Benralizumab

Identification

Summary

Benralizumab is a monoclonal antibody used to treat eosinophilic asthma.

Brand Names

Fasenra

Generic Name

Benralizumab

DrugBank Accession Number

DB12023

Background

Benralizumab is a humanized recombinant monoclonal antibody of the isotype IgG1k immunoglobulin that specifically binds to the alpha chain of the interleukin 5 receptor (IL-5R) expressed on eosinophils and basophils.² It inhibits the binding of IL-5 as well as the hetero-oligomerization of the alpha and beta subunits of the IL-5R, thus blocking, signal transduction. Besides, it is an afucosylated IgG which gives it high affinity for the FcγRIIIα receptor in natural killer cells, macrophages and neutrophils.¹ Benralizumab, FDA approved on November 14, 2017, was developed by MedImmune, the AstraZeneca's global biologic research and development arm.⁶

Type

Biotech

Groups

Approved, Investigational

Biologic Classification

Protein Based Therapies
Monoclonal antibody (mAb)

Protein Structure

Protein Chemical Formula: C₆₄₉₂H₁₀₀₆₀N₁₇₂₄O₂₀₂₈S₄₂
Protein Average Weight: 146054.0 Da

Sequences

>Heavy chain 
EVQLVQSGAEVKKPGASVKVSCKASGYTFTSYVIHWVRQRPGQGLAWMGYINPYNDGTKY
NERFKGKVTITSDRSTSTVYMELSSLRSEDTAVYLCGREGIRYYGLLGDYWGQGTLVTVS
SASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS
SGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLG
GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY
NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD
ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR
WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

>Light chain
DIQMTQSPSSLSASVGDRVTITCGTSEDIINYLNWYQQKPGKAPKLLIYHTSRLQSGVPS
RFSGSGSGTDFTLTISSLQPEDFATYYCQQGYTLPYTFGQGTKVEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

Download FASTA Format

Synonyms

Benralizumab

External IDs

BIW-8405
MEDI-563

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Pharmacology

Indication

Benralizumab is indicated as a maintenance treatment of patients 12 years or older with severe asthma and an eosinophilic phenotype.⁷ The pathology of severe asthma with eosinophilic phenotype is also denotated as TH2-high phenotype. The patients with this phenotype are characterized by the expression of IL-5 and IL-13, airway hyperresponsiveness, responsiveness to inhaled corticosteroids, high serum IgE and eosinophilia in blood and airway. In the TH2-high phenotype, IL-5 presents a central role as it is responsible for eosinophil differentiation, survival, activation and migration to the lungs.³

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Adjunct therapy in treatment of	Severe eosinophilic asthma		••••••••••••

Contraindications & Blackbox Warnings

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Pharmacodynamics

Eosinophils are the key target of inflammatory respiratory diseases and they undergo apoptosis in absence of IL-5. Therefore, benralizumab action on the IL-5 receptor in basophils and eosinophils produces the apoptosis and its significant reduction in the blood.² On the other hand, Benralizumab binding to natural killer cells FcγRIIIα receptor produces a direct antibody-dependent cell-mediated cytotoxicity. All these effects produce a reduction in eosinophil count in airway mucosa, submucosa, sputum, blood and bone marrow.⁴

Mechanism of action

Interleukin-5 (IL-5) induces an eosinophil-mediated inflammatory response by binding to the IL-5 receptor (IL-5R) expressed in eosinophils, basophils and some mast cells. Benralizumab, unlike IL-5 low-affinity binding, binds with high affinity to the domain I of the α-chain of IL-5R and blocks its signaling and the proliferation of IL-5-dependent cell lines. On the other hand, Benralizumab is an afucosylated antibody in the CH2 region which gives it a high affinity for the FcγRIIIa on natural killer cells, macrophages and neutrophils. This binding triggers a magnified apoptosis response in eosinophils via antibody-dependent cell-mediated cytotoxicity.^1,3

Target	Actions	Organism
AInterleukin-5 receptor subunit alpha	antibody	Humans
ALow affinity immunoglobulin gamma Fc region receptor III-A	binding	Humans

Absorption

Subcutaneous administration of Benralizumab presented a dose-proportional pharmacokinetic profile. The administration of 20-200 mg presented an absorption half-life of 3.6 days with a bioavailability of 58%.^Label It is also reported for Benralizumab a Cmax of 82 mcg/ml and AUC of 775 mcg day/ml.¹

Volume of distribution

Pharmacokinetic reports of Benralizumab showed a volume of distribution in a range of 52-93ml/kg. For a 70kg individual, the central volume of distribution of Benralizumab is 3.2 L while the peripheral volume of distribution is reported to be 2.5 L.⁵

Protein binding

There is no reports indicating that Benralizumab binds to plasma proteins.

Metabolism

As any monoclonal IgG antibody, Beralizumab is degraded by proteases widely spread in the body. ^Label

Route of elimination

Benraluzimab presents a linear pharmacokinetic without target-receptor mediated clearance.^Label The presence of a dose-proportional pharmacokinetics suggests a rapid depletion of the target and an elimination mainly mediated through the reticuloendothelial system.⁵

Half-life

The half-life of Benralizumab is estimated to be 15-18 days.¹

Clearance

For a subject weighting 70kg, the typical systemic clearance is 0.29L/day.^Label

Adverse Effects

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Toxicity

There are not reports of long-term studies regarding tumorgenesis or carcinogenesis. Fertility studies performed in aminal trials showed no adverse histopathological findings.^Label

Pathways

Not Available

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Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">

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
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Abciximab	The risk or severity of adverse effects can be increased when Abciximab is combined with Benralizumab.
Adalimumab	The risk or severity of adverse effects can be increased when Adalimumab is combined with Benralizumab.
Aducanumab	The risk or severity of adverse effects can be increased when Benralizumab is combined with Aducanumab.
Alemtuzumab	The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Benralizumab.
Alirocumab	The risk or severity of adverse effects can be increased when Alirocumab is combined with Benralizumab.

Food Interactions

No interactions found.

Products

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Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Fasenra	Injection, solution	30 mg/1mL	Subcutaneous	AstraZeneca Pharmaceuticals LP	2017-11-14	Not applicable
Fasenra	Injection, solution	30 mg	Subcutaneous	Astra Zeneca Ab	2020-12-16	Not applicable
Fasenra	Solution	30 mg / mL	Subcutaneous	Astra Zeneca	2018-03-28	Not applicable
Fasenra	Injection, solution	30 mg	Subcutaneous	Astra Zeneca Ab	2020-12-16	Not applicable
Fasenra	Injection, solution	30 mg/1mL	Subcutaneous	AstraZeneca Pharmaceuticals LP	2019-10-04	Not applicable

Chemical Identifiers

UNII: 71492GE1FX
CAS number: 1044511-01-4

References

General References

Ghazi A, Trikha A, Calhoun WJ: Benralizumab--a humanized mAb to IL-5Ralpha with enhanced antibody-dependent cell-mediated cytotoxicity--a novel approach for the treatment of asthma. Expert Opin Biol Ther. 2012 Jan;12(1):113-8. doi: 10.1517/14712598.2012.642359. Epub 2011 Dec 5. [Article]
Laviolette M, Gossage DL, Gauvreau G, Leigh R, Olivenstein R, Katial R, Busse WW, Wenzel S, Wu Y, Datta V, Kolbeck R, Molfino NA: Effects of benralizumab on airway eosinophils in asthmatic patients with sputum eosinophilia. J Allergy Clin Immunol. 2013 Nov;132(5):1086-1096.e5. doi: 10.1016/j.jaci.2013.05.020. Epub 2013 Jul 16. [Article]
Bagnasco D, Ferrando M, Varricchi G, Puggioni F, Passalacqua G, Canonica GW: Anti-Interleukin 5 (IL-5) and IL-5Ra Biological Drugs: Efficacy, Safety, and Future Perspectives in Severe Eosinophilic Asthma. Front Med (Lausanne). 2017 Aug 31;4:135. doi: 10.3389/fmed.2017.00135. eCollection 2017. [Article]
Tan LD, Bratt JM, Godor D, Louie S, Kenyon NJ: Benralizumab: a unique IL-5 inhibitor for severe asthma. J Asthma Allergy. 2016 Apr 4;9:71-81. doi: 10.2147/JAA.S78049. eCollection 2016. [Article]
Wang B, Yan L, Yao Z, Roskos LK: Population Pharmacokinetics and Pharmacodynamics of Benralizumab in Healthy Volunteers and Patients With Asthma. CPT Pharmacometrics Syst Pharmacol. 2017 Apr;6(4):249-257. doi: 10.1002/psp4.12160. Epub 2017 Jan 21. [Article]
Newswire [Link]
Astra Zeneca news [Link]

External Links

PubChem Substance: 347911271
Wikipedia: Benralizumab

FDA label

Download (858 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
4	Active Not Recruiting	Treatment	Asthma	1
4	Completed	Treatment	Asthma / Severe Eosinophilic Asthma	1
4	Completed	Treatment	Chronic Idiopathic Urticaria	1
4	Completed	Treatment	In Adult Patients of Severe Asthma With Eosinophilic Phenotype in India	1
4	Recruiting	Other	Eosinophilic Asthma / Severe Asthma	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection, solution	Parenteral; Subcutaneous	30 MG
Injection, solution	Subcutaneous	30 mg
Injection, solution	Subcutaneous	30 mg/1mL
Solution	Subcutaneous	30 mg / mL
Injection, solution	Subcutaneous
Injection, solution		30 mg/ml
Solution	Subcutaneous	30 mg
Injection, solution	Subcutaneous	30 mg/ml
Injection, solution		30 mg/1ml

Prices

Not Available

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	69 °C (midpoint transition), 80 °C (whole IgG1)	Dashivets, et al. PLOS ONE. 10. e0143520. 10.1371/journal.pone.0143520. (2015).
isoelectric point	6.6 - 7.2	Jin, et al. Electrophoresis. Sep;23(19):3385-91. (2002).

Targets

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Details1. Interleukin-5 receptor subunit alpha

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Antibody

General Function: Interleukin-5 receptor activity
Specific Function: This is the receptor for interleukin-5. The alpha chain binds to IL5.
Gene Name: IL5RA
Uniprot ID: Q01344
Uniprot Name: Interleukin-5 receptor subunit alpha
Molecular Weight: 47684.225 Da

References

Ghazi A, Trikha A, Calhoun WJ: Benralizumab--a humanized mAb to IL-5Ralpha with enhanced antibody-dependent cell-mediated cytotoxicity--a novel approach for the treatment of asthma. Expert Opin Biol Ther. 2012 Jan;12(1):113-8. doi: 10.1517/14712598.2012.642359. Epub 2011 Dec 5. [Article]
Laviolette M, Gossage DL, Gauvreau G, Leigh R, Olivenstein R, Katial R, Busse WW, Wenzel S, Wu Y, Datta V, Kolbeck R, Molfino NA: Effects of benralizumab on airway eosinophils in asthmatic patients with sputum eosinophilia. J Allergy Clin Immunol. 2013 Nov;132(5):1086-1096.e5. doi: 10.1016/j.jaci.2013.05.020. Epub 2013 Jul 16. [Article]
Bagnasco D, Ferrando M, Varricchi G, Puggioni F, Passalacqua G, Canonica GW: Anti-Interleukin 5 (IL-5) and IL-5Ra Biological Drugs: Efficacy, Safety, and Future Perspectives in Severe Eosinophilic Asthma. Front Med (Lausanne). 2017 Aug 31;4:135. doi: 10.3389/fmed.2017.00135. eCollection 2017. [Article]

Details2. Low affinity immunoglobulin gamma Fc region receptor III-A

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Binding

General Function: Not Available
Specific Function: Receptor for the Fc region of IgG. Binds complexed or aggregated IgG and also monomeric IgG. Mediates antibody-dependent cellular cytotoxicity (ADCC) and other antibody-dependent responses, such as...
Gene Name: FCGR3A
Uniprot ID: P08637
Uniprot Name: Low affinity immunoglobulin gamma Fc region receptor III-A
Molecular Weight: 29088.895 Da

References

Ghazi A, Trikha A, Calhoun WJ: Benralizumab--a humanized mAb to IL-5Ralpha with enhanced antibody-dependent cell-mediated cytotoxicity--a novel approach for the treatment of asthma. Expert Opin Biol Ther. 2012 Jan;12(1):113-8. doi: 10.1517/14712598.2012.642359. Epub 2011 Dec 5. [Article]
Laviolette M, Gossage DL, Gauvreau G, Leigh R, Olivenstein R, Katial R, Busse WW, Wenzel S, Wu Y, Datta V, Kolbeck R, Molfino NA: Effects of benralizumab on airway eosinophils in asthmatic patients with sputum eosinophilia. J Allergy Clin Immunol. 2013 Nov;132(5):1086-1096.e5. doi: 10.1016/j.jaci.2013.05.020. Epub 2013 Jul 16. [Article]
Wang B, Yan L, Yao Z, Roskos LK: Population Pharmacokinetics and Pharmacodynamics of Benralizumab in Healthy Volunteers and Patients With Asthma. CPT Pharmacometrics Syst Pharmacol. 2017 Apr;6(4):249-257. doi: 10.1002/psp4.12160. Epub 2017 Jan 21. [Article]

Drug created at October 20, 2016 21:11 / Updated at June 03, 2022 07:24

Benralizumab

Identification

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Targets

References

References