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Clinical Trial
. 2021 Apr;36(4):627-635.
doi: 10.1002/jbmr.4233. Epub 2021 Jan 12.

Burosumab for the Treatment of Tumor-Induced Osteomalacia

Affiliations
Clinical Trial

Burosumab for the Treatment of Tumor-Induced Osteomalacia

Suzanne M Jan de Beur et al. J Bone Miner Res. 2021 Apr.

Abstract

Tumor-induced osteomalacia (TIO) is caused by phosphaturic mesenchymal tumors producing fibroblast growth factor 23 (FGF23) and is characterized by impaired phosphate metabolism, skeletal health, and quality of life. UX023T-CL201 is an ongoing, open-label, phase 2 study investigating the safety and efficacy of burosumab, a fully human monoclonal antibody that inhibits FGF23, in adults with TIO or cutaneous skeletal hypophosphatemia syndrome (CSHS). Key endpoints were changes in serum phosphorus and osteomalacia assessed by transiliac bone biopsies at week 48. This report focuses on 14 patients with TIO, excluding two diagnosed with X-linked hypophosphatemia post-enrollment and one with CSHS. Serum phosphorus increased from baseline (0.52 mmol/L) and was maintained after dose titration from week 22 (0.91 mmol/L) to week 144 (0.82 mmol/L, p < 0.0001). Most measures of osteomalacia were improved at week 48: osteoid volume/bone, osteoid thickness, and mineralization lag time decreased; osteoid surface/bone surface showed no change. Of 249 fractures/pseudofractures detected across 14 patients at baseline, 33% were fully healed and 13% were partially healed at week 144. Patients reported a reduction in pain and fatigue and an increase in physical health. Two patients discontinued: one to treat an adverse event (AE) of neoplasm progression and one failed to meet dosing criteria (receiving minimal burosumab). Sixteen serious AEs occurred in seven patients, and there was one death; all serious AEs were considered unrelated to treatment. Nine patients had 16 treatment-related AEs; all were mild to moderate in severity. In adults with TIO, burosumab exhibited an acceptable safety profile and was associated with improvements in phosphate metabolism and osteomalacia. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research..

Keywords: BONE HISTOMORPHOMETRY; CLINICAL TRIALS; OSTEOMALACIA AND RICKETS; PTH/VIT D/FGF23; TUMOR-INDUCED BONE DISEASE.

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Figures

Fig 1
Fig 1
Pharmacodynamic assessments of (A) serum phosphorus; (B) renal tubular reabsorption of phosphate (TmP/GFR); (C) serum 1,25(OH)2D; and (D) serum bone‐specific alkaline phosphatase. Data are presented as mean ± standard deviation. Baseline data points are shown in black, endpoint of the dose interval data points are shown in green, and midpoint of the dose interval data points are shown in blue, with the exception of week 21 for 1,25(OH)2D shown in blue, which is neither the mid‐ nor endpoint of the dose cycle. Assessments in mass units are available in Supplemental Fig. S2.
Fig 2
Fig 2
Histomorphometric and fracture assessments. Histomorphometric data (A) are presented as median, interquartile, 1.5× interquartile range, mean (+), and individual data points (○); for mineralization lag time, individual data points that were calculated using imputation are shown (∆); (13) *p < .05. Gray line indicates upper limit of normal reference ranges for osteoid volume/bone volume 3.05%, osteoid thickness 8.9 μm, mineralization lag time 28.6 days, and osteoid surface/bone surface 23.9%, and are from Glorieux and colleagues.( 11 ) Fracture healing data (B) are presented as number and percentage of baseline fractures and pseudofractures. A total of 20 (8.03%) and 48 (19.3%) fractures and pseudofractures that were identified at baseline were considered not readable or were not evaluated at weeks 96 and 144, respectively. Zoomed‐in image of chest from a full‐body bone scan (C) demonstrates multiple fractures/pseudofractures at baseline with reduction in fractures/pseudofractures at week 144.

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References

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