ESPE Abstracts (2018) 89 FC2.1

Burosumab, a Fully Human anti-FGF23 Monoclonal Antibody, for X-linked Hypophosphatemia (XLH): Sustained Improvement in two Phase 2 Trials in Affected Children 1-12 years old

Agnès Linglarta, William van’t Hoffb, Michael P. Whytec, Erik Imeld, Anthony A. Portalee, Annemieke Bootf, Wolfgang Höglerg, Raja Padidelah, Meng Maoi, Alison Skrinari, Javier San Martini & Thomas O. Carpenterj


aAPHP Hôpital Bicêtre Paris Sud, Paris, USA; bGreat Ormond Street Hospital, London, UK; cShriners Hospitals for Children, St. Louis, Missouri, USA; dIndiana University School of Medicine, Indianapolis, Indiana, USA; eUniversity of California, San Francisco, California, USA; fUniversity of Groningen, Groningen, Netherlands; gBirmingham Children’s Hospital, Birmingham, UK; hRoyal Manchester Children’s Hospital, Manchester, UK; iUltragenyx Pharmaceutical Inc., Novato, California, USA; jYale School of Medicine, New Haven, Connecticut, USA


In XLH, excess fibroblast growth factor 23 (FGF23) causes hypophosphatemia and consequent rickets, skeletal deformities, and growth impairment. The efficacy and safety of burosumab, a fully human monoclonal antibody against FGF23, was evaluated in two Phase 2 trials in children with XLH. In CL201, 52 children with XLH (5–12 years old, Tanner ≤2) were randomized 1:1 to receive subcutaneous burosumab every 2 (Q2W) or 4 (Q4W) weeks, with doses titrated up to 2 mg/kg to target fasting serum phosphorus levels within 1.1–1.6 mmol/l. In CL205, 13 children with XLH (ages 1–4 years) received subcutaneous burosumab 0.8 mg/kg Q2W, which was increased to 1.2 mg/kg based on serum phosphorus levels. A key efficacy endpoint for each study was change in rickets severity assessed by blinded readers using two radiographic scales: Thacher Rickets Severity Score (RSS) and the Radiographic Global Impression of Change (RGI-C). Here, we present efficacy and safety data of Q2W dosing through week 64 from these studies. Results are reported for Q2W-treated subjects (CL201 n=26; CL205 n=13). Collectively, 95% of subjects had received prior conventional therapy. Rickets was evident at baseline in both studies (mean±SE RSS: CL201, 1.9±0.2; CL205, 2.9±0.4). At Week 64, Total RSS was reduced by 58% CL201 and by 69% in CL205 (both P<0.0001); rickets as assessed by RGI-C at Week 64 improved as well (CL201:+1.62±0.16, P<0.0001; CL205:+2.23±0.12, P<0.0001). Mean (S.D.) dose (mg/kg) at Week 64 was 1.04 (0.48) and 0.93 (0.18) for CL201 and CL205, respectively. Mean (S.D.) serum phosphorus (mmol/l) increased from 0.8 (0.1) at Baseline to 1.1 (0.1) at Week 64 in CL201 (P<0.0001); and from 0.8 (0.1) to 1.1 (0.2) in CL205 (P<0.0001). Mean alkaline phosphatase (U/l) decreased from 462 U/l at Baseline to 354 U/l at Week 64 in CL201 (P<0.0001); and from 549 to 334 in CL205 (P<0.0001). One subject per study experienced a serious adverse event (AE): hospitalization for fever/muscle pain that resolved within a day (CL201) and a dental abscess (CL205). Other AEs were generally mild to moderate in severity. No clinically meaningful changes in calcium or parathyroid hormone were observed. No subjects discontinued the study or developed hyperphosphatemia. Children 1–12 years old with XLH administered burosumab Q2W showed significant improvements in phosphate homeostasis and rickets that were maintained for 64 weeks.