ESPE Abstracts

Background: X-linked hypophosphatemia (XLH) is a rare, often debilitating genetic disorder caused by mutations in the phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) that is characterized by excess fibroblast growth factor 23 (FGF23), hypophosphatemia, skeletal deformities, and growth impairment.^1,2 Conventional therapy with the combination of phosphate and active vitamin D is associated with poor treatment adherence, high rate of failure and long-term adverse events.^2,3 Burosumab, a fully human IgG1 monoclonal anti FGF23 antibody, addresses the underlying physiopathology of XLH and demonstrates significant clinical improvement in children.^1,4 This study evaluates the effect of burosumab treatment in Saudi pediatric XLH patients previously on conventional therapy.

Methods: This observational, retrospective study analyzed the data of 6 pediatric XLH patients (median age of 8.8 years) collected from 3 centers [National Guard Hospital (Riyadh), King Faisal Specialist Hospital (Riyadh) and National Guard Hospital (Jeddah)] from 2018-2020. Biochemical parameters including serum phosphate, alkaline phosphatase (ALP) and tubular maximum re-absorption of phosphate to glomerular filtration rate (TmP/GFR) were collected at diagnosis; every month until 3 months, and every 3 months until 24 months into burosumab treatment. Burosumab was administered at a starting dose of 0.8 mg/kg and the dosing was increased at 3 months to 1.14 mg/kg and 1.07 mg/kg in two patients and at 6 months to 1.03 mg/kg in one patient.

Results: All burosumab-treated patients had increased serum phosphate and reduced ALP levels in the first year of treatment. Burosumab also led to improved TmP/GFR levels at 12 months, in 5 patients for which data was available. Four patients reported continuous improvement in the serum phosphate levels in the second year of burosumab treatment. Two patients reported initial serum phosphate improvement but presented with reduced levels after 21 months due to treatment compliance issues with episodic discontinuations related to the COVID-19 pandemic. The improvement in ALP levels was consistent for all patients throughout the burosumab treatment duration. No clinically significant safety findings were observed with burosumab.

Conclusion: This two-year experience demonstrates that treatment with burosumab led to marked improvement in the biochemical parameters of pediatric XLH patients in Saudi Arabia.

References: 1. Lyseng-Williamson KA. Drugs Ther Perspect. 2018; 34(11): 497–506. 2. Fujiwara M et al. Clin Pediatr Endocrinol. 2013;22(1): 9–14. 3. Linglart A et al. Endocr Connect. 2014;3(1): R13-30. 4. Kutilek S. Sudanese J Paediatr. 2017;17(2): 71-73.