ESPN 51th Annual Meeting

ESPN 2018

Burosumab, a Fully Human Anti-FGF23 Monoclonal Antibody, for X-Linked Hypophosphatemia (XLH): Results from Two Phase 2 Trials in Affected Children 1-12 Years Old
William VantHoff 1 Michael P. Whyte 2 Erik Imel 3 Anthony A. Portale 4 Annemieke Boot 5 Wolfgang Hogler 6 Agnes Linglart 7 Raja Padidela 8 Gary S. Gottesman 2 Meng Mao 9 Alison Skrinar 9 Javier San Martin 9 Thomas O. Carpenter 10

1- Great Ormond Street Hospital, London, UK
2- Shriners Hospitals for Children, St Louis, MO, USA
3- Indiana University School of Medicine, Indianapolis, IN, USA
4- University of California, San Francisco, San Francisco, California, CA, USA
5- University of Groningen, Groningen, Netherlands
6- Birmingham Childrens Hospital, Birmingham, UK
7- APHP Hôpital Bicêtre Paris Sud
8- Royal Manchester Childrens Hospital, Manchester, UK
9- Ultragenyx Pharmaceutical Inc., Novato, California, USA
10- Yale School of Medicine, New Haven, CT, USA

 We investigated the efficacy and safety of subcutaneous burosumab, a fully human monoclonal antibody against FGF23, in children with XLH in two Phase 2 studies.

Material and methods:

In CL201, 52 children with XLH (5-12 years old, Tanner ≤ 2) were randomized 1:1 to receive burosumab every two (Q2W) or four (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 (1-4 years old) received burosumab 0.8 mg/kg Q2W, increased to 1.2 mg/kg based on serum phosphorus levels. 


Results are reported for Q2W-treated subjects (CL201 n=26; CL205 n=13). Collectively, 95% of subjects had prior conventional therapy. Rickets was evident at baseline in both studies (mean ± SE Thacher Rickets Severity Score [RSS]: CL201, 1.9 ± 0.2; CL205, 2.9 ± 0.4). At week 64, Total RSS fell by 58% CL201 and by 69% in CL205 (both p<0.0001). Mean (SD) dose (mg/kg) at week 64 was 1.04 (0.48) and 0.93 (0.18) for CL201 and CL205, respectively. Mean (SD) 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 in each study experienced a serious adverse event: hospitalization for fever/muscle pain that resolved within a day (CL201) and a dental abscess (CL205). Other adverse events were generally mild to moderate in severity. No clinically meaningful changes in calcium or iPTH were observed. No subjects discontinued the study or developed hyperphosphatemia. 


 Children with XLH, administered burosumab Q2W showed significant improvements in phosphate homeostasis and rickets that were maintained for over a year.