OP34 - ODANACATIB IN THE TREATMENT OF POSTMENOPAUSAL WOMEN WITH LOW BONE MINERAL DENSITY: 3-YEAR CONTINUED THERAPY AND RESOLUTION OF EFFECT
D. Hosking1, J. A. Eisman2, H. Bone3, M. McClung4, I. Reid5, R. Rizzoli6, H. Resch7, N. Verbruggen8, C. Hustad9, A. Santora10, A. Lombardi10
1Nottingham City Hospital, Nottingham, UK, United Kingdom, 2Garvan Institute of Medical Research, St Vincent’s Hospital, Sydney, Australia, 3Michigan Bone and Mineral Center, Detroit, United States, 4Oregon Osteoporosis Center, Portland, United States, 5University of Auckland, Auckland, New Zealand, 6University Hospital Cantonal, Geneva, Switzerland, 7St. Vincent Hospital, Vienna, Austria, 8Merck Research Laboratories, Brussels, Belgium, 9MERCK & CO., INC., North Wales, United States, 10Merck Research Laboratories, Rahway, United States
Abstract: Background: Odanacatib (ODN), a selective cathepsin K inhibitor, progressively increased bone mineral density (BMD) and decreased bone resorption markers during 2 years of treatment in a dose-ranging study of postmenopausal women with low BMD. A 1-year extension study assessed the efficacy and safety of ODN and the effects of discontinuing therapy.
Methods: In the base study, postmenopausal women with BMD T-scores between -2.0 and -3.5 at the lumbar spine, femoral neck, trochanter or total hip (n=399) received placebo or ODN at 3, 10, 25 or 50 mg weekly. After 2 years, patients (n=189) remaining blinded were re-randomized to ODN 50 mg weekly or placebo for an additional year, and 169 completed 3 years. Endpoints included BMD at the lumbar spine (primary), total hip and hip subregions, and 1/3 radius; levels of bone turnover markers; and assessments of safety and tolerability.
Results: Continued treatment with 50 mg ODN for 3 years produced significant increases from baseline and during the third year in spine (8% and 2%), total hip (6% and 2%), femoral neck (5% and 2%), and trochanter (7% and 3%) BMD and maintained BMD at the 1/3 radius. Urine NTx remained suppressed at Month 36 (-50%), but BSAP rose to slightly above baseline (18%) after the initial decrease. Treatment discontinuation resulted in bone loss at all sites, with higher rates in the initial 6 months and less loss between Months 30 and 36. At the end of Year 3, mean BMD among patients who took 50 mg ODN for 2 years and placebo in the third year was still above baseline at the femoral neck, was near baseline at the spine, and did not differ from placebo for total hip, trochanter, and 1/3 radius. Following ODN discontinuation, biochemical markers of bone remodeling increased rapidly above baseline values. This rebound in bone turnover occurred promptly after treatment discontinuation and largely resolved with time. For example, mean urine NTx increased to 50% above baseline by Month 30, but was only approximately 28% above baseline by Month 36. No differences in the overall incidence of adverse events were observed between the pooled placebo and ODN treatment groups.
Conclusion: Three 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 were relatively less affected. BMD increases and resorption biomarker suppression with ODN were substantially reversed following discontinuation of treatment.
Disclosure of Interest: D. Hosking Grant / Research support from Merck Research Laboratories, J. Eisman Grant / Research support from Merck Research Laboratories, H. Bone Grant / Research support from Merck Research Laboratories, M. McClung Grant / Research support from Merck Research Laboratories, I. Reid Grant / Research support from Merck Research Laboratories, R. Rizzoli Grant / Research support from Merck Research Laboratories, H. Resch Speakers Bureau with Merck Research Laboratories, N. Verbruggen Employee of Merck Research Laboratories, C. Hustad Employee of Merck Research Laboratories, A. Santora Employee of Merck Research Laboratories, A. Lombardi Employee of Merck Research Laboratories
Keywords: bone mineral density, Postmenopausal women
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