OP0248 Inhibition of Sclerostin with Romosozumab in Postmenopausal Women with Low Bone Mineral Density: Phase 2 Trial Results
Authors: M. R. McClung, A. Grauer, S. Boonen, J. P. Brown, A. Diez-Perez, B. L. Langdahl, J.-Y. Reginster, J. R. Zanchetta, L. Katz, J. Maddox, Y.-C. Yang, C. Libanati, H. G. Bone
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In preclinical studies, administration of antibodies that neutralize sclerostin results in increased bone mass and strength. <h3>Objectives</h3> We report the primary and key secondary endpoints of a phase 2 trial evaluating the efficacy and safety of the human sclerostin antibody AMG 785/CDP7851 (romosozumab) in postmenopausal women with low bone mineral density (BMD). <h3>Methods</h3> This international, randomized, placebo-controlled, phase 2 study enrolled postmenopausal women aged 55 to 85 years with a lumbar spine, total hip, or femoral neck T-score ≤–2.0 and ≥–3.5. During the first 12 months, women were randomized to one of 5 regimens of subcutaneous romosozumab (70 mg QM, 140 mg QM, 210 mg QM, 140 mg Q3M, 210 mg Q3M) or placebo, and one of 2 open-label active comparators: 70 mg weekly oral alendronate (ALN) or 20 μg daily subcutaneous teriparatide (TPTD). The primary endpoint was percentage change from baseline in lumbar spine BMD at month 12 (romosozumab compared with placebo). <h3>Results</h3> The women enrolled in the study (N=419) had a mean age of 67 years, and mean lumbar spine, total hip, and femoral neck T-scores of –2.3, –1.5, and –1.9, respectively. All romosozumab doses significantly increased BMD compared with placebo at each of the 3 sites at month 12 (<i>p</i>&lt;0.005). The largest gains were observed with romosozumab 210 mg QM which resulted in rapid increases from baseline in BMD reaching 11.3% at the lumbar spine and 4.1% at the total hip. These increases were significantly greater than those achieved with ALN and TPTD (p&lt;0.0001). All doses of romosozumab increased serum PINP and reduced serum CTX from baseline by week 1. Bone turnover marker changes with ALN and TPTD showed expected profiles (ie, decreases in both markers with ALN, and increases in both markers with TPTD). In general, adverse events were balanced between the total romosozumab and placebo groups with the exception of generally mild injection site reactions (12% romosozumab; 4% placebo). <h3>Conclusions</h3> Romosozumab led to rapid and marked increases in BMD which were superior to those observed with ALN and TPTD and were due to romosozumab's simultaneous stimulation of bone formation and decrease in bone resorption. Romosozumab was generally well tolerated. These data support the continued clinical investigation of romosozumab as a potential therapeutic agent for the treatment of postmenopausal women with osteoporosis. <h3>Disclosure of Interest</h3> M. McClung Grant/research support from: Amgen Inc., Merck, Consultant for: Amgen Inc., Lilly, Merck, Novartis, Warner-Chilcott, Speakers bureau: Amgen Inc., Lilly, Merck, Novartis, Warner-Chilcott, A. Grauer Shareholder of: Amgen Inc., Employee of: Amgen Inc., S. Boonen Grant/research support from: Amgen Inc., Novartis, Consultant for: Amgen Inc., Novartis, Speakers bureau: Amgen Inc., Novartis, J. Brown Grant/research support from: Amgen Inc., Eli Lilly, Merck, Novartis, Pfizer, Servier, Roche, Takeda, Warner Chilcott, Consultant for: Amgen Inc., Eli Lilly, Merck, Speakers bureau: Amgen Inc., Eli Lilly, Merck, A. Diez-Perez Grant/research support from: Amgen Inc., Consultant for: Lilly, Novartis, Amgen Inc., Pfizer, ViiV, Speakers bureau: Lilly, Novartis, Amgen Inc., Pfizer, ViiV, B. Langdahl Grant/research support from: Merck, Lilly, Novartis, Amgen Inc., Consultant for: Merck, Lilly, Amgen Inc., Speakers bureau: Merck, Lilly, Amgen Inc., J.-Y. Reginster Grant/research support from: Bristol Myers Squibb, Merck Sharp and Dohme, Lilly, Rottapharm, Teva, Novartis, GlaxoSmithKline, Roche, Amgen Inc., Servier, Consultant for: Servier, Novartis, Negma, Lilly, Wyeth, Amgen Inc., GlaxoSmithKline, Roche, Merckle, Nycomed, NPS, Theramex, UCB, Paid instructor for: Merck Sharp and Dohme, Lilly, Rottapharm, IBSA, Genevrier, Servier, Novartis, GlaxoSmithKline, Roche, Teijin, Teva, Ebewee Pharma, Zodiac, Analis, Nycomed, Theramex, Novo-Nordisk, Nolver, J. Zanchetta Consultant for: Amgen Inc., Eli Lilly, Merck, GSK, Pfizer, Speakers bureau: Amgen Inc., Eli Lilly, Merck, GSK, Pfizer, L. Katz Shareholder of: Amgen Inc., Employee of: Amgen Inc., J. Maddox Shareholder of: Amgen Inc., Employee of: Amgen Inc., Y.-C. Yang Shareholder of: Amgen Inc., Employee of: Amgen Inc., C. Libanati Shareholder of: Amgen Inc., Employee of: Amgen Inc., H. Bone Grant/research support from: Amgen Inc., Merck, Novartis, Tarsa, Consultant for: Amgen Inc., Merck, Tarsa, Speakers bureau: Amgen Inc., Merck, Tarsa