Burosumab vs 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 aged 1-12 years old with X-linked hypophosphatemia (XLH) previously treated with conventional therapy, changing to burosumab every 2 weeks (Q2W) for 64 weeks improved the 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 with continued clinical radiographic assessments through week 88. Efficacy endpoints and safety observations were summarized descriptively for both 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 alkaline phosphatase 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 6 children in the burosumab continuation group and 14/15 children in the crossover group. The AE profiles in the randomized and extension periods were similar, with no new safety signals identified. 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 a rapid improvement in phosphate metabolism and improved rickets healing over the ensuing 22 weeks.
Competing Interests: L.M.W. has been a consultant to Ultragenyx and Kyowa Kirin and participated in clinical trials with Ultragenyx Pharmaceutical Inc., with funds to Dr Ward’s institution. W.H. served as an investigator in clinical trials with, and as a consultant for, Ultragenyx Pharmaceutical Inc. and serves as a clinical investigator in clinical trials with, and has received research funding from, Kyowa Kirin. F.H.G. has been a consultant to, and participated in clinical trials with, Ultragenyx Pharmaceutical Inc. and Kyowa Kirin. A.A.P. has been a consultant to, and served as an investigator in clinical trials with, Ultragenyx Pharmaceutical Inc. M.P.W. has lectured for Ultragenyx Pharmaceutical Inc. C.F.M. is a consultant for Kyowa Kirin and has received research funding from Kyowa Kirin. O.N. has received speakers’ honoraria from Kyowa Kirin, Abbott, and BioMarin, consulting fees from Kyowa Kirin and BioMarin, and research support from Kyowa Kirin. J.H.S. has received institutional research funding from and personal honoraria for participation in an advisory board from Ultragenyx Pharmaceutical Inc. R.P. has no conflicts to disclose. N.N. has been a consultant to, and participated in clinical trials with, Kyowa Kirin. H.I.C. has been a consultant to, and participated in clinical trials with, Ultragenyx Pharmaceutical Inc. H.T. has received research funding from Kyowa Kirin co. Ltd. P.P. has been an employee of Lumos Pharma Inc. and owns stock in Lumos Pharma Inc. and Ascendis Pharma. G.S.G. has been a consultant for Ultragenyx Pharmaceutical Inc. A.C. and J.L.M. are employees of and own stock in Ultragenyx Pharmaceutical Inc. E.A.I. has been a consultant to, and participated in clinical trials with, Ultragenyx Pharmaceutical Inc. E.S., K.M., A.B., and F.P. report no conflicts.
(© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)