SUN-736 Non-interventional Post-authorisation Safety Study Of Burosumab In The Treatment Of Adults With X-linked Hypophosphataemia: First Interim Analysis

Abstract Disclosure: G. Ariceta: Advicenne, Alexion, Alnylam, Chiesi, Kyowa Kirin, Recordati Rare Diseases. S. Beck-Nielsen: Inozyme, Kyowa Kirin. A. Boot: Kyowa Kirin, Ultragenyx. M. Brandi: Amgen, Ascendis, Bruno Farmaceutici, Calcilytix, Kyowa Kirin, Alexion, Amgen, Amolyt, CoGeDi, Echolight, Gedeon Richter, Monte Rosa Therapeutics, UCB, Aboca, Enterabio, Personal Genomics, Septerna. K. Briot: Amgen, Kyowa Kirin, Theramex,, UCB. C. Collantes: Alexion, Chiesi, Kyowa Kirin. F. Emma: Avrobio, Chiesi, Kyowa Kirin, Otsuka, Recordati Rare Diseases.. S. Giannini: None. D. Haffner: Biologix, Chiesi, Kyowa Kirin, Ultragenyx. R. Keen: Kyowa Kirin. E. Levtchenko: Advicenne, Chiesi, Kyowa Kirin, Novartis, Recordati. O. Nilsson: BioMarin, Kyowa Kirin. O. Mäkitie: BridgeBio, Kyowa Kirin, Ultragenyx. M. Mughal: Inozyme Pharma, Ipsen, Kyowa Kirin. D. Schnabel: BioMarin, Kyowa Kirin, Novo Nordisk, Sandoz. L. Tripto-Shkolnik: Amgen, Kyowa Kirin. M.C. Zillikens: Amgen, Kyowa Kirin. E. Benchekroun: Kyowa Kirin. E. Eltahan: Kyowa Kirin. M. Melogno-Klinkas: Kyowa Kirin. P. Joos-Vandewalle: Kyowa Kirin. Aims/Purpose Burosumab, a fully human anti-FGF23 antibody, is approved for treating X-linked hypophosphataemia (XLH), a rare, genetic, progressive disease. As part of the burosumab risk management plan, a post-authorisation safety study (PASS) was initiated, utilizing International XLH Registry (NCT03193476) data. Methods The PASS is a 10-year multi-centre, non-interventional, observational study. Primary objectives assessed burosumab safety outcomes in adults with XLH, including long term safety, outcomes in pregnancy and participants with mild to moderate chronic kidney disease (CKD) at baseline. Secondary objective compared burosumab and oral phosphate and/or active vitamin D (Pi/VitD) safety. Results By 18 June 2024, 67 enrolees received burosumab (BUR+) and 255 received Pi/VitD (Pi/VitD+) only. Adverse event (AE) reporting was solicited in BUR+ and unsolicited in Pi/VitD+. Of BUR+ participants, 44 (65.7%) had any AE; 8 (11.9%) had AEs considered related to burosumab. No AEs led to death or treatment withdrawal. A serious adverse event (SAE), cholecystitis, occurred in 1 (1.5%) participant; no SAEs were related to burosumab. Of Pi/VitD+ participants, 52 (20.4%) had an AE; 8 (3.1%) had AEs considered related to Pi/VitD. AEs led to 1 (0.4%) death, related to cancer, and 2 (0.8%) treatment withdrawals. SAEs occurred in 14 (5.5%) participants; 1 (0.4%) had SAEs related to Pi/VitD. Common AEs in BUR+ were asthenia, pain and arthralgia and in Pi/Vit+ were urinary tract infections, arthralgia and back pain. Pregnancy occurred in 0 BUR+ and 5 (2.0%) Pi/VitD+ participants. Hospitalisation for any reason occurred in 59 (88.1%) BUR+ and 166 (65.1%) Pi/VitD+ participants; 1 (1.5%) BUR+ participant was hospitalised for cholecystitis (unlikely related to burosumab). Increased parathyroid hormone occurred in 3 (4.5%) BUR+, without hypercalcemia, and 2 (0.8%) Pi/VitD+ participants, 1 with hypercalcemia. Ectopic mineralisation occurred in 2 (3.0%) participants in BUR+ (1 unrelated chondrocalcinosis; 1 related nephrolithiasis) and 3 (1.2%) in PiVitD+. No hyperphosphataemia was reported and cardiovascular disease and cancer were rare and not treatment related. For this analysis, CKD outcomes were too limited to interpret. Conclusion The safety profile of burosumab was consistent with previous reports, with no new safety concerns. No deaths, events of hyperphosphataemia or SAE considered related to burosumab were reported. The higher AE rate in BUR+ vs Pi/VitD+ is likely attributed to differences in reporting. Presentation: Sunday, July 13, 2025