Burosumab Improved Histomorphometric Measures of Osteomalacia in Adults with X-Linked Hypophosphatemia: A Phase 3, Single-Arm, International Trial

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
K InsognaAnthony A Portale

Abstract

In adults with X-linked hypophosphatemia (XLH), excess FGF23 impairs renal phosphate reabsorption and suppresses production of 1,25-dihydroxyvitamin D, resulting in chronic hypophosphatemia and persistent osteomalacia. Osteomalacia is associated with poor bone quality causing atraumatic fractures, pseudofractures, delayed fracture healing, and bone pain. Burosumab is a fully human monoclonal antibody against FGF23. UX023-CL304 is an ongoing, open-label, single-arm, phase 3 study investigating the efficacy of subcutaneous burosumab, 1.0 mg/kg administered every 4 weeks, in improving osteomalacia in adults with XLH who have not been treated for at least 2 years before enrollment. The primary endpoint was improvement in osteoid volume/bone volume assessed by transiliac bone biopsies obtained at baseline and week 48. Additional assessments included serum phosphorus, markers of bone turnover, fracture/pseudofracture healing, and safety. Fourteen subjects enrolled, 13 completed 48 weeks, and 11 completed paired biopsies. All osteomalacia-related histomorphometric measures improved significantly at week 48 (mean percent change: osteoid volume/bone volume, -54%, osteoid thickness, -32%, osteoid surface/bone surface, -26%, [median] mine...Continue Reading

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Citations

Feb 13, 2020·The Journal of Clinical Endocrinology and Metabolism·Amy SteeleCarolyn M Macica
Jul 24, 2020·Current Opinion in Nephrology and Hypertension·Shanthi Balani, Farzana Perwad
Aug 29, 2020·Current Diabetes Reports·Stanley M H YeungMartin H De Borst
Jan 30, 2020·Wiener medizinische Wochenschrift·Adalbert RaimannRudolf Ganger
Apr 25, 2020·Calcified Tissue International·Erik Allen Imel
Jun 7, 2020·Calcified Tissue International·Diana Athonvarangkul, Karl L Insogna
Feb 27, 2020·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Anne-Lise LecoqPeter Kamenický
Sep 24, 2020·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Yasuo ImanishiSeiji Fukumoto
Dec 19, 2020·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Suzanne M Jan de BeurThomas O Carpenter
Nov 19, 2020·Journal of the Endocrine Society·Kathryn DahirJill H Simmons
Mar 19, 2021·Blood·Laura M Calvi
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Sep 16, 2021·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Maximilian M DelsmannTim Rolvien
Oct 13, 2021·The Journal of Clinical Endocrinology and Metabolism·Muhammad Kassim JavaidErik A Imel

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Methods Mentioned

BETA
biopsies
biopsy
florescence microscopy

Clinical Trials Mentioned

NCT02537431
NCT02526160

Software Mentioned

SAS

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