Burosumab in X-linked hypophosphatemia: a profile of its use in the USA
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Burosumab (Crysvita®), a fully human IgG1 monoclonal antibody directed at fibroblast growth factor 23 (FGF23), is indicated for the treatment of X-linked hypophosphatemia (XLH), a condition associated with excessive FGF23 production. It directly addresses the excessive FGF23 activity in patients with XLH by binding to FGF23, and inhibiting its signaling. This leads to increased gastrointestinal phosphate absorption and renal phosphate reabsorption, thereby improving serum phosphate levels, and, ultimately, bone mineralization and the risk of bone disease. In clinical trials, subcutaneous burosumab increased serum phosphorus levels in pediatric and adult patients with XLH, as well as significantly improving the severity of rickets in children, and improving pain, stiffness, physical functioning, and fracture/pseudofracture healing in adults. Burosumab is well tolerated by children and adults with XLH, with most treatment-emergent adverse events being of mild to moderate severity.
The manuscript was reviewed by: S. Fukumoto, Department of Molecular Endocrinology, Fujii Memorial Institute of Medical Sciences, Tokushima University, Tokushima, Japan; L.-N. Veilleux, Motion Analysis Center, Shriners Hospital for Children-Canada, Montréal, QC, Canada. During the peer review process, Ultragenyx Pharmaceutical Inc., the marketing-authorization holder of burosumab, was also offered an opportunity to provide a scientific accuracy review of their data. Changes resulting from comments received were made on the basis of scientific and editorial merit.
Compliance with ethical standards
The preparation of this review was not supported by any external funding.
Conflict of interest
K.A. Lyseng-Williamson is an employee of Adis/Springer, is responsible for the article content and declares no conflicts of interest.
- 4.Chesher D, Oddy M, Darbar U, et al. Outcome of adult patients with X-linked hypophosphatemia caused by PHEX gene mutations. J Inherit Metab Dis. 2018;1–12.Google Scholar
- 5.Crysvita® (burosumab-twza) injection for subcutaneous use: US prescribing information. Novato (CA): Ultragenyx Pharmaceutical Inc.; 2018.Google Scholar
- 6.Crysvita (burosumab): summary of product characteristics. London: European Medicines Agency; 2018.Google Scholar
- 9.Portale A, Imel E, Whyte M, et al. Burosumab for X-linked hypophosphatemia (XLH): results from two pediatric phase 2 trials [abstract no. 525]. Endocr Pract. 2018;24(Suppl 1):119–20.Google Scholar
- 10.Zhang X, Peyret T, Gosselin NH, et al. Population pharmacokinetic and pharmacodynamic analyses from a 4-month intradose escalation and its subsequent 12-month dose titration studies for a human monoclonal anti-FGF23 antibody (KRN23) in adults with X-linked hypophosphatemia. J Clin Pharmacol. 2016;56(4):429–38.CrossRefGoogle Scholar
- 12.Ruppe M, Peacock M, Weber T, et al. Clinical and radiographic characteristics of adult X-linked hypophosphatemia (XLH) in a cohort of patients treated with KRN23, an antibody to FGF23 [abstract no. MO0319]. In: 38th annual meeting of the American Society for Bone and Mineral Research. 2016.Google Scholar
- 16.Högler W, Carpenter TO, Imel E, et al. Burosumab, an anti-FGF23 monoclonal antibody, for X-linked hypophosphatemia (XLH): analysis by age from two phase 2 pediatric trials [abstract no. P086]. Calcif Tissue Int. 2018;102(Suppl 1):S37.Google Scholar
- 17.Carpenter T, Imel E, Gottesman GS, et al. KRN23 effects on phosphate and vitamin d metabolism in children < 5 years old with X-linked hypophosphatemia (XLH) [abstract no. FC14]. Horm Res Paediatr. 2017;88(Suppl 1):10–1.Google Scholar
- 19.Kamenicky P, Lachmann R, Carpenter TO, et al. A phase 3 randomized, double-blind, placebo-controlled study investigating the efficacy and safety of burosumab, an anti-FGF23 antibody, in adult X-linked hypophosphatemia [abstract no. OC3.1]. Endocrine Abstracts. 2018;56:64.Google Scholar
- 20.Lachmann R, Kamenicky P, Carpenter TO, et al. A phase 3 randomized, double-blind, placebo-controlled study investigating the efficacy and safety of burosumab, an anti-FGF23 antibody, in adult X-linked hypophosphatemia (XLH) [abstract no. PLO11]. Calcif Tissue Int. 2018;102(Suppl 1):S6–7.Google Scholar