A phase 2 trial of burosumab for treatment of fibroblast growth factor-23 mediated hypophosphatemia in children and adults with fibrous dysplasia

Sep 28, 2026

Fibrous dysplasia (FD) is a rare disorder linked to fractures and deformities. FD lesions overproduce fibroblast growth factor 23 (FGF23), causing hyperphosphaturia in many patients and hypophosphatemia in those with higher FD burden, which is associated with skeletal complications. A phase 2 study evaluated burosumab targeting this pathway; 12 participants received treatment for 48 weeks. Results showed phosphate Z-score normalization in all participants, mild adverse events without withdrawal, improved bone turnover, and no adverse effects on lesion activity by biopsy or 18F-NaF PET/CT.

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CategoryHealthcare

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Abstract

Introduction

medRxiv preprint doi: [https://doi.org/10.1101/2025.09.26.25334161](https://doi.org/10.1101/2025.09.26.25334161); this version posted October 2, 2025. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. A phase 2 trial of burosumab for treatment of fibroblast growth factor-23 mediated hypophosphatemia in children and adults with fibrous dysplasia Olivia de Jong 1 , Zubeyir Hasan Gun 1 , Afua Asante-Otoo2 , Ibrahim Elbashir1 , Xiaobai Li3 , Babak Saboury4 , Vardit Kram 1 , Luis F de Castro 1 , Vivian MacDonald1 , Alison M Boyce 1 1 Metabolic Bone Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA 2 Rehabilitation Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA 3 Biostatistics and Clinical Epidemiology Service, Clinical Center, National Institutes of Health, Bethesda, MD, USA 4 Institute of Nuclear Medicine, Bethesda, MD, USA Correspondence to: Alison Boyce, MD Building 30 Room 228 MSC 4320 Bethesda, MD, 20892 [alison.boyce@nih.gov](alison.boyce@nih.gov) ABSTRACT Fibrous dysplasia (FD) is a rare disorder associated with fractures and deformities. FD lesions produce excess phosphaturic hormone fibroblast growth factor 23 (FGF23), leading to hyperphosphaturia in most patients, and hypophosphatemia in those with high FD burden. Skeletal complications are associated with both low-normophosphatemia and frank hypophosphatemia. Burosumab is approved for other forms of FGF23 excess, but there is little evidence to inform use in FD. A phase 2 study investigated the safety and efficacy of NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: [https://doi.org/10.1101/2025.09.26.25334161](https://doi.org/10.1101/2025.09.26.25334161); this version posted October 2, 2025. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. burosumab in patients with FD. The primary endpoint was the proportion of participants achieving phosphate levels within a high-normal target range (age and sex-adjusted Z-score –1 to +2) . 12 participants (7 children, 5 adults) received burosumab for 48 weeks. Median phosphate Z-score increased from-2.88 (1 .65) to 0.22 (1 .37), meeting the target in 100% of participants. Alkaline phosphatase levels were elevated at baseline in 8 participants and declined by 49% . PROMIS questionnaires showed trends toward improvements in all domainsin children; adult scores showed no identifiable trends. Two children experienced transformational mobility gains, including advancement from full-time wheelchair use to independent ambulation. Lesion biopsies showed no changes in cellularity or composition, and 18 F-NaF PET/CT scans showed no changes in tracer uptake, suggesting burosumab did not adversely impact lesional activity. Adverse events were mild, and none resulted in treatment withdrawal. Burosumab targeting high-normophosphatemia in patients with FD was welltolerated, restored phosphate homeostasis, and improved bone turnover. Burosumab has the potential to lead to functional improvements and ambulation gains in severely affected patients and is a valuable tool to reduce the impact of FD-related disability. INTRODUCTION Fibrous dysplasia (FD) is a rare mosaic disorder associated with fractures, pain, and skeletal deformities. It may affect one or multiple bon

FAQs

What condition and mechanism does the study target?

The study targets fibrous dysplasia, where lesions produce excess FGF23, leading to phosphate wasting and hypophosphatemia in some patients.

What was the primary endpoint and what did the trial show?

The primary endpoint was the proportion achieving phosphate levels in a high-normal target range (age- and sex-adjusted Z-score -1 to +2). All 12 participants met the target after 48 weeks, with median phosphate Z-score increasing from -2.88 to 0.22.

How did burosumab affect safety and lesion activity?

Adverse events were mild and none led to treatment withdrawal. Biopsies and 18F-NaF PET/CT scans showed no changes suggesting burosumab did not adversely impact lesional cellular activity.

Sep 28, 2026

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