OR29-01 Long-Term Safety in Adults with X-Linked Hypophosphatemia (XLH) Treated with Burosumab, a Fully Human Monoclonal Antibody Against FGF23: Final Results of a Phase 3 Trial

Burosumab, a fully human IgG1 monoclonal antibody to FGF23, is approved in Canada and Brazil to treat XLH in patients ≥1 year of age and in the US to treat XLH in patients ≥6 months of age. Burosumab has also received conditional marketing authorization in Europe to treat XLH with radiographic evidence of bone disease in children ≥1 year of age and in adolescents with growing skeletons. Burosumab significantly improved serum phosphorus, fracture/pseudofracture healing, stiffness, and physical functioning in a phase 3, double-blind, multicenter study (CL303, NCT02526160). In this trial, subjects were randomized 1:1 to receive burosumab or placebo subcutaneously every 4 weeks. At Week 24, subjects in the placebo group crossed over to receive burosumab (total duration ≥96 weeks). Here, we report final long-term safety results from this trial. Most (119/134, 89%) subjects completed 96 weeks and received 1 mg/kg burosumab; protocol-specified dose reductions were required for 11/134 (8.2%) subjects to effectively manage hyperphosphatemia (all mild [Grade 1]). Mean (±SE) baseline serum phosphorus was 1.98 (±0.03) mg/dL and was 2.97 (±0.05) mg/dL at Week 94 (midpoint of dose interval). Mean (±SE) iPTH level was 96 (±3.8) pg/mL at baseline and progressively declined to 79 (±3.3) pg/mL at Week 96. Nephrocalcinosis score at Week 96 changed by 0 in 101 subjects, -1 in 9 subjects, +1 in 10 subjects (14 subjects not available). There were no meaningful changes in ectopic mineralization. There were no neutralizing antibodies. No treatment-emergent adverse events led to study or treatment withdrawal. Serum phosphorus was maintained with long-term burosumab treatment, with no evidence of loss of effect in adults with XLH. Burosumab dose reductions effectively managed mild hyperphosphatemia. Frequency, severity, and types of AEs reported were consistent with previous burosumab trials.