Burosumab
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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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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Hypophosphatemia •••••••••••• •••••••••••• ••••••••••• ••••• Treatment of X-linked hypophosphataemia •••••••••••• - 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 antagonistHumans - 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 softwareAbciximab 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. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Crysvita Injection, solution 20 mg/ml Subcutaneous Kyowa Kirin Holdings B.V. 2021-02-10 Not applicable EU Crysvita Injection 20 mg/1mL Subcutaneous Kyowa Kirin Malaysia Sdn. Bhd. 2018-04-18 Not applicable US Crysvita Injection 10 mg/1mL Subcutaneous Ultragenyx Pharmaceutical Inc. 2018-04-18 Not applicable US Crysvita Solution 20 mg / mL Subcutaneous Kyowa Kirin Malaysia Sdn. Bhd. 2019-01-28 Not applicable Canada Crysvita Injection 20 mg/1mL Subcutaneous Ultragenyx Pharmaceutical Inc. 2018-04-18 Not applicable US
Categories
- ATC Codes
- M05BX05 — Burosumab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Blood Proteins
- Drugs Affecting Bone Structure and Mineralization
- Drugs for Treatment of Bone Diseases
- Fibroblast Growth Factor-23 Blocking Antibodies
- Globulins
- Immunoglobulins
- Immunoproteins
- Musculo-Skeletal System
- Proteins
- Serum Globulins
- 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
- Affected organisms
- Humans and other mammals
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
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Available Not Available Tumor-induced Osteomalacia (TIO) / X-Linked Hypophosphatemia 1 somestatus stop reason just information to hide Not Available Completed Not Available X-Linked Hypophosphatemia 1 somestatus stop reason just information to hide 4 Completed Other X-Linked Hypophosphatemia 1 somestatus stop reason just information to hide 4 Completed Treatment Epidermal Nevus Syndrome (ENS) 1 somestatus stop reason just information to hide 4 Completed Treatment Tumor-induced Osteomalacia (TIO) 1 somestatus stop reason just information to hide
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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Not Available
- Specific Function
- Not Available
- 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