ESPE Yearbook of Paediatric Endocrinology

In brief: This report describes the efficacy and safety of burosumab during the open-label extension period of the original Phase 3 study (weeks 64-88) in 21 children with X-linked hypophosphatemia (XLH) who continued to receive burosumab or crossed over from conventional therapy to burosumab.

Commentary: X-linked hypophosphatemia (XLH) is a rare inherited disorder of phosphorus metabolism caused by loss-of-function mutations in the PHEX gene, resulting in excessive plasma levels of a phosphate-wasting hormone called FGF23. Increased circulating FGF23 inhibits renal phosphate reabsorption and 1,25-dihydroxyvitamin D synthesis, resulting in rickets and osteomalacia, manifested mainly by short stature, bowing of the legs, gait abnormalities and impaired physical function.

Traditionally, XLH has been treated with multiple daily doses of phosphate and an active form of vitamin D. Burosumab is a novel monoclonal antibody to FGF23 approved for the treatment of XLH. In an original randomised, open-label phase 3 study in 61 children aged 1-12 years with XLH previously treated with conventional therapy, switching to burosumab every 2 weeks for 64 weeks restored normal phosphate levels, cured rickets and improved growth and leg bowing compared to conventional therapy. In the current open-label extension phase (weeks 64-88), 21 children originally treated with burosumab or conventional therapy for 64 weeks were followed up to 88 weeks. Children who remained on burosumab continued to show improvements in rickets from baseline between weeks 64 and 88. Children who crossed over from conventional therapy to burosumab showed rapid improvement in phosphate metabolism and improved rickets resolution, confirming the findings of the 64-week pivotal trial. As in the original 64-week study, burosumab was well tolerated in children who continued burosumab for 88 weeks and in those who crossed over from conventional therapy.

These data provide additional support for the use of burosumab in the treatment of paediatric XLH.