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, re...

In brief: This article reviews the evidence and provides expert opinion on the safe and appropriate use of denosumab in children and adolescents with RANKL-mediated disorders such as giant cell bone tumours, fibrous dysplasia and juvenile Paget’s disease.Commentary: Receptor activator of nuclear factor κB ligand (RANKL) is expressed by osteogenic cells and induces osteoclast differentiation by binding to RANK on osteoclast precursors. Excessive...

In brief: This 1-year, open-label, randomised controlled trial examined the effects and tolerability of denosumab, compared with zoledronic acid, on bone mineral density (BMD), spinal morphometry, and safety in a large cohort of children (n=84) with osteogenesis imperfecta. Treatment with denosumab increased BMD and improved spinal morphometry in children with OI, but was frequently associated with rebound hypercalcaemia (in 31%). This rebound hypercalcaemia could be alleviate...

In brief: This multinational, randomised, double-blind, placebo-controlled, Phase 2 study examined the safety and efficacy of vosoritide, a recombinant C-type natriuretic peptide (CNP) analogue, in 75 children with achondroplasia under age 5 years. Mean gain in height Z-score after 52-weeks was 0•25 (95% CI -0•02 to 0•53). The study was sponsored by BioMarin Pharmaceutical.Commentary: Achondroplasia is one of the most common constitutional...

In brief: This single-arm, open-label, single-centre, Phase 2 study in the US examined the safety and efficacy of vosoritide, a recombinant C-type natriuretic peptide (CNP) analogue, in 26 children with hypochondroplasia. Height SDS increased by (mean) 0.36 during the 12-month treatment period versus the observation period. The study was sponsored by BioMarin Pharmaceutical.Commentary: Hypochondroplasia is a rare skeletal dysplasia that manifests mainly ...

In brief: This multinational, randomised, double-blind, placebo-controlled, dose-escalation Phase 2 study evaluated the safety and efficacy of TransCon CNP (navepegritide), a C-type natriuretic peptide (CNP) analogue designed to allow continuous CNP exposure with once-weekly dosing, in 42 children with achondroplasia aged 2-10 years. The study was sponsored by Ascendis Pharma.Commentary: Achondroplasia is one of the most common constitutional bone disord...

In brief: This study investigated the effect of infigratinib, a selective and orally bioavailable FGFR1-3 inhibitor, administered at different doses or according to different dosing regimens, on bone growth in a mouse model mimicking achondroplasia (Fgfr3Y367C/+). This study was partially sponsored by a grant from BridgeBio/QED Therapeutics.Commentary: Achondroplasia is one of the most common constitutional bone diseases (> 300,000 affecte...