E-Poster Presentation 30th Australian and New Zealand Bone and Mineral Society Annual Scientific Meeting 2020

In Pediatric X-linked Hypophosphatemia (XLH), Burosumab Improved Clinical Outcomes Versus Higher and Lower Doses of Oral Phosphate and/or Active Vitamin D (#128)

Erik A Imel 1 , Francis H Glorieux 2 , Michael P Whyte 3 , Anthony A Portale 4 , Craig F Munns 5 , Ola Nilsson 6 , Jill H Simmons 7 , Raja Padidela 8 , Noriyuki Namba 9 10 , Hae II Cheong 11 , Pisit Pitukcheewanont 12 , Etienne Sochett 13 , Wolfgang Högler 14 , Koji Muroya 15 , Hiroyuki Tanaka 16 , Gary S Gottesman 3 , Andrew Biggin 5 , Farzana Perwad 4 , Angel Chen 17 , Mary Scott Roberts 17 , Leanne Ward 18
  1. Indiana University School of Medicine, Indianapolis, IN, United States
  2. Shriners Hospitals for Children, Montreal, Canada
  3. Shriners Hospitals for Children St Louis, St Louis, MO, United States
  4. Department of Pediatrics, University of California, San Francisco, CA, USA
  5. The Children's Hospital at Westmead, Westmead, NSW, Australia
  6. Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
  7. Department of Pediatrics, Division of Endocrinology and Diabetes, Vanderbilt University School of Medicine, Vanderbilt University, Nashville, TN, United States
  8. Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, Manchester, United Kingdom
  9. Osaka Hospital, Japan Community Healthcare Organization and Osaka University Graduate School of Medicine, Osaka, Japan
  10. Tottori University Faculty of Medicine, Yonago, Japan
  11. Seoul National University Children’s Hospital, Seoul, Korea
  12. Center of Endocrinology, Diabetes and Metabolism, Children's Hospital of Los Angeles, Los Angeles, CA, United States
  13. Department of Pediatrics, Hospital for Sick Children, Toronto, ON, Canada
  14. Department of Paediatrics and Adolescent Medicine, Johannes Kepler University Linz, Linz, Austria
  15. Kanagawa Children’s Medical Center, Yokohama, Japan
  16. Okayama Saiseikai General Hospital Outpatient Center, Okayama , Japan
  17. Ultragenyx Pharmaceutical Inc., Novato, CA, USA
  18. University of Ottawa, Ottawa, Ontario, Canada

In a phase 3 trial in children with XLH (CL301; NCT02915705), burosumab resulted in greater improvements in hypophosphatemia and related morbidities than continuation with oral phosphate and active vitamin D (Pi/D). Here, we present a post-hoc analysis assessing the response to burosumab vs higher or lower average daily doses of Pi/D over 64 weeks.

Children (1-12 years-old) with XLH receiving Pi/D with Rickets Severity Score ≥2.0 were randomized 1:1 to 64 weeks of burosumab starting at 0.8 mg/kg subcutaneously Q2W or to resume Pi/D. Pi/D dose categories were assessed as: phosphate >40 mg/kg (HPi), phosphate ≤40 mg/kg (LPi), alfacalcidol >60 ng/kg or calcitriol >30 ng/kg (HD), and alfacalcidol ≤60 ng/kg or calcitriol ≤30 ng/kg (LD). We used the Radiographic Global Impression of Change (RGI-C) to assess rickets healing at 64 weeks based on Pi/D dose categories before (pre-baseline) and during study.

The distribution of children in the Pi/D dose categories pre-baseline were: 8 HPi, 21 LPi, 7 HD, and 22 LD in the burosumab group (n=29), and 3 HPi, 29 LPi, 7 HD, and 25 LD in the Pi/D group (n=32). On-study, the distribution was 12 HPi, 20 LPi, 14 HD, and 18 LD in the Pi/D group.

Regardless of Pi/D doses administered pre-baseline, children receiving burosumab had an approximately two-fold greater improvement in least square (LS) mean RGI-C score for rickets healing vs those continuing Pi/D (Table). Further, at Week 64, the LS mean RGI-C score with burosumab (2.1 ±0.1) was greater vs on-study treatment with HPi (1.0 ±0.2), LPi (1.0 ±0.2), HD (1.5 ±0.2), or LD (0.7 ±0.2). The LS mean improvement in lower limb deformity RGI-C with burosumab (+1.3 ±0.2) was greater vs HPi (+0.3 ±0.2), LPi (+0.3 ±0.1), HD (+0.4 ±0.2), or LD (+0.2 ±0.1). The LS mean alkaline phosphatase (U/L) decrease from baseline with burosumab was ‑174 ±14 vs HPi (‑43 ±29), LPi (‑19 ±28), HD (‑59 ±30), or LD (‑4 ±24). The mean parathyroid hormone (PTH) percent change from baseline with burosumab was +10.5 ±13.3 vs HPi (+45.2 ±41.0), LPi (‑9.5 ±13.1), HD (‑29.3 ±15.5), or LD (+42.5 ±27.2). Adverse events on burosumab included mild to moderate hypersensitivity and injection site reactions. No discontinuations occurred.

In children with XLH, improvements in rickets, lower limb deformity, and decreases in ALP were greater during burosumab than with either higher or lower on-study doses of phosphate or active vitamin D. The increase in PTH was greatest in the HPi and LD groups.

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Disclosures

  • Leanne Ward has been a consultant to, and has received research support from, Ultragenyx (with funds to Dr. Ward’s institution)
  • Francis H. Glorieux has received consulting fees and research grants from Kyowa-Kirin and Ultragenyx Pharmaceutical Inc.
  • Michael P. Whyte received research grant support from Ultragenyx Pharmaceutical Inc.
  • Anthony A. Portale has received speakers’ honoraria and research support paid to his institution from Ultragenyx Pharmaceutical Inc.
  • Craig F. Munns has received research funding from Ultragenyx and Kyowa Kirin.
  • Ola Nilsson has received speakers’ honoraria from Lilly, Abbott, and Biomarin, consulting fees from Ascendis and KyowaKirin, and research support from KyowaKirin and the Novo Nordisk Foundation.
  • Jill H. Simmons has received research support from Ultragenyx Pharmaceutical Inc. paid to her institution.
  • Raja Padidela has been a consultant to, and has received research support from, Ultragenyx (with funds to Dr. Padidela’s institution)
  • Noriyuki Namba has received honoraria for serving as an advisory board member and for lectures from Kyowa Kirin.
  • Hae Il Cheong has no conflicts of interest to declare.
  • Pisit Pitukcheewanont has received grant/research support from Ultragenyx Pharmaceutical Inc., Amgen, Shire, and has been a consultant for Ultragenyx Pharmaceutical Inc., Ferring, Alexion, and is currently an employee of Ascendis Pharma Inc.
  • Etienne Sochett
  • Wolfgang Högler has received research grant support from Kyowa Kirin and has been a consultant to Ultragenyx Pharmaceutical Inc.
  • Koji Muroya
  • Hiroyuki Tanaka has no conflicts of interest to declare.
  • Gary S. Gottesman has no conflicts of interest to declare.
  • Andrew Biggin has no conflicts of interest to declare.
  • Farzana Perwad is a consultant for Ultragenyx Pharmaceutical Inc.
  • Angel Chen and Mary Scott Roberts: Employees and stockholders of Ultragenyx Pharmaceutical Inc.
  • Erik A. Imel has received research grant and has been a consultant to Ultragenyx Pharmaceutical Inc.