ESPE Abstracts (2019) 92 FC2.2

Benefits of Long-Term Burosumab Persist in 11 Girls with X-Linked Hypophosphatemia (XLH) Who Transitioned into Adolescence During the Phase 2 CL201 Trial

Annemieke Boot1, Thomas O. Carpenter2, Wolfgang Högler3, Erik A. Imel4, Anthony A. Portale5, Agnès Linglart6, Raja Padidela7, William Van't Hoff8, Meng Mao 9, Alison Skrinar9, Mary Scott Roberts9, Javier San Martin9, Michael P. Whyte10


1University of Groningen, New Haven, Netherlands. 2Yale School of Medicine, New Haven, USA. 3Johannes Kepler University Linz, Linz, Austria. 4Indiana University School of Medicine, Indianapolis, USA. 5University of California, San Francisco, San Francisco, USA. 6APHP Hôpital Bicêtre Paris Sud, Le Kremlin-Bicêtre, France. 7Royal Manchester Children's Hospital, Manchester, United Kingdom. 8Great Ormond Street Hospital, London, United Kingdom. 9Ultragenyx Pharmaceutical Inc, Novato, USA. 10Shriners Hospital for Children and Washington University School of Medicine, St. Louis, USA


In children with XLH, excess FGF23 causes hypophosphatemia with consequent rickets, skeletal deformities, and impaired growth and mobility. We reported that burosumab improved phosphate homeostasis and rickets in children with XLH. Here, we present data on 11/52 subjects (all girls) who developed fused growth plates during the phase 2 study CL201 (NCT02163577).

In CL201, 52 subjects (Baseline: 5-12 years-old, Tanner ≤ 2) were randomized 1:1 to receive burosumab subcutaneously Q2W or Q4W for 64 weeks. All entered the long-term extension at Week 64, in which the Q4W group switched to Q2W, and completed ≥160 weeks.

Among the 52 subjects, 11 girls developed fused growth plates at the distal femur and proximal tibia (mean age: baseline 9.8 years, Week 160 13.3 years; mean Tanner stage: baseline 1.5, Week 160 3.4). Serum phosphorus levels for these 11 girls were maintained near the lower limit of normal (3.2 mg/dL) throughout the study. For the 10/11 girls whose last visit with open growth plates was Week 88, mean total Rickets Severity Score (RSS) decreased from 2.1 at baseline to 0.4 at Week 88, and the mean Week 88 Radiographic Global Impression of Change (RGI-C) was +2.3, both indicating improved rickets. Similarly, for the 1 girl whose last visit with open growth plates was Week 64, RSS decreased to 0 from 1.5 at baseline, with a Week 64 RGI-C of +2.7. In these 11 girls, LS mean RGI-C lower limb deformity score improved: +0.4 at Week 64 and +1.1 at Week 160. Standing height Z-score improved from a mean (SD) of -1.7 (0.9) at baseline to -1.5 (1.0) at Week 160. Mean sports/physical functioning and pain/comfort scores improved from below population norms at baseline to within population norms at Week 160. All adverse events (AEs) in these girls were mild or moderate in severity and most related-AEs were injection site reactions. At Week 160, nephrocalcinosis scores were unchanged from baseline in 10 subjects and 1-point lower in 1 subject. No clinically meaningful changes in serum calcium or PTH occurred. None of these girls developed hyperphosphatemia.

Benefits persisted with long-term burosumab in these 11 girls with XLH who developed fused growth plates during this study, including sustained improvements in phosphate metabolism, resolving rickets (assessed with open growth plates), better physical functioning, and less pain. These patients also showed continued improvement in leg deformities and growth.