ICCBH2019 Oral Communications (1) (27 abstracts)
Sustained efficacy and safety of burosumab, a fully human anti-FGF23 monoclonal antibody, in children and early adolescents with X-linked hypophosphatemia
Wolfgang Högler 1 , Thomas Carpenter 2 , Erik Imel 3 , Anthony Portale 4 , Annemieke Boot 5 , Agnès Linglart 6 , Raja Padidela 7 , William van’t Hoff 8 , Meng Mao 9 , Alison Skrinar 9 , Javier San Martin 9 & Michael Whyte 10
1Johannes Kepler University Linz, Linz, Austria; 2Yale School of Medicine, New Haven, CT, USA; 3Indiana University School of Medicine, Indianapolis, IN, USA; 4University of California, San Francisco, San Francisco, CA, USA; 5University of Groningen, Groningen, the Netherlands; 6APHP Hôpital Bicêtre, Le Kremlin-Bicêtre, France; 7Royal Manchester Children’s Hospital, Manchester, UK; 8Great Ormond Street Hospital, London, UK; 9Ultragenyx Pharmaceutical Inc., Novato, CA, USA; 10Shriners Hospital for Children and Washington University School of Medicine, St Louis, MI, USA.
Objective: We evaluated the long-term efficacy of burosumab, a monoclonal antibody against FGF23, in a Phase 2 Study (NCT02163577) in children with XLH.
Methods: Fifty-two children with XLH (5-12 years-old, Tanner ≤ 2) were randomized 1:1 to receive subcutaneous burosumab Q2W or Q4W for 64 weeks. Doses were titrated up to 2 mg/kg/dose targeting serum phosphorus levels within 1.1–1.6 mmol/l. All subjects entered the long-term extension at Week 64, in which Q4W-treated subjects changed to Q2W; treatment continued through Week 88. Data through Week 160 will be available at the time of presentation. The significant improvements in rickets severity observed with the Radiographic Global Impression of Change (RGI-C) at Week 64 (LS mean±SE: Q2W+1.56±0.11, Q4W+1.58±0.11) were maintained through Week 88 (Q2W+1.67±0.14, Q4W→Q2W+1.85±0.09). Thirteen (50%) and 16 (62%) Q4W→Q2W subjects had a RGI-C ≥+2.0 by Week 64 and 88, respectively. Improvements observed at Week 64 in height Z-score (LS mean change±SE: Q2W+0.19±0.05, Q4W+0.12±0.06) and the 6-Minute Walk Test (Q2W+53±9 meters, Q4W+41±10 meters) were sustained through Week 88 (height Z-score: Q2W+0.26±0.05, Q4W→Q2W+0.15±0.06; 6MWT: Q2W+65±11 meters, Q4W→Q2W+44±12 meters). Significant increases in serum phosphorus were maintained through Week 88 (mean [SD] mmol/l: Q2W 1.1 [0.1]; Q4W→Q2W 1.1 [0.1]). For the 9 subjects who transitioned into adolescence (ranging from ~12 years-old at baseline to ~14 years-old at Week 88), improvements in serum phosphorus and rickets severity were maintained. One subject had concurrent serious AEs (fever/muscle pain) which resolved within a day. Other AEs were generally mild to moderate in severity; no new serious AEs emerged between Weeks 64–88. No clinically meaningful changes in serum calcium or iPTH occurred. No subject discontinued therapy or developed hyperphosphatemia.
Conclusion: Long-term burosumab treatment maintained improvements in clinical outcomes, including rickets severity, growth, and mobility in children and early adolescents with XLH. Children that changed from the Q4W to Q2W regimen at Week 64 showed additional improvement in rickets severity.
Disclosure: WH, TC, EI, AP, AB, AL, RP, WvH, and MW served as clinical investigators for this study, sponsored by Ultragenyx Pharmaceutical Inc. MM, AS, and JSM are employees and shareholder of Ultragenyx Pharmaceutical Inc.
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