ICCBH2019 Oral Communications (1) (27 abstracts)
Burosumab resulted in greater improvement in clinical outcomes than continuation with conventional therapy in younger (1-4 years-old) and older (5-12 years-old) children with X-linked hypophosphatemia
Leanne Ward 1 , Erik Imel 2 , Michael Whyte 3 , Craig Munns 4 , Anthony Portale 5 , Wolfgang Högler 6 , Jill Simmons 7 , Raja Padidela 8 , Noriyuki Namba 9 , Hae Cheong 10 , Ola Nilsson 11 , Meng Mao 12 , Alison Skrinar 12 , Chao-Yin Chen 12 , Javier San Martin 12 & Francis Glorieux 13
1University of Ottawa, Ottawa, Canada; 2Indiana University School of Medicine, Indianapolis, IN, USA; 3Shriners Hospitals for Children, St Louis, St Louis, MI, USA; 4The Children’s Hospital at Westmead, Sydney, Australia; 5University of California, San Francisco, San Francisco, CA, USA; 6Johannes Kepler University Linz, Linz, Austria; 7Vanderbilt University School of Medicine, Nashville, TN, USA; 8Royal Manchester Children’s Hospital, Manchester, UK; 9Osaka Hospital, Japan Community Healthcare Organization and Osaka University Graduate School of Medicine, Osaka, Japan; 10Seoul National University Children’s Hospital, Seoul, Korea; 11Karolinska Institutet and University Hospital and Örebro University, Stockholm, Sweden; 12Ultragenyx Pharmaceutical Inc., Novato, CA, USA; 13Shriners Hospital for Children-Canada, McGill University, Montreal, Canada.
Objective: We compared the efficacy and safety of burosumab, a monoclonal antibody against FGF23, to conventional therapy [oral phosphate and active vitamin D (Pi/D)] in children with X-linked hypophosphatemia (XLH).
Methods: In this Phase 3 trial (NCT02915705), 61 children with XLH (1-12 years-old) were randomized 1:1 after a 7-day Pi/D washout to receive burosumab starting at 0.8 mg/kg SC Q2W or reinitiate Pi/D optimally titrated by investigators. Eligibility criteria included Rickets Severity Score ≥2.0 despite prior Pi/D treatment. Healing of rickets (primary endpoint) was assessed by radiologists blinded to treatment using the Radiographic Global Impression of Change (RGI-C) at Week 40. Lower limb deformity and growth were assessed at Week 64. In addition to comparing all subjects, we compared treatments in subjects < and ≥5 years-old.
Results: By Week 40, RGI-C was significantly higher with burosumab than with Pi/D (LS mean±SE: burosumab, +1.9±0.1 vs Pi/D+0.8±0.1; P<0.0001); RGI-C results were similar in subjects <5 years-old (burosumab, N=14,+1.9±0.2 versus Pi/D, N=12,+0.7±0.2) and ≥5 years-old (burosumab, N=15,+2.0±0.1 versus Pi/D, N=20,+0.9±0.1). Improvement in lower limb deformity score was greater with burosumab than Pi/D for all subjects (Week 64 LS mean±SE: +1.3±0.2 vs +0.3±0.1; P<0.0001), subjects <5 years-old (+1.5±0.3 vs +0.5±0.2), and subjects ≥5 years-old (+1.0±0.2 vs +0.1±0.1). Burosumab showed greater improvement than Pi/D in length/height Z-score for all subjects (Week 64 LS mean change±SE: +0.17±0.07 vs +0.02±0.04; P=0.0490), subjects <5 years-old (+0.15±0.12 vs -0.05±0.07), and subjects ≥5 years-old (+0.17±0.05 vs +0.08±0.04). Dental adverse events (AEs) and AEs of interest, including hypersensitivity and injection site reactions, were more frequent with burosumab, and were mild to moderate in severity overall. Three serious AEs occurred per group, all unrelated to treatment and resolved. No discontinuations occurred.
Conclusions: Both younger and older children with XLH demonstrated greater improvements in rickets, bowing, and growth after burosumab than those who continued with Pi/D.
Disclosure: LW, EI, MW, CM, AP, WH, JS, RP, NN, HC, ON, and FG served as clinical investigators for this study sponsored by Ultragenyx Pharmaceutical Inc. MM, AS, C-YC, and JSM are employees and shareholders of Ultragenyx Pharmaceutical Inc.
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