Burosumab

Identification

Summary

Burosumab is a fibroblast growth factor 23 blocking antibody used to treat X-linked hypophosphatemia.

Brand Names

Crysvita

Generic Name

Burosumab

DrugBank Accession Number

DB14012

Background

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
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.

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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.

Target	Actions	Organism
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

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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.

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.

Drug	Interaction
Integrate drug-drug interactions in your software
Abciximab	The risk or severity of adverse effects can be increased when Abciximab is combined with Burosumab.
Adalimumab	The risk or severity of adverse effects can be increased when Adalimumab is combined with Burosumab.
Aducanumab	The risk or severity of adverse effects can be increased when Aducanumab is combined with Burosumab.
Alemtuzumab	The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Burosumab.
Alirocumab	The risk or severity of adverse effects can be increased when Alirocumab is combined with Burosumab.
Amivantamab	The risk or severity of adverse effects can be increased when Burosumab is combined with Amivantamab.
Anifrolumab	The risk or severity of adverse effects can be increased when Anifrolumab is combined with Burosumab.
Ansuvimab	The risk or severity of adverse effects can be increased when Burosumab is combined with Ansuvimab.
Anthrax immune globulin human	The 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.

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Food Interactions

No interactions found.

Products

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Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Crysvita	Injection, solution	10 mg/ml	Subcutaneous	Kyowa Kirin Holdings B.V.	2021-02-10	Not applicable
Crysvita	Solution	10 mg / mL	Subcutaneous	Kyowa Kirin, Inc.	2019-01-28	Not applicable
Crysvita	Injection	10 mg/1mL	Subcutaneous	Ultragenyx Pharmaceutical Inc.	2018-04-18	Not applicable
Crysvita	Injection, solution	30 mg/ml	Subcutaneous	Kyowa Kirin Holdings B.V.	2021-02-10	Not applicable
Crysvita	Solution	30 mg / mL	Subcutaneous	Kyowa Kirin, Inc.	2019-01-28	Not applicable
Crysvita	Injection	20 mg/1mL	Subcutaneous	Ultragenyx Pharmaceutical Inc.	2018-04-18	Not applicable
Crysvita	Injection, solution	20 mg/ml	Subcutaneous	Kyowa Kirin Holdings B.V.	2021-02-10	Not applicable
Crysvita	Solution	20 mg / mL	Subcutaneous	Kyowa Kirin, Inc.	2019-01-28	Not applicable
Crysvita	Injection	30 mg/1mL	Subcutaneous	Ultragenyx Pharmaceutical Inc.	2018-04-18	Not applicable

Chemical Identifiers

UNII: G9WJT6RD29
CAS number: 1610833-03-8

References

General References

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. [Article]
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. [Article]
FDA approves first therapy for rare inherited form of rickets, x-linked hypophosphatemia [Link]
Crysvita Drug Label [Link]
Burosumab for a rare bone disease [Link]
DRUG: Burosumab [Link]
NHS document [Link]
Burosumab for XLH [Link]

External Links

KEGG Drug: D10913
RxNav: 2043855
Wikipedia: Burosumab

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Completed	Other	X-linked Hypophosphatemia (XLH)	1
4	Completed	Treatment	Epidermal Nevus Syndrome (ENS)	1
4	Recruiting	Treatment	Tumor-induced Osteomalacia (TIO)	1
4	Recruiting	Treatment	X-linked Hypophosphatemia (XLH)	2
4	Unknown Status	Treatment	Rare Disorders / X-linked Hypophosphatemia (XLH)	1
3	Active Not Recruiting	Treatment	X-linked Hypophosphatemia (XLH)	1
3	Completed	Treatment	Hypophosphatemia / Hypophosphatemic Rickets / Pain, Chronic	1
3	Completed	Treatment	X-linked Hypophosphatemia (XLH)	5
3	Completed	Treatment	X-linked Hypophosphatemic Rickets/Osteomalacia	1
2	Completed	Treatment	Epidermal Nevus Syndrome (ENS) / Tumor-induced Osteomalacia (TIO)	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection	Subcutaneous	10 mg/1mL
Injection	Subcutaneous	20 mg/1mL
Injection	Subcutaneous	30 mg/1mL
Injection, solution	Subcutaneous	10 mg/mL
Injection, solution	Subcutaneous	20 mg/mL
Injection, solution	Subcutaneous	30 mg/mL
Solution	Subcutaneous	10 mg / mL
Solution	Subcutaneous	20 mg / mL
Solution	Subcutaneous	30 mg / mL
Solution	Subcutaneous	10 mg
Solution	Subcutaneous	20 mg
Solution	Subcutaneous	30 mg

Prices

Not Available

Patents

Not Available

Properties

State: Solid
Experimental Properties: Not Available

Targets

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Details1. Fibroblast growth factor 23

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

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. [Article]
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. [Article]
Crysvita Drug Label [Link]
Burosumab for XLH [Link]
Burosumab for a rare bone disease [Link]
DRUG: Burosumab [Link]

Drug created at April 18, 2018 15:27 / Updated at April 01, 2022 20:23

Burosumab

Identification

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Targets

References