Objective: We constructed height growth curves for children with XLH from birth to early adolescence, a majority of whom received conventional therapy consisting of multiple daily doses of oral phosphate and active vitamin D.
Methods: Growth data from four clinical studies were pooled to construct the growth curves. UX023-CL002 was an observational, retrospective chart review of 103 children with XLH, 114 years of age. Pre-treatment data were collected from three remaining clinical studies (each investigating the safety and efficacy of burosumab, a fully human monoclonal antibody against FGF23): a phase 2 trial (UX023 CL201, NCT02163577) in 52 children with XLH ages 512 years old at enrollment; a phase 2 trial (UX023 CL205, NCT02750618) in 13 children with XLH, 14 years old at enrollment; and a phase 3 trial (UX023-CL301, NCT02915705) in 61 children with XLH, 112 years old at enrollment. We constructed height-for-age growth curves including values for the 5th, 10th, 25th, 50th, 75th, 90th and 95th percentiles for these children with XLH, and compared these data to growth curves representing population norms from the CDC (year 2000).
Results: 228 patients (132 girls, 96 boys) with 2,381 height measurements were included. Nearly all subjects (>99%) had received conventional therapy before enrollment. For boys at 0.25, 0.50, 0.75, 1.0, and 2.0 years-old, the median height percentile was 46%, 37%, 26%, 18%, and 5% respectively; girls median height percentile was 52%, 37%, 25%, 18%, and 7%, respectively. Compared to the CDC growth curves, height velocity in children with XLH fell below that of healthy children near 1 year of age and progressively declined during early childhood, with all median height percentiles <8% between 2 and 12 years-old.
Conclusion: Though nearly all subjects had received conventional therapy, children with XLH show evidence of decreased height velocity by 1 year of age. XLH growth curves provide a helpful point of reference to evaluate therapeutic interventions on growth, and in particular will assist with objective evaluations of novel treatment approaches, such as burosumab. Future research will aim to collect additional growth data from these patients to provide complete XLH growth curves through the adolescent years.
Disclosure: Dr. Carpenter and Whyte served as clinical investigators for studies sponsored by Ultragenyx Pharmaceutical. Dr.s Skrinar, Chen, and San Martin are employees and shareholders of Ultragenyx Pharmaceutical.