SUN-524 Burosumab Initiation In A UK XLH Cohort: Real-World Use Resonates With Research Evidence

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:rickets leading in turn to a spectrum of 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. Real world evidence has an important role in validating the findings of clinical research studies; more data on dose regimen and relevant biochemical outcomes outside of the clinical research study environment is required. We report these criteria following the first three months of burosumab treatment in a real-world setting. 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, confirmed 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.(1) Of the 7 declined, 4 failed to meet diagnostic criteria and 3 had insufficient radiological evidence.(1) 132 have commenced treatment (dose in accordance with EMA marketing authorisation), of whom 41 have completed the initial 12-week burosumab titration period. Results The mean age enrolled was 7.2 years (range <1.6-16.7), 45% female, 43% male and 12% unspecified. The mean height and weight at week 0 was 110.45 cm (75-153 cm) and 25.36 kg respectively. The mean dose administered was 0.57 mg/kg at week 0 and 0.94 mg/kg at week 12 (end of the initial titration period). Mean serum phosphorus was 0.66 mmol/L (0.35-0.85 mmol/L) in week 0 rising to 1.00 mmol/L (0.57-1.58 mmol/L) at week 12 representing a 51.5% increase in serum phosphate. Mean serum ALP fell from 635.48 IU/L (269-2124 IU/L) at week 0 to 522.42 IU/L (190-1473 IU/L) at week 12, representing 18% decrease in ALP. No patients discontinued treatment due to adverse events.(1)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 in line 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. References 1. Kyowa Kirin - data on file