Open this publication in new window or tab >>Shriners Hospitals for Children St Louis, St Louis MO, United States.
Faculty of Medicine, The University of Queensland, Brisbane Queensland, Australia; Faculty of Medicine, Child Health Research Centre, The University of Queensland, Brisbane Queensland, Australia; Department of Endocrinology and Diabetes, Queensland Children’s Hospital, Brisbane Queensland, Australia.
Örebro University, School of Medical Sciences. Division of Pediatric Endocrinology, Department of Women’s and Children’s Health, Center for Molecular Medicine, Karolinska Institutet and University Hospital, Stockholm, Sweden; Department of Pediatrics, School of Medical Sciences, Örebro University and University Hospital, Örebro, Sweden.
Division of Endocrinology and Diabetes, Department of Pediatrics, Vanderbilt University School of Medicine, Vanderbilt University, Nashville TN, United States.
Department of Paediatric Endocrinology, Royal Manchester Children’s Hospital, Manchester, United Kingdom.
Department of Pediatrics, Osaka Hospital, Japan Community Healthcare Organization, Osaka, Japan; Osaka University Graduate School of Medicine, Osaka, Japan.
Department of Pediatrics, Hallym University Sacred Heart Hospital, Dongan-gu, Anyang, South Korea.
Department of Pediatrics, Hospital for Sick Children, Toronto Ontario, Canada.
Department of Endocrinology, Kanagawa Children’s Medical Center, Yokohama, Kanagawa Japan.
Division of Pediatrics, Okayama Saiseikai General Hospital Outpatient Center, Kita-ku, Okayama, Japan.
Center of Endocrinology, Diabetes and Metabolism, Children’s Hospital of Los Angeles, Los Angeles CA, United States.
Shriners Hospitals for Children St Louis, St Louis MO, United States.
Department of Endocrinology, The University of Sydney Children’s Hospital Westmead Clinical School, The Children’s Hospital at Westmead, Westmead New South Wales, Australia.
Department of Pediatrics, University of California, San Francisco CA, United States.
Ultragenyx Pharmaceutical Inc., Novato CA, United States.
Ultragenyx Pharmaceutical Inc., Novato CA, United States.
Department of Medicine, Indiana University School of Medicine, Indianapolis IN, United States.
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2024 (English)In: JBMR Plus, E-ISSN 2473-4039, Vol. 8, no 1, article id ziad001Article in journal (Refereed) Published
Abstract [en]
In a randomized, open-label phase 3 study of 61 children aged 1-12 years old with X-linked hypophosphatemia (XLH) previously treated with conventional therapy, changing to burosumab every 2 weeks (Q2W) for 64 weeks improved the phosphate metabolism, radiographic rickets, and growth compared with conventional therapy. In this open-label extension period (weeks 64-88), 21 children continued burosumab Q2W at the previous dose or crossed over from conventional therapy to burosumab starting at 0.8 mg/kg Q2W with continued clinical radiographic assessments through week 88. Efficacy endpoints and safety observations were summarized descriptively for both groups (burosumab continuation, n = 6; crossover, n = 15). At week 88 compared with baseline, improvements in the following outcomes were observed in the burosumab continuation and crossover groups, respectively: mean (SD) RGI-C rickets total score (primary outcome), +2.11 (0.27) and +1.89 (0.35); mean (SD) RGI-C lower limb deformity score, +1.61 (0.91) and +0.73 (0.82); and mean (SD) height Z-score + 0.41 (0.50) and +0.08 (0.34). Phosphate metabolism normalized rapidly in the crossover group and persisted in the continuation group. Mean (SD) serum alkaline phosphatase decreased from 169% (43%) of the upper limit of normal (ULN) at baseline to 126% (51%) at week 88 in the continuation group and from 157% (33%) of the ULN at baseline to 111% (23%) at week 88 in the crossover group. During the extension period, treatment-emergent adverse events (AEs) were reported in all 6 children in the burosumab continuation group and 14/15 children in the crossover group. The AE profiles in the randomized and extension periods were similar, with no new safety signals identified. Improvements from baseline in radiographic rickets continued in the extension period among children with XLH who remained on burosumab. Children who crossed over from conventional therapy to burosumab demonstrated a rapid improvement in phosphate metabolism and improved rickets healing over the ensuing 22 weeks.
Place, publisher, year, edition, pages
Oxford University Press, 2024
Keywords
burosumab, FGF23, phosphate, rare disease, x-linked hypophosphatemia
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:oru:diva-113457 (URN)10.1093/jbmrpl/ziad001 (DOI)001203133400006 ()38690124 (PubMedID)2-s2.0-85193424229 (Scopus ID)
Note
This study was sponsored and funded by Ultragenyx Pharmaceutical Inc. in partnership with Kyowa Kirin International plc. Medical writing support was provided by Ben Scott, PhD (Scott Medical Communications, LLC) and was funded by Ultragenyx Pharmaceutical Inc. Additional editorial support was provided by Jamie Ziobro, an employee and share holder of Ultragenyx Pharmaceutical Inc. At Indiana University, the research was done at the Indiana Clinical and Translational Sciences Institute, funded in part by UL1TR002529 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical, and Translational Sciences Award. In Montreal and St. Louis, the work was also supported by the Shriners of North America. Dr. Ward is supported by a Tier 1 (Senior) Research Chair in Pediatric Bone Disorders from the University of Ottawa and Children's Hospital of Eastern Ontario Research Institute.
2024-04-302024-04-302025-01-20Bibliographically approved