Burosumab

Last updated

Burosumab
Monoclonal antibody
Type Whole antibody
Source Human
Target FGF 23
Clinical data
Pronunciationbur OH sue mab
Trade names Crysvita
Other namesKRN-23, KRN23, burosumab-twza
AHFS/Drugs.com Monograph
MedlinePlus a618034
License data
Pregnancy
category
Routes of
administration 		Subcutaneous
ATC code
Legal status
Legal status
Pharmacokinetic data
Elimination half-life 16.4 days [10]
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
Formula C6388H9904N1700O2006S46
Molar mass 144090.15 g·mol−1

Burosumab, sold under the brand name Crysvita, is a human monoclonal antibody medication approved 2018 for the treatment of X-linked hypophosphatemia and tumor-induced osteomalacia. [8] [11] [12]

Contents

Medical uses

In the European Union and the United States, burosumab is indicated for the treatment of adults and children ages one year and older with X-linked hypophosphatemia (XLH), a rare, inherited form of rickets. [13] caused by overproduction of a hormone called FGF23 (fibroblast growth factor 23) in bone cells. FGF23 is responsible for blocking phosphate re-absorption in the kidney and the suppression of the vitamin D dependent phosphate absorption in the intestine. Due to the excess activity of FGF23, phosphate levels in the blood are abnormally low (hypophosphatemia), which affects the constitution of bone. [14]

In the United States, burosumab is also approved to treat people age two and older with tumor-induced osteomalacia (TIO), a rare disease which is characterized by the development of tumors causing weakened and softened bones. [15] The tumors associated with TIO release fibroblast growth factor 23 (FGF23) which lowers phosphate levels. [15]

Adverse effects

In trials, injection site reactions were very common, occurring in 52–58% of patients; they were generally mild in severity, and resolved on their own in 1–3 days. [16]

It was approved for use in the European Union in February 2018 to treat children one year of age and older and adolescents with growing skeletons who have X-linked hypophosphataemia with radiographic evidence of bone disease . [17]

In April 2018, the U.S. Food and Drug Administration (FDA) approved burosumab for its intended purpose in patients aged one year and older. [13] The FDA approval fell under both the breakthrough therapy and orphan drug designations. [13] [18] The FDA considered it to be a first-in-class medication. [19]

In 2018, the National Institute for Health and Care Excellence in England and Wales raised concerns regarding the incremental cost-effectiveness of the new treatment [20] but as of 2019 the drug was available through a simple discount scheme. [21]

History

This drug was developed by Ultragenyx and is in a collaborative license agreement with Kyowa Hakko Kirin. [22]

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<span class="mw-page-title-main">Fibroblast growth factor 23</span> Protein found in humans

Fibroblast growth factor 23 (FGF-23) is a protein and member of the fibroblast growth factor (FGF) family which participates in the regulation of phosphate in plasma and vitamin D metabolism. In humans it is encoded by the FGF23 gene. FGF-23 decreases reabsorption of phosphate in the kidney. Mutations in FGF23 can lead to its increased activity, resulting in autosomal dominant hypophosphatemic rickets.

<span class="mw-page-title-main">X-linked hypophosphatemia</span> X-linked dominant disorder that causes rickets

X-linked hypophosphatemia (XLH) is an X-linked dominant form of rickets that differs from most cases of dietary deficiency rickets in that vitamin D supplementation does not cure it. It can cause bone deformity including short stature and genu varum (bow-leggedness). It is associated with a mutation in the PHEX gene sequence (Xp.22) and subsequent inactivity of the PHEX protein. PHEX mutations lead to an elevated circulating (systemic) level of the hormone FGF23 which results in renal phosphate wasting, and local elevations of the mineralization/calcification-inhibiting protein osteopontin in the extracellular matrix of bones and teeth. An inactivating mutation in the PHEX gene results in an increase in systemic circulating FGF23, and a decrease in the enzymatic activity of the PHEX enzyme which normally removes (degrades) mineralization-inhibiting osteopontin protein; in XLH, the decreased PHEX enzyme activity leads to an accumulation of inhibitory osteopontin locally in bones and teeth to block mineralization which, along with renal phosphate wasting, both cause osteomalacia and odontomalacia.

Oncogenic osteomalacia, also known as tumor-induced osteomalacia or oncogenic hypophosphatemic osteomalacia, is an uncommon disorder resulting in increased renal phosphate excretion, hypophosphatemia and osteomalacia. It may be caused by a phosphaturic mesenchymal tumor. Symptoms typically include crushing fatigue, severe muscle weakness and brain fog due to the low circulating levels of serum phosphate.

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Phosphate diabetes is a rare, congenital, hereditary disorder associated with inadequate tubular reabsorption that affects the way the body processes and absorbs phosphate. Also named as X-linked dominant hypophosphatemic rickets (XLH), this disease is caused by a mutation in the X-linked PHEX gene, which encodes for a protein that regulates phosphate levels in the human body. phosphate is an essential mineral which plays a significant role in the formation and maintenance of bones and teeth, energy production and other important cellular processes. phosphate diabetes is a condition that falls under the category of tubulopathies, which refers to the pathologies of the renal tubules. The mutated PHEX gene causes pathological elevations in fibroblast growth factor 23 (FGF23), a hormone that regulates phosphate homeostasis by decreasing the reabsorption of phosphate in the kidneys.

References

  1. 1 2 "Crysvita". Therapeutic Goods Administration (TGA). 17 September 2021. Retrieved 17 September 2021.
  2. ↑ "Updates to the Prescribing Medicines in Pregnancy database". Therapeutic Goods Administration (TGA). 12 May 2022. Retrieved 13 May 2022.
  3. ↑ "Crysvita burosumab 10 mg/mL solution for injection in a 5 mL vial". Therapeutic Goods Administration (TGA). Archived from the original on 17 September 2021. Retrieved 17 September 2021.
  4. ↑ "Crysvita burosumab 10 mg/mL solution for injection in a 5 mL vial". Therapeutic Goods Administration (TGA). Archived from the original (PDF) on 17 September 2021. Retrieved 17 September 2021.
  5. ↑ "Crysvita Product information". Health Canada. 25 April 2012. Retrieved 29 May 2022.
  6. ↑ "Summary Basis of Decision (SBD) for Crysvita". Health Canada . 23 October 2014. Retrieved 29 May 2022.
  7. ↑ "Crysvita 10 mg solution for injection - Summary of Product Characteristics (SmPC)". (emc). 20 April 2020. Retrieved 19 June 2020.
  8. 1 2 "Crysvita- burosumab injection". DailyMed. Retrieved 17 September 2021.
  9. ↑ "Drug Approval Package: Crysvita (burosumab-twza)". U.S. Food and Drug Administration (FDA). 15 May 2018. Retrieved 28 February 2020.
  10. ↑ Zhang X, Imel EA, Ruppe MD, Weber TJ, Klausner MA, Ito T, et al. (February 2016). "Pharmacokinetics and pharmacodynamics of a human monoclonal anti-FGF23 antibody (KRN23) in the first multiple ascending-dose trial treating adults with X-linked hypophosphatemia". Journal of Clinical Pharmacology. 56 (2): 176–85. doi:10.1002/jcph.570. PMC   5042055 . PMID   26073451.
  11. ↑ World Health Organization (2017). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 77". WHO Drug Information. 31 (1). hdl: 10665/330984 .
  12. ↑ "Burosumab (KRN23) for X-Linked Hypophosphatemia (XLH)" (PDF). n.d. Archived from the original (PDF) on 18 April 2018. Retrieved 18 April 2018.
  13. 1 2 3 "FDA approves first therapy for rare inherited form of rickets, x-linked hypophosphatemia" (Press release). U.S. Food and Drug Administration (FDA). 17 April 2018.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  14. ↑ "What Is X-Linked Hypophosphatemia?". Ultragenyx Pharmaceutical. Archived from the original on 23 June 2021. Retrieved 22 February 2020.
  15. 1 2 "FDA Approves First Therapy for Rare Disease that Causes Low Phosphate Blood Levels, Bone Softening". U.S. Food and Drug Administration (Press release). 18 June 2020. Retrieved 19 June 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  16. ↑ FDA Professional Drug Information
  17. ↑ "Crysvita EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 1 March 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  18. ↑ "Crysvita Orphan Drug Designation". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 27 February 2020.
  19. ↑ New Drug Therapy Approvals 2018 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2019. Retrieved 16 September 2020.
  20. ↑ "U.K. cost watchdogs turn away rare disease med Crysvita". Fierce Pharma. 15 June 2018.
  21. ↑ "1 Recommendations | Burosumab for treating X-linked hypophosphataemia in children and young people. Guidance NICE". www.nice.org.uk. Retrieved 14 June 2019.
  22. ↑ "Collaboration with Ultragenyx to Develop and Commercialize KRN23 for X-linked Hypophosphatemia" (Press release). Kyowa Kirin. 4 September 2013. Retrieved 17 April 2018.
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