MD Conference Express - ENDO 2015 - (Page 21)

Table 2. Studies of Antisclerostin Monoclonal Antibodies in Postmenopausal Women Study Patients/Methods Results Romosozumab Phase 1 single dose [Padhi D et al. J Bone Miner Res. 2011] 72 PM women randomized to single doses of romosozumab or placebo Dose-related increases in P1NP, BAP, osteocalcin Dose-related decrease in CTX BMD increased up to 5.3% (LS) and 2.8% (TH) on day 85 with 10 mg/kg (P < .01) Generally well tolerated Phase 1 multiple dose [Padhi D et al. J Clin Pharmacol. 2014] PM women with low bone mass randomized to ascending doses of romosozumab or placebo P1NP increased by 66% to 147% CTX decreased by 15% to 50% LS BMD increased by 4% to 7% No significant safety findings Phase 2 efficacy and tolerability [McClung MR et al. N Engl J Med. 2014] 419 PM women with low BMD randomized to 1 of 5 SC romosozumab dosing regimens; oral ALN, 70 mg weekly; SC TPT, 20 µg daily; or placebo injections LS BMD increase: romosozumab 210 mg QM (11.3%; P < .05 vs placebo; P < .02 vs ALN and TPT), TPT (7.1%), ALN (4.1%) TH BMD increase: romosozumab 210 mg QM (4.1%; P < .05 vs placebo; P < .02 vs ALN and TPT), ALN (1.9%), TPT (1.3%) FN BMD increase: romosozumab 210 mg QM (3.7%; P < .05 vs placebo; P < .02 vs ALN and TPT), ALN (1.2%), TPT (1.1%) P1NP: rapid transient increase with romosozumab 210 mg QM, returning to baseline by 6 to 12 mo CTX: rapid transient decrease with romosozumab 210 mg QM, returning to baseline by 3 mo Adverse events similar between romosozumab and placebo Blosozumab Phase 1 single and multiple dose studies [McColm J et al. J Bone Miner Res. 2014] Phase 2 vs placebo [Recker RR et al. J Bone Miner Res. 2015] PM women with low BMD randomized to escalating blosozumab doses: single IV doses up to 750 mg; single SC dose of 150 mg; multiple IV doses to 750 mg; multiple SC doses to 270 mg Q2W; or placebo LS BMD increase: up to 3.41% with single dose and up to 7.71% with multiple dose at day 85 PM women with low BMD (n = 120) randomized to blosozumab-180 mg Q4W, 180 mg Q2W, or 270 mg Q2W- or placebo for 1 y LS BMD increase: 8.4% with 180 mg Q4W, 14.9% with 180 mg Q2W, 17.7% with 270 mg Q2W (P < .001 vs placebo for all) P1NP: significant increase with single and multiple doses, peaking from 1 to 3 mo, returning to baseline levels within 6 mo CTX: decreased with single and multiple doses, returning to baseline after treatments Prior bisphosphonate use did not impact blosozumab effect TH BMD increase: 2.1% with 180 mg Q4W (P < .05), 4.5% with 180 mg Q2W (P < .001), 6.7% with 270 mg Q2W (P < .001) vs placebo P1NP: rapid and robust increase peaking within 4 wk, returning to baseline levels within 1 y CTX: decreased to < placebo by 2 wk, similar to placebo at 12 wk, < placebo at 1 y Mild injection site reactions were higher in blosozumab patients than placebo Extension of phase 2 study [Recknor CP et al. J Bone Miner Res. 2015] Effect of blosozumab discontinuation 1 y after end of treatment in PM women with low BMD (n = 120) 106 patients completed treatment and continued into follow-up; 88 completed 1 y of follow-up LS and TH BMD declined but remained significantly higher vs placebo in 270 mg Q2W group and 180 mg Q2W P1NP and CTX remained at baseline levels ALN, alendronate; BAP, bone alkaline phosphatase; BMD, bone mineral density; CTX, carboxyterminal telopeptides of collagen 1; FN, femoral neck; IV, intravenous; LS, lumbar spine; P1NP, aminoterminal telopeptides of procollagen 1; PM, postmenopausal; Q2W, every 2 wk; Q4W, every 4 wk; QM, monthly; SC, subcutaneous; TH, total hip; TPT, teriparatide. Official Peer-Reviewed Highlights From ENDO 2015 21

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MD Conference Express - ENDO 2015