ESPE Abstracts (2019) 92 FC2.1

Continued Improvement in Clinical Outcomes with Burosumab, a Fully Human Anti-FGF23 Monoclonal Antibody: Results from a 3-Year, Phase 2, Clinical Trial in Children with X-Linked Hypophosphatemia (XLH)

Agnès Linglart1, Thomas O. Carpenter2, Wolfgang Högler3, Erik A. Imel4, Anthony A. Portale5, Annemieke Boot6, Raja Padidela7, William Van't Hoff8, Meng Mao9, Alison Skrinar9, Mary Scott Roberts9, Javier San Martin9, Michael P. Whyte10


1APHP Hôpital Bicêtre Paris Sud, New Haven, France. 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. 6University of Groningen, Groningen, Netherlands. 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 previously reported that burosumab improved phosphate homeostasis and rickets in children with XLH. Here, we report final data from this Phase 2 Study CL201 (NCT02163577).

Fifty-two children with XLH (5-12 years old, Tanner ≤ 2) were randomized 1:1 to receive subcutaneous burosumab every 2 (Q2W) or 4 (Q4W) weeks for 64 weeks. All subjects entered the long-term extension at Week 64, in which the Q4W group switched to Q2W, and completed the study (≥160 Weeks).

After Q4W switched to Q2W at Week 64, results between groups were similar by Week 88 and combined for the Week 160 analysis. Nearly all (50/52, 96%) subjects achieved a normal serum phosphorus level (3.2-6.1 mg/dL) by Week 160. Decreases in total Rickets Severity Score at Week 64, were maintained, with an LS mean ± SE change from baseline to Week 160 of -0.9 ± 0.1 (P<0.0001) in 42 subjects with open growth plates (11 had closed growth plates at distal femur and proximal tibia). Improvement in the Radiographic Global Impression of Change (RGI-C; N=42) global score observed at Week 88 (+1.6 ± 0.1) was maintained at Week 160 (+1.7 ± 0.1, P<0.0001). RGI-C lower limb deformity score continued to improve (Week 88: +0.6 ± 0.1, P<0.0001; Week 160: +1.1 ± 0.1, P<0.0001). Improvements in height Z-score at Week 160 (LS mean increase ± SE: Q2W +0.35 ± 0.08, Q4W→Q2W +0.19 ± 0.09) were almost doubled compared to Week 64 (Q2W +0.20 ± 0.05, Q4W→Q2W +0.11 ± 0.06). Increases in 6-Minute Walk distance observed at Week 64 were maintained through Week 160. Sports/Physical functioning and Pain/Comfort scores significantly improved from below normal at baseline to within the normal range at Week 160 (both P<0.0001). One subject had 2 AEs (fever/muscle pain and headache) classified as serious due to brief hospitalization; both resolved within a week. Other AEs were generally mild to moderate in severity. Change from baseline to Week 160 in nephrocalcinosis score was 0 in 39 subjects, +1 in 9 subjects, +2 in 1 subject, and -1 in 3 subjects. No noteworthy changes in serum calcium or PTH occurred. No subject developed hyperphosphatemia.

Long-term burosumab in children with XLH was associated with continued improvement in rickets, leg deformities, growth, and pain scores, as well as sustained improvement in mobility and normalization of phosphate homeostasis.