ESPE Abstracts (2019) 92 RFC2.1

Burosumab Resulted in Better Clinical Outcomes Than Continuation with Conventional Therapy in Both Younger (1-4 Years-Old) and Older (5-12 Years-Old) Children with X-Linked Hypophosphatemia

Wolfgang Högler1, Erik A. Imel2, Michael P. Whyte3, Craig Munns4, Anthony A. Portale5, Leanne Ward6, Ola Nilsson7, Jill H. Simmons8, Raja Padidela9, Noriyuki Namba10, Hae Il Cheong11, Meng Mao12, Alison Skrinar12, Javier San Martin 12, Francis Glorieux13


1Johannes Kepler University Linz, Linz, Austria. 2Indiana University School of Medicine, Indianapolis, USA. 3Shriners Hospitals for Children, St. Louis, USA. 4The Children's Hospital at Westmead, Sydney, Australia. 5University of California, San Francisco, San Francisco, USA. 6University of Ottawa, Ontario, Canada. 7Karolinska Institutet, Stockholm, Sweden. 8Vanderbilt University School of Medicine, Nashville, USA. 9Royal Manchester Children's Hospital, Manchester, United Kingdom. 10Osaka Hospital, Japan Community, Healthcare Organization and Osaka University Graduate School of Medicine, Osaka, Japan. 11Seoul National University Children's Hospital, Seoul, Korea, Republic of. 12Ultragenyx Pharmaceutical Inc, Novato, USA. 13Shriners Hospital for Children-Canada, McGill University, Montreal, Canada


In children with X-linked hypophosphatemia (XLH), excess circulating fibroblast growth factor 23 (FGF23) causes hypophosphatemia with consequent rickets, skeletal deformities, and impairments in growth and mobility. Compared to continuation with conventional therapy (oral phosphate and active vitamin D [Pi/D]), switching to treatment with burosumab, a fully human monoclonal antibody against FGF23, showed significantly greater improvement in phosphate homeostasis, rickets severity, lower limb deformity, growth, and mobility in children with XLH. Here, we report a sub-analysis from the Phase 3 Study CL301 (NCT02915705), comparing these treatment groups in children with XLH < and ≥5 years-old.

Sixty-one 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 resume Pi/D titrated by their investigator. 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) Score at Week 40. Lower limb deformity and growth were assessed at Week 64.

By Week 40, RGI-C score was significantly higher with burosumab than with Pi/D (LS mean ± SE: burosumab, +1.9 ± 0.1 versus 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 versus +0.3 ± 0.1; P<0.0001), subjects <5 years-old (+1.5 ± 0.3 versus +0.5 ± 0.2), and subjects ≥5 years-old (+1.0 ± 0.2 versus +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 versus +0.02 ± 0.04; P=0.0490), subjects <5 years-old (+0.15 ± 0.12 versus -0.05 ± 0.07), and subjects ≥5 years-old (+0.17 ± 0.05 versus +0.08 ± 0.04). Dental adverse events (AEs) and AEs of interest identified from previous burosumab trials, 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.

Both younger and older children with XLH demonstrated greater improvements in rickets, bowing, and growth during burosumab than those who continued with Pi/D.