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Drugs & Therapy Perspectives

, Volume 34, Issue 11, pp 497–506 | Cite as

Burosumab in X-linked hypophosphatemia: a profile of its use in the USA

  • Katherine A. Lyseng-Williamson
Adis Drug Q&A

Abstract

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.

Notes

Acknowledgements

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

Funding

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.

References

  1. 1.
    Carpenter TO, Imel EA, Holm IA, et al. A clinician’s guide to X-linked hypophosphatemia. J Bone Miner Res. 2011;26(7):1381–8.CrossRefGoogle Scholar
  2. 2.
    Bacon S, Crowley R. Developments in rare bone diseases and mineral disorders. Ther Adv Chronic Dis. 2018;9(1):51–60.CrossRefGoogle Scholar
  3. 3.
    Fukumoto S. Targeting fibroblast growth factor 23 signaling with antibodies and inhibitors, is there a rationale? Front Endocrinol (Lausanne). 2018;9:48.CrossRefGoogle Scholar
  4. 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. 5.
    Crysvita® (burosumab-twza) injection for subcutaneous use: US prescribing information. Novato (CA): Ultragenyx Pharmaceutical Inc.; 2018.Google Scholar
  6. 6.
    Crysvita (burosumab): summary of product characteristics. London: European Medicines Agency; 2018.Google Scholar
  7. 7.
    Carpenter TO, Imel EA, Ruppe MD, et al. Randomized trial of the anti-FGF23 antibody KRN23 in X-linked hypophosphatemia. J Clin Invest. 2014;124(4):1587–97.CrossRefGoogle Scholar
  8. 8.
    Carpenter TO, Whyte MP, Imel EA, et al. Burosumab therapy in children with X-linked hypophosphatemia. N Engl J Med. 2018;378(21):1987–98.CrossRefGoogle Scholar
  9. 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. 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
  11. 11.
    Imel EA, Zhang X, Ruppe MD, et al. Prolonged correction of serum phosphorus in adults with X-linked hypophosphatemia using monthly doses of KRN23. J Clin Endocrinol Metab. 2015;100(7):2565–73.CrossRefGoogle Scholar
  12. 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
  13. 13.
    Insogna KL, Briot K, Imel EA, et al. A randomized, double-blind, placebo-controlled, phase 3 trial evaluating the efficacy of burosumab, an anti-FGF23 antibody, in adults with X-linked hypophosphatemia: week 24 primary analysis. J Bone Miner Res. 2018;33(8):1382–93.CrossRefGoogle Scholar
  14. 14.
    Aono Y, Yamazaki Y, Yasutake J, et al. Therapeutic effects of anti-FGF23 antibodies in hypophosphatemic rickets/osteomalacia. J Bone Miner Res. 2009;24:1879–88.CrossRefGoogle Scholar
  15. 15.
    Zhang X, Imel EA, Ruppe MD, et al. Pharmacokinetics and pharmacodynamics of a human monoclonal anti-FGF23 antibody (KRN23) in the first multiple ascending-dose trial treating adults with X-linked hypophosphatemia. J Clin Pharmacol. 2016;56(2):176–85.CrossRefGoogle Scholar
  16. 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. 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
  18. 18.
    Ruppe MD, Zhang X, Imel EA, et al. Effect of four monthly doses of a human monoclonal anti-FGF23 antibody (KRN23) on quality of life in X-linked hypophosphatemia. Bone Rep. 2016;5:158–62.CrossRefGoogle Scholar
  19. 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. 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

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.SpringerAucklandNew Zealand

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