Safety and Efficacy of Burosumab in Children with X-Linked Hypophosphatemia

Patients with X-linked hypophosphatemia (XLH) have an excess of fibroblast growth factor-23 (FGF23), which leads to skeletal deformities and other clinical symptoms. Recently, the monoclonal antibody burosumab was approved to treat children and adult patients with XLH. In a study published in the Journal of Endocrinology and Metabolism, lead author Agnès Linglart and colleagues presented additional outcome data of burosumab, stating that, “in children with XLH, burosumab administration for 160 weeks improved phosphate homeostasis and rickets and was well-tolerated.”

This report was a follow up to the authors’ previous report, which reported outcomes in patients up to week 64. The randomized, dose-finding trial of burosumab for children aged 5 to 12 years enrolled a total of 26 children. The children were randomized 1:1 to burosumab treatment every two weeks (Q2W) or every four weeks (Q4W) for 64 weeks. Dosing was titrated based on fasting serum phosphorous levels at baseline and at week 16. After week 66, all patients received Q2W burosumab.

According to the report, all 26 patients completed treatment to week 160. The authors observed that, among 41 children from both groups with open distal femoral and proximal tibial growth plates, the total Rickets Severity Score decreased significantly by 0.9 ± 0.1 (least squares mean ± SE; p <0.0001) from baseline to week 160. Furthermore, the increases in fasting serum phosphorous levels were maintained during the duration of burosumab therapy, “with an overall population mean of 3.35 mg/dL,” which was within the normal range of 3.2 to 6.1 mg/dL at week 160 (p <0.0001).

Overall, the authors judged that burosumab therapy over more than three years yielded “clinically meaningful improvements across several clinical outcomes and demonstrated an acceptable benefit-risk profile” that was consistent with previous reports.