Burosumab

Identification

Name
Burosumab
Accession Number
DB14012
Description

Burosumab (KRN23) is an entirely human monoclonal IgG1 antibody that binds excess fibroblast growth factor 23 (FGF23) and has been successfully tested in clinical trials in children with X-linked hypophosphatemic rickets 1.

The U.S. Food and Drug Administration approved Crysvita (burosumab) in April 2018. This is the first drug approved to treat adults and children ages 1 year and older with X-linked hypophosphatemia (XLH), which is a rare, inherited form of rickets. X-linked hypophosphatemia causes low circulating levels of phosphorus in the blood. It causes impaired bone growth and development in children and adolescents and issues with bone mineralization throughout a patient’s life 3.

XLH is a serious disease which affects about 3,000 children and 12,000 adults in the United States. Most children with XLH suffer from bowed or bent legs, short stature, bone pain and severe dental pain. Some adults with this condition suffer from persistent, unrelenting discomfort and complications, such as joint pain, impaired mobility, tooth abscesses and hearing loss 3.

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
C6388H9904N1700O2006S46
Protein Average Weight
144100.0 Da
Sequences
> Burosumab Heavy Chain Sequence
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGIINPISGSTSN
AQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDIVDAFDFWGQGTMVTVSSAST
KGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSV
FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY
RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTK
NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG
NVFSCSVMHEALHNHYTQKSLSLSPGK
> Burosumab Light Chain Sequence
AIQLTQSPSSLSASVGDRVTITCRASQGISSALVWYQQKPGKAPKLLIYDASSLESGVPS
RFSGSGSGTDFTLTISSLQPEDFATYYCQQFNDYFTFGPGTKVDIKRTVAAPSVFIFPPS
DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL
SKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format
Synonyms
  • Burosumab (genetical recombination)
  • burosumab-twza
External IDs
  • KRN-23
  • KRN23

Pharmacology

Indication

This drug is indicated for the treatment of X-linked hypophosphatemia with radiological evidence of bone disease in children of 1 year of age and older and adolescents with growing skeletons 4.

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

This drug has the ability to reduce the loss of phosphate, to improve pathologically low serum phosphate concentrations and other metabolic changes, as well as to reduce the severity of rickets as seen radiographically 5. In summary, this drug works to support of bone mineralization 4.

Mechanism of action

Burosumab is a recombinant human monoclonal antibody (IgG1) that both binds to and inhibits the actions of fibroblast growth factor 23 (FGF23). By inhibiting this growth factor, burosumab increases the tubular reabsorption of phosphate from the kidney and thus increases serum concentration of 1, 25 dihydroxy-Vitamin D 4. This form of vitamin D enhances intestinal absorption of phosphate and calcium, supporting bone mineralization 8.

TargetActionsOrganism
AFibroblast growth factor 23
antagonist
Humans
Absorption

Burosumab absorption after subcutaneous injection sites into to the blood circulation is nearly complete. Following the subcutaneous route of administration, the time to reach maximum serum concentrations (Tmax) of burosumab is estimated at 5-10 days. The peak serum concentration (Cmax) and area under the concentration-time curve (AUC) of serum burosumab is proportional to the dose, over the dose range of 0.1-2.0 mg/kg 4.

Volume of distribution

Burosumab is comprised solely of amino acids and carbohydrates as a native immunoglobulin and is not likeluy to be eliminated by hepatic metabolic mechanisms. The metabolism of burosumab and elimination are expected to follow the immunoglobulin clearance pathways, which results in its degradation to smaller peptides and amino acids 4.

Protein binding
Not Available
Metabolism

Burosumab is composed solely of amino acids and carbohydrates as a native immunoglobulin and is unlikely to be eliminated via hepatic metabolic mechanisms. Its metabolism and elimination are expected to follow the immunoglobulin clearance pathways, resulting in degradation to small peptides and individual amino acids 4.

Route of elimination

Because of its molecular size, burosumab is not likely to be directly excreted 4.

Half-life

About 19 days 4.

Clearance

The clearance of burosumab depends on weight and is estimated to be 0.290 L/day and 0.136 L/day in a typical adult (70 kg) and pediatric (30 kg) XLH patient, respectively 4.

Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

The toxicity of Crysvita can be classified into several categories 4:

Ectopic mineralisation: Clinically manifested by nephrocalcinosis, has been seen in patients with XLH treated with oral phosphorous and vitamin D analogues. These drugs should be stopped at least 1 week before starting burosumab treatment 4.

Monitoring for signs and symptoms of nephrocalcinosis, e.g. by renal ultrasonography, is recommended at the beginning of treatment and at intervals of every 6 months for the first 12 months of treatment, and yearly thereafter. Regular monitoring of plasma alkaline phosphatases, Calcium, PTH, and creatinine is advised at 6 months intervals(every 3 months for children 1- 2 years) or as indicated 4.

Monitoring of urine calcium and phosphate is suggested every 3 months.

Hyperphosphatemia

Fasting serum phosphate level must be followed due to the risk of hyperphosphatemia while taking this drug. To decrease the risk for ectopic mineralization, it is advised that fasting serum phosphate is aimed to be in the lower end of the normal reference range for any given age. Dose interruption and/or dose reduction may be required. Regular measurement of postprandial serum phosphate is advised 4.

Serum parathyroid hormone increases

Increases in serum parathyroid hormone have been measured in some XLH patients while undergoing treatment with burosumab. Regular measurement of serum parathyroid hormone is recommended 4.

Injection site reactions

Administration of burosumab, like other injections, can lead to local injection site reactions. Administration of this drug should cease in any patient experiencing severe injection site reactions and appropriate medical therapy administered 4.

Hypersensitivity

Burosumab should be discontinued if serious hypersensitivity reactions occur and appropriate medical treatment should be provided 4.

Reproductive toxicity/pregnancy

There are no or limited amount of data available from the use of burosumab in pregnant women. Studies in animals have demonstrated reproductive toxicity. Burosumab use is not advised during pregnancy and in women of childbearing potential/age currently not using contraception 4.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Burosumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Burosumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Burosumab.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Burosumab.
Anthrax immune globulin humanThe risk or severity of adverse effects can be increased when Anthrax immune globulin human is combined with Burosumab.
Antilymphocyte immunoglobulin (horse)The risk or severity of adverse effects can be increased when Antilymphocyte immunoglobulin (horse) is combined with Burosumab.
Antithymocyte immunoglobulin (rabbit)The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Burosumab.
Asfotase alfaThe risk or severity of adverse effects can be increased when Asfotase alfa is combined with Burosumab.
AtezolizumabThe risk or severity of adverse effects can be increased when Atezolizumab is combined with Burosumab.
AtoltivimabThe risk or severity of adverse effects can be increased when Burosumab is combined with Atoltivimab.
Additional Data Available
  • Extended Description
    Extended Description
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    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity
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    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level
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    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action
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Food Interactions
Not Available

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CrysvitaSolution10 mgSubcutaneousKyowa Kirin Limited2019-01-28Not applicableCanada flag
CrysvitaInjection10 mg/1mLSubcutaneousUltragenyx Pharmaceutical Inc.2018-04-18Not applicableUS flag
CrysvitaSolution30 mgSubcutaneousKyowa Kirin Limited2019-01-28Not applicableCanada flag
CrysvitaInjection20 mg/1mLSubcutaneousUltragenyx Pharmaceutical Inc.2018-04-18Not applicableUS flag
CrysvitaSolution20 mgSubcutaneousKyowa Kirin Limited2019-01-28Not applicableCanada flag
CrysvitaInjection30 mg/1mLSubcutaneousUltragenyx Pharmaceutical Inc.2018-04-18Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
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    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
M05BX05 — Burosumab
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Chemical Identifiers

UNII
G9WJT6RD29
CAS number
1610833-03-8

References

General References
  1. Kutilek S: Burosumab: A new drug to treat hypophosphatemic rickets. Sudan J Paediatr. 2017;17(2):71-73. doi: 10.24911/SJP.2017.2.11. [PubMed:29545670]
  2. Kinoshita Y, Fukumoto S: X-linked hypophosphatemia and FGF23-related hypophosphatemic diseases -Prospect for new treatment. Endocr Rev. 2018 Jan 26. pii: 4825438. doi: 10.1210/er.2017-00220. [PubMed:29381780]
  3. FDA approves first therapy for rare inherited form of rickets, x-linked hypophosphatemia [Link]
  4. Crysvita Drug Label [Link]
  5. Burosumab for a rare bone disease [Link]
  6. DRUG: Burosumab [Link]
  7. NHS document [Link]
  8. Burosumab for XLH [Link]
KEGG Drug
D10913
RxNav
2043855
Wikipedia
Burosumab
AHFS Codes
  • 40:92.00 — Electrolytic, Caloric and Water Balance Agents, Miscellanous

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentEpidermal Nevus Syndrome (ENS)1
4RecruitingOtherX-linked Hypophosphatemia (XLH)1
4RecruitingTreatmentRare Diseases / X-linked Hypophosphatemia (XLH)1
3Active Not RecruitingTreatmentXLH1
3CompletedTreatmentHypophosphatemia / Hypophosphatemic Rickets / Pain, Chronic1
3CompletedTreatmentX-linked Hypophosphatemia (XLH)3
3CompletedTreatmentX-linked Hypophosphatemic Rickets/Osteomalacia1
3RecruitingTreatmentX-linked Hypophosphatemia (XLH)1
2Active Not RecruitingTreatmentEpidermal Nevus Syndrome (ENS) / Tumor Induced Osteomalacia (TIO)1
2Active Not RecruitingTreatmentTumor-Induced Osteomalacia or Epidermal Nevus Syndrome1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionSubcutaneous10 mg/1mL
InjectionSubcutaneous20 mg/1mL
InjectionSubcutaneous30 mg/1mL
Injection, solutionCutaneous; Parenteral10 MG
Injection, solutionCutaneous; Parenteral20 MG
Injection, solutionCutaneous; Parenteral30 MG
SolutionSubcutaneous10 mg
SolutionSubcutaneous20 mg
SolutionSubcutaneous30 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Not Available
Specific Function
Fibroblast growth factor receptor binding
Gene Name
FGF23
Uniprot ID
Q7Z4T2
Uniprot Name
Fibroblast growth factor 23
Molecular Weight
16440.335 Da
References
  1. Tardy B, Lecompte T, Boelhen F, Tardy-Poncet B, Elalamy I, Morange P, Gruel Y, Wolf M, Francois D, Racadot E, Camarasa P, Blouch MT, Nguyen F, Doubine S, Dutrillaux F, Alhenc-Gelas M, Martin-Toutain I, Bauters A, Ffrench P, de Maistre E, Grunebaum L, Mouton C, Huisse MG, Gouault-Heilmann M, Lucke V: Predictive factors for thrombosis and major bleeding in an observational study in 181 patients with heparin-induced thrombocytopenia treated with lepirudin. Blood. 2006 Sep 1;108(5):1492-6. Epub 2006 May 11. [PubMed:16690967]
  2. Kutilek S: Burosumab: A new drug to treat hypophosphatemic rickets. Sudan J Paediatr. 2017;17(2):71-73. doi: 10.24911/SJP.2017.2.11. [PubMed:29545670]
  3. Crysvita Drug Label [Link]
  4. Burosumab for XLH [Link]
  5. Burosumab for a rare bone disease [Link]
  6. DRUG: Burosumab [Link]

Drug created on April 18, 2018 09:27 / Updated on November 30, 2020 13:38

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