Burosumab versus conventional therapy in children with X-linked hypophosphatemia: results of the open-label, phase 3 extension period

In a randomized, open-label phase 3 study of 61 children 1–12 years old with X-linked hypophosphatemia (XLH) previously treated with conventional therapy, changing to bi-weekly (Q2W) burosumab for 64 weeks improved phosphate metabolism, radiographic rickets, and growth compared with conventional therapy. In this open-label extension period (weeks 64–88), 21 children continued burosumab Q2W at the previous dose or crossed over from conventional therapy to burosumab starting at 0.8 mg/kg Q2W and had continued clinical radiographic assessments through week 88. Efficacy endpoints and safety observations were summarized descriptively for the treatment groups (burosumab continuation, n = 6; crossover, n = 15). At week 88 compared with baseline, improvements in the following outcomes were observed in the burosumab continuation and crossover groups, respectively: mean (SD) RGI-C rickets total score (primary outcome), +2.11 (0.27) and + 1.89 (0.35); mean (SD) RGI-C lower limb deformity score, +1.61 (0.91) and + 0.73 (0.82), and mean (SD) height Z-score + 0.41 (0.50) and + 0.08 (0.34). Phosphate metabolism normalized rapidly in the crossover group and persisted in the continuation group. Mean (SD) serum ALP decreased from 169% (43%) of the upper limit of normal (ULN) at baseline to 126% (51%) at week 88 in the continuation group, and from 157% (33%) of the ULN at baseline to 111% (23%) at week 88 in the crossover group. During the extension period, treatment-emergent adverse events (AEs) were reported in all six children in the burosumab continuation group and in 14/15 children in the cross-over group. AE profiles in the randomized and extension periods were similar, with no new safety signals identified. Thus, improvements from baseline in radiographic rickets continued in the extension period among children with XLH who remained on burosumab. Children who crossed over from conventional therapy to burosumab demonstrated rapid improvement in phosphate metabolism and improved rickets healing over the ensuing 22 weeks.