Revolutionizing the Treatment of Children with XLH
Sprache des Vortragstitels:
European Society of Paediatric Endocrinology, 57th Annual Meeting
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In X-linked hypophosphatemia (XLH), elevated secretion of fibroblast growth factor 23 (FGF23) causes hypophosphatemia and consequently rickets, osteomalacia, and skeletal deformities. Burosumab, a monoclonal antibody against FGF23, is under investigation for XLH.
In an open-label, Phase 2 study, 52 children with XLH were randomized 1:1 to receive subcutaneous burosumab every two (Q2W) or four (Q4W) weeks titrated to achieve low-normal serum phosphorus levels to identify optimal dose and regimen. The primary endpoint was change from baseline in radiographic rickets at week 40 and 64. Additional endpoints were pharmacodynamic markers, growth, physical ability, patient-reported outcomes, and adverse events (AEs).
At week 40, mean Total Rickets Severity Score improved by 61% with Q2W and 37% with Q4W dosing (both p<0.001) and improvements were sustained at Week 64. Mean serum phosphorus increased after the first dose of burosumab and over half of subjects attained levels within the normal range (3.2-6.1 mg/dL; 1.03-1.97 mmol/L) by week 6. Q2W dosing maintained steady serum phosphorus levels through week 64. Mean dose (mg/kg) at week 40 was 0.98 and 1.50 with Q2W and Q4W, respectively. Mean serum alkaline phosphatase decreased by 20% overall at week 64. Mean standing height z-score increased overall, with the greatest improvements with Q2W dosing (Week 64 +0.19; p<0.001). Physical ability and pain improved. Burosumab showed an acceptable safety profile; most AEs were mild to moderate in severity.
In children with XLH, burosumab improved renal phosphate reabsorption, serum phosphorus levels, rickets severity, growth, pain, and physical function.
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