Sustained efficacy and safety of burosumab, a monoclonal antibody to FGF23, in children with X-linked hypophosphatemia.

Purpose In X-linked hypophosphatemia (XLH), excess FGF23 causes hypophosphatemia and low calcitriol, leading to musculoskeletal disease with clinical consequences. XLH treatment options include conventional oral phosphate with active vitamin D, or monotherapy with burosumab, a monoclonal antibody approved to treat children and adults with XLH. We have previously reported outcomes up to 64 weeks, and here, we report safety and efficacy follow-up results up to 160 weeks from an open-label, multicenter, randomized, dose-finding trial of burosumab for 5 to 12 year-old children with XLH. Methods After one week of conventional therapy washout, patients were randomized 1:1 to burosumab every 2 weeks (Q2W) or every 4 weeks (Q4W) for 64 weeks, with dosing titrated based on fasting serum phosphorus levels between baseline and Week 16. From Week 66 to Week 160, all patients received Q2W burosumab. Results Twenty-six children were randomized initially into each Q2W and Q4W group and all completed treatment to Week 160. In 41 children with open distal femoral and proximal tibial growth plates (from both treatment groups), total Rickets Severity Score significantly decreased by 0.9±0.1 (least squares mean±SE; p Main conclusions In children with XLH, burosumab administration for 160 weeks improved phosphate homeostasis and rickets and was welltolerated. Long-term safety was consistent with the reported safety profile of burosumab.