Real-world non-interventional post-authorization safety study of long-term use of burosumab in children and adolescents with X-linked hypophosphatemia: first interim analysis

Annemieke M Boot; Gema Ariceta; Signe Sparre Beck-Nielsen; Maria Luisa Brandi; Karine Briot; Carmen de Lucas Collantes; Sandro Giannini; Dieter Haffner; Richard Keen; Elena Levtchenko; M Zulf Mughal; Outi Makitie; Ola Nilsson; Dirk Schnabel; Liana Tripto-Shkolnik; M Carola Zillikens; Jonathan Liu; Alina Tudor; Francesco Emma

doi:10.1177/20406223241247643

Real-world non-interventional post-authorization safety study of long-term use of burosumab in children and adolescents with X-linked hypophosphatemia: first interim analysis

Ther Adv Chronic Dis. 2024 May 18:15:20406223241247643. doi: 10.1177/20406223241247643. eCollection 2024.

Authors

Annemieke M Boot¹, Gema Ariceta², Signe Sparre Beck-Nielsen^{3

4}, Maria Luisa Brandi⁵, Karine Briot⁶, Carmen de Lucas Collantes⁷, Sandro Giannini⁸, Dieter Haffner⁹, Richard Keen¹⁰, Elena Levtchenko¹¹, M Zulf Mughal^{12

13}, Outi Makitie¹⁴, Ola Nilsson^{15

16}, Dirk Schnabel¹⁷, Liana Tripto-Shkolnik^{18

19}, M Carola Zillikens²⁰, Jonathan Liu²¹, Alina Tudor²¹, Francesco Emma²²

Affiliations

¹ Department of Pediatric Endocrinology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen 9713 GZ, The Netherlands.
² Department of Pediatric Nephrology, University Hospital Vall d'Hebron, Autonomous University of Barcelona, Barcelona, Spain.
³ Centre for Rare Diseases, Pediatric Department, Aarhus University Hospital, Aarhus, Denmark.
⁴ Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
⁵ FIRMO Foundation, Florence, Italy.
⁶ AP-HP, Department of Rheumatology, Cochin Hospital, Paris, France.
⁷ Pediatric Nephrology, Hospital Infantil Universitario Niño Jesús, Universidad Autónoma de Madrid, Madrid, Spain.
⁸ Department of Medicine, Clinica Medica 1, University of Padova, Padova, Italy.
⁹ Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany.
¹⁰ Royal National Orthopaedic Hospital, Stanmore, UK.
¹¹ Department of Pediatric Nephrology, Amsterdam University Medical Centre, Amsterdam, The Netherlands.
¹² Department of Pediatric Endocrinology, Royal Manchester Children's Hospital, Manchester, UK.
¹³ Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
¹⁴ Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
¹⁵ Division of Pediatric Endocrinology, Center for Molecular Medicine, Department of Women's and Children's Health, Karolinska Institutet and University Hospital, Stockholm, Sweden.
¹⁶ Department of Pediatrics and School of Medical Sciences, Örebro University and University Hospital, Örebro, Sweden.
¹⁷ Center for Chronically Sick Children, Pediatric Endocrinology, Charitè, University Medicine, Berlin, Germany.
¹⁸ The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
¹⁹ Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center, Tel HaShomer, Israel.
²⁰ Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
²¹ Kyowa Kirin International, Marlow, UK.
²² Division of Nephrology, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.

Abstract

Background: X-linked hypophosphatemia (XLH) is a rare, progressive disorder characterized by excess fibroblast growth factor 23 (FGF23), causing renal phosphate-wasting and impaired active vitamin D synthesis. Burosumab is a recombinant human monoclonal antibody that inhibits FGF23, restoring patient serum phosphate levels. Safety data on long-term burosumab treatment are currently limited.

Objectives: This post-authorization safety study (PASS) aims to monitor long-term safety outcomes in children and adolescents (1-17 years) treated with burosumab for XLH. This first interim analysis reports the initial PASS safety outcomes.

Design: A 10-year retrospective and prospective cohort study.

Methods: This PASS utilizes International XLH Registry (NCT03193476) data, which includes standard diagnostic and monitoring practice data at participating European centers.

Results: At data cut-off (13 May 2021), 647 participants were included in the International XLH Registry; 367 were receiving burosumab, of which 67 provided consent to be included in the PASS. Mean (SD) follow-up time was 2.2 (1.0) years. Mean (SD) age was 7.3 (4.3) years (range 1.0-17.5 years). Mean duration of burosumab exposure was 29.7 (25.0) months. Overall, 25/67 participants (37.3%) experienced ⩾1 adverse event (AE) during follow-up; 83 AEs were reported. There were no deaths, no AEs leading to treatment withdrawal, nor serious AEs related to treatment. The most frequently reported AEs were classified as 'musculoskeletal and connective tissue disorders', with 'pain in extremity' most frequently reported, followed by 'infections and infestations', with 'tooth abscess' the most frequently reported.

Conclusion: In this first interim analysis of the PASS, covering the initial 2 years of data collection, the safety profile of burosumab is consistent with previously reported safety data. The PASS will provide long-term safety data over its 10-year duration for healthcare providers and participants with XLH that contribute to improvements in the knowledge of burosumab safety.

Trial registration: European Union electronic Register of Post-Authorisation Studies: EUPAS32190.

Keywords: X-linked hypophosphatemia; burosumab; patient registry; post-authorization safety study; safety.