Objectives: X-linked hypophosphatemia (XLH) is a rare inherited form of osteomalacia characterised by low blood phosphate levels which lead to inadequate mineralization of bone and rickets. Burosumab is an anti-FGF23 fully human monoclonal-antibody, and the first treatment to target the underlying pathophysiology of XLH. We report relevant real-world biochemical data on children under five years old for the first 6 months of treatment.
Methods: An early access program (EAP) for burosumab was made available for children in the United Kingdom with XLH in 12 specialist centres. Inclusion criteria for the EAP included radiographic evidence of disease, XLH confirmed by genetic PHEX mutation or familial X-linked inheritance mutation or family history. Patients must have also had an unsatisfactory response to best available care and treatment. EAP enrolment was between January and March 2018. A total of 142 applications were received of which 135 were approved with 132 receiving treatment (dose in accordance with EMA marketing authorisation).
Results: Data are available on 10 children under five years (mean age 2.8 years; 1.64 years) who have completed a median of 6 months (2026 weeks) of burosumab treatment. Mean height and weight at week 0 was 85.5 cm (7597.3 cm) and 12.8 kg (9.918.2 kg) respectively. Mean dose administered was 0.81 mg/kg (0.551.01 mg/kg) at week 0 and 1.09 mg/kg (0.572.01 mg/kg) at the end of the 2026 week period. Mean fasting serum phosphorus was 0.73 mmol/l (0.60.83 mmol/l) in week 0 rising to 1.02 mmol/l (0.821.3 mmol/l) at week 2026 representing a 40% increase in serum phosphate levels. Mean serum ALP fell from 808.2 IU/l (2972124 IU/l) at week 0 to 612 IU/l (2911459 IU/l) at week 2026, representing a 24% decrease in ALP. No patients discontinued treatment due to adverse events.
Conclusions: Early data from treating young children with XLH with burosumab in a real-world UK setting demonstrate that key biochemical responses are aligned with findings from the clinical study program. This provides reassurance that the improvement in key biochemical parameters is consistent across all ages within its licensed indication.
27 - 29 Nov 2019
British Society for Paediatric Endocrinology and Diabetes