ECE2018 Oral Communications New insights in bone disorders (5 abstracts)
A Phase 3 randomized, double-blind, placebo-controlled study investigating the efficacy and safety of Burosumab, an anti-FGF23 antibody, in adult X-Linked Hypophosphatemia (XLH)
Peter Kamenický 1 , Robin Lachmann 2 , Thomas O. Carpenter 3 , Martine Cohen-Solal 4 , Richard Eastell 5 , Maria Luisa Brandi 6 , Rachel K. Crowley 7 , Stuart H. Ralston 8 , Muhammad K. Javaid 9 , Richard Keen 10 , Karine Briot 11 , Hae Il Cheong 12 , Yasuo Imanishi 13 , Nobuaki Ito 14 , Hiroyuki Tanaka 15 , Lin Zhang 16 , Christina Theodore-Oklota 16 , Matt Mealiffe 16 , Javier San Martin 16 & Karl L. Insogna 3
1Université Paris-Sud, Le Kremlin Bicêtre, France; 2University College London Hospitals, London, UK; 3Yale School of Medicine, New Haven, Connecticut, USA; 4Hôpital Lariboisière, 2 rue Ambroise Paré, Paris, France; 5University of Sheffield, Sheffield, UK; 6Azienda Ospedaliero Universitaria Careggi, Firenze, Italy; 7St Vincent’s University Hospital and University College, Dublin, Ireland; 8University of Edinburgh, Western General Hospital, Edinburgh, UK; 9NDORMS, University of Oxford, Oxford, UK; 10Royal National Orthopaedic Hospital, Stanmore, UK; 11Centre d’Evaluation des Maladies Osseuses, Hôpital Cochin, Paris, France; 12Seoul National University Children’s Hospital, Seoul, Republic of Korea; 13Osaka City University Graduate School of Medicine, Osaka, Japan; 14University of Tokyo, Tokyo, Japan; 15Okayama Saiseikai General Hospital, Oakayama, Japan; 16Ultragenyx Pharmaceutical Inc., Novato, California, USA.
UX023-CL303 is an ongoing, Phase 3, double-blind, multicenter study examining the efficacy and safety of burosumab, a fully human monoclonal antibody against FGF23, in adults with XLH. Eligible subjects had serum phosphorus levels <0.81 mmol/l and skeletal pain (BPI – Worst Pain ≥4). Subjects (N=134) were randomized 1:1 to receive burosumab 1 mg/kg or placebo subcutaneously every 4 weeks. After 24 weeks, subjects in the placebo group crossed-over to receive burosumab and all subjects continued treatment for an additional 24 weeks. A significantly greater percentage of subjects in the burosumab group attained the primary endpoint of mean serum phosphorus above the lower limit of normal (LLN) at the midpoint of the dosing intervals through week 24 compared with the placebo group (94.1% vs 7.6%; P<0.0001); increases were maintained between weeks 24–48 (crossover 89.4%, burosumab-only 83.8%). At baseline, 91 and 65 active fractures/pseudofractures (Fx/PFx) were present in 58% and 47% subjects in the crossover and burosumab-only group, respectively. At Week 24, 8% and 43% of Fx/PFx were healed after subjects received placebo and burosumab, respectively (odds ratio 16.8, P<0.0001). At Week 48, the burosumab-only group demonstrated additional Fx/PFx healing (63% Fx/PFx healed); the crossover group showed healing similar to that of the burosumab-only group at Week 24 (35%). For key secondary endpoints, burosumab had significantly greater decreases in stiffness score (−7.87±3.04 vs 0.25±3.13; P=0.012) than placebo at Week 24; and non-significant reductions in pain (LS mean change ± SE: burosumab −0.79±0.21 vs placebo −0.32±0.22; P=0.092) and physical functioning (−3.11±2.55 vs 1.79±2.72; P=0.048) scores. At Week 48, there were significant reductions from baseline (Week 24 for crossover) in stiffness (LS mean change ± SE: crossover −15.3±3.5, burosumab-only −16.0±3.3; both P<0.0001), physical functioning (crossover −6.4±2.9, burosumab-only −7.8±2.1; both P<0.001), and pain (crossover −1.5±0.2, burosumab-only −1.1±0.2; both P<0.0001) scores. Opioid use declined with burosumab (% subjects at Baseline, Week 24, Week 48: crossover 20%, 21%, 6%; burosumab-only 25%, 24%, 6%); NSAID use declined (crossover 65%, 58%, 17%; burosumab-only 69%, 63%, 19%). Fifteen subjects had serious AEs, none were drug-related. No meaningful changes in calcium, iPTH, or nephrocalcinosis scores occurred. Overall, burosumab was well tolerated in adults with XLH and associated with improvements in serum phosphorus, pain, stiffness, physical functioning, and Fx/PFx healing.
Volume 56
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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