Objectives: X-linked hypophosphatemia (XLH) is a rare inherited form of osteomalacia characterised by low blood phosphate levels which lead to inadequate mineralisation of bone resulting in rickets, skeletal abnormalities, physical impairment, weakness, and pain. 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 following the first 6 months of burosumab treatment.
Methods: An early access program (EAP) for burosumab was made available for children in the UK 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 conventional treatment. EAP enrolment was between January and March 2018. 135 of 142 applications were approved. 132 have commenced treatment (dose in accordance with EMA marketing authorisation), of whom 31 have completed a median of 24 weeks (2226 weeks) of treatment.
Results: Mean age enrolled was 7.2 years (range 1.614.7), 68% female and 32% male. Mean height and weight at week 0 was 114.9 cm (75157.9 cm) and 27.1 kg (10.567.5 kg) respectively. Mean dose administered was 0.51 mg/kg (0.280.95 mg/kg) at week 0 and 0.89 mg/kg (0.252.01 mg/kg) at week 24 (2226 weeks). Mean fasting serum phosphorus was 0.73 mmol/l (0.50.91 mmol/l) in week 0 rising to 1.06 mmol/l (0.771.48 mmol/l) at week 24 (2226 weeks) representing a 45% increase in serum phosphate. Mean serum ALP fell from 591.5 IU/l (2614089 IU/l) at week 0 to 353.2 IU/l (190733 IU/l) at week 24 (2226 weeks), representing 40% decrease in ALP. No patients discontinued treatment due to adverse events.
Conclusions: Early data from treating children and young people with XLH with burosumab in a real-world UK setting demonstrate that key biochemical responses are aligned with the clinical research program findings. Ongoing monitoring and research is required to confirm the biochemical response translates to the expected subsequent impact on skeletal and non-skeletal outcomes, including linear growth and deformities.
27 - 29 Nov 2019
British Society for Paediatric Endocrinology and Diabetes