ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 66 OC4.2 | DOI: 10.1530/endoabs.66.OC4.2

Burosumab initiation in a UK XLH cohort: real-world use resonates with research evidence

Poonam Dharmaraj1, Christine Burren2, Moira Cheung3, Raja Padidela4, Zulf Mughal4, Nick Shaw5, Vrinda Saraff5, Ruchi Nadar5, Talat Mushtaq6, Renuka Ramakrishnan1, Senith Senniappan1, Sophia Sakha3, John Barton2, Ian Tucker2, Lauren Rayner4, Paul Arundel7, Robyn Gilbey-Cross3, Alexander Tothill8, James Philip9, Nadine Sawoky9, Paul Connor9 & Leigh Mathieson9

1Alder Hey Children’s Hospital, Liverpool, UK; 2Bristol Royal Hospital for Children, Bristol, UK; 3Evelina Children’s Hospital, London, UK; 4Royal Manchester Children’s Hospital, Manchester, UK; 5Birmingham Children’s Hospital, Birmingham, UK; 6Leeds Teaching Hospitals, Leeds, UK; 7Sheffield Children’s Foundation Trust, Sheffield, UK; 8MAP BioPharma, Cambridge, UK; 9Kyowa Kirin International, Galashiels, UK

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 (22–26 weeks) of treatment.

Results: Mean age enrolled was 7.2 years (range 1.6–14.7), 68% female and 32% male. Mean height and weight at week 0 was 114.9 cm (75–157.9 cm) and 27.1 kg (10.5–67.5 kg) respectively. Mean dose administered was 0.51 mg/kg (0.28–0.95 mg/kg) at week 0 and 0.89 mg/kg (0.25–2.01 mg/kg) at week 24 (22–26 weeks). Mean fasting serum phosphorus was 0.73 mmol/l (0.5–0.91 mmol/l) in week 0 rising to 1.06 mmol/l (0.77–1.48 mmol/l) at week 24 (22–26 weeks) representing a 45% increase in serum phosphate. Mean serum ALP fell from 591.5 IU/l (261–4089 IU/l) at week 0 to 353.2 IU/l (190–733 IU/l) at week 24 (22–26 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.

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