck, USA, Arthur Santora, Merck & Co. Inc., USA, Antonio Lombardi, Merck & Co., Inc., USA

    The selective cathepsin K inhibitor odanacatib (ODN) reduced bone resorption markers and progressively increased bone mineral density (BMD) during 3 years of treatment in a Phase 2b study. This study was extended for 2 additional years to further assess ODN efficacy and long-term safety.
    In the 2-year base study, postmenopausal women with BMD T-scores between -2.0 and -3.5 at the lumbar spine, femoral neck, trochanter or total hip received placebo or ODN at 3, 10, 25 or 50 mg weekly. In Year 3, participants were re-randomized to ODN 50 mg weekly or placebo. In Years 4/5, women who received placebo or 3 mg ODN in Years 1/2 and placebo in Year 3 were switched to 50 mg ODN for Years 4/5; all others continued with their Year 3 regimen. 141 women entered the extension, and 133 completed 4 years. Endpoints were BMD at the lumbar spine (primary), total hip and hip subregions, and 1/3 radius; levels of biochemical bone turnover markers; and assessments of safety.
    Overall, 100 women received 50 mg ODN during Year 4 and 41 received placebo. Continuous treatment with 50 mg ODN for 4 years induced significant BMD increases from baseline at the spine (10.7%), total hip (8.3%), femoral neck (8.9%), and trochanter (10.3%) and maintained BMD (-0.1%) at the 1/3 radius; BMD changes from Year 3 were 2.8% (spine), 2.5% (total hip), 3.9% (femoral neck), and 2.9% (trochanter). Serum CTx remained low at Year 4 (-41%), whereas BSAP was relatively unchanged (-2%) from baseline. Women who received active treatment for 2 years and switched to placebo for 2 years experienced bone loss, with BMD near baseline for most sites and decreased by 4.5% at the 1/3 radius at the end of Year 4. Levels of bone turnover markers in women who discontinued active treatment after 2 years rose in the first month off-treatment, but all levels returned to baseline by the end of Year 4. ODN was generally well tolerated.
    In summary, 4 years of ODN treatment increased lumbar spine and hip BMD and was generally well-tolerated in postmenopausal women with low bone mass. Bone formation markers remained relatively unaffected. Discontinuation of ODN after 2 years of treatment was promptly followed by resolution of effects on bone turnover and density such that BMD and bone biomarker levels at Year 4 were at or near baseline.

    Disclosures: D. Hosking, Merck: Research Grants. R. Petrovic, Merck Sharpe & Dohme: Employment (full or part-time). J. Rodriguez Portales, Merck: Research Grants. C. Hustad, Merck: Employment (full or part-time). H. Bone, Merck: Research Grants. I. Reid, Merck: Research Grants. B. Langdahl, Merck: Research Grants. C. Hustad, Merck: Stock options or bond holdings in a for-profit corporation or self-directed pension plan. A. Lombardi, Merck: Stock options or bond holdings in a for-profit corporation or self-directed pension plan. H. Resch, Merck: Research Grants. A. Lombardi, Merck: Employment (full or part-time). R. Petrovic, Merck Sharpe & Dohme: Stock options or bond holdings in a for-profit corporation or self-directed pension plan. C. DaSilva, Merck: Stock options or bond holdings in a for-profit corporation or self-directed pension plan. N. Binkley, Merck: Research Grants. A. Santora, Merck: Employment (full or part-time). C. DaSilva, Merck: Employment (full or part-time). A. Santora, Merck: Stock options or bond holdings in a for-profit corporation or self-directed pension plan. J. Eisman, Merck: Research Grants.

    * Presenting Authors(s): Neil Binkley, University of Wisconsin, Madison, USA

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