Second interim analysis of the post-authorisation safety study (PASS) of burosumab in paediatric patients with X-linked hypophosphataemia

Objective: X-linked hypophosphataemia (XLH) is a rare genetic disorder characterised by defective bone and tooth mineralisation. Burosumab is a recombinant, human, anti-fibroblast growth factor 23 monoclonal antibody approved for treating XLH. Due to the rarity of the disease, additional safety data for the treatment of XLH with burosumab are required. Design: A post-authorisation safety study analysis of data for paediatric participants from the International X-linked Hypophosphataemia Registry. This study included standard diagnostic and monitoring clinical data at participating centres, regardless of treatment. Methods: This was a second interim analysis performed 5 years after study initiation in the paediatric population. Primary objectives assessed safety outcomes in children and adolescents with XLH. The secondary objective compared safety outcomes with burosumab vs phosphate and/or active vitamin D. Results: In total, 340 participants were treated with ≥1 dose of burosumab, and 91 were treated with phosphate and/or active vitamin D. Overall, 37.4% and 22.0% of participants in the burosumab or phosphate and/or active vitamin D cohorts, respectively, experienced ≥1 adverse event. The proportions of participants with events were similar among children and adolescents. Forty-nine (14.4%) participants reported events possibly/probably related to burosumab. No events led to the withdrawal of burosumab. In both cohorts, no serious adverse events were considered related to treatment, and there were no deaths. Hospitalisations occurred in ∼71% of participants. Hyperphosphataemia, elevated parathyroid hormone, and ectopic mineralisation events were rare. Conclusions: The safety profile of burosumab was consistent with previous studies, and no new safety concerns were reported for children or adolescents.