benralizumab 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
humanized origin	5263	1044511-01-4

Description:

Molecule	Description
Molfile Synonyms: benralizumab MEDI-563 fasenra	Benralizumab is a humanized afucosylated, monoclonal antibody (IgG1, kappa) that directly binds to the alpha subunit of the human interleukin-5 receptor (IL-5Ralpha) with a dissociation constant of 11 pM. The IL-5 receptor is expressed on the surface of eosinophils and basophils. In an in vitro setting, the absence of fucose in the Fc domain of benralizumab facilitates binding (45.5 nM) to FcɣRIII receptors on immune effectors cells, such as natural killer (NK) cells, leading to apoptosis of eosinophils and basophils through antibody-dependent cell-mediated cytotoxicity (ADCC). Inflammation is an important component in the pathogenesis of asthma. Multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) are involved in inflammation. Benralizumab, by binding to the IL-5Ralpha chain, reduces eosinophils through ADCC; however, the mechanism of benralizumab action in asthma has not been definitively established. Molecular weight: Formula: CLOGP: LIPINSKI: None HAC: None HDO: None TPSA: ALOGS: ROTB: None

Molecule

Description

Molfile

Synonyms:

benralizumab
MEDI-563
fasenra

Benralizumab is a humanized afucosylated, monoclonal antibody (IgG1, kappa) that directly binds to the alpha subunit of the human interleukin-5 receptor (IL-5Ralpha) with a dissociation constant of 11 pM. The IL-5 receptor is expressed on the surface of eosinophils and basophils. In an in vitro setting, the absence of fucose in the Fc domain of benralizumab facilitates binding (45.5 nM) to FcɣRIII receptors on immune effectors cells, such as natural killer (NK) cells, leading to apoptosis of eosinophils and basophils through antibody-dependent cell-mediated cytotoxicity (ADCC). Inflammation is an important component in the pathogenesis of asthma. Multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) are involved in inflammation. Benralizumab, by binding to the IL-5Ralpha chain, reduces eosinophils through ADCC; however, the mechanism of benralizumab action in asthma has not been definitively established.

Molecular weight:
Formula:
CLOGP:
LIPINSKI: None
HAC: None
HDO: None
TPSA:
ALOGS:
ROTB: None

Drug dosage:

Dose	Unit	Route
0.54	mg	P

ADMET properties:

None

Approvals:

Date	Agency	Company
Jan. 8, 2018	EMA	AstraZeneca AB
Nov. 17, 2017	FDA	ASTRAZENECA AB
Jan. 19, 2018	PMDA	AstraZeneca KK

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Wheezing	257.75	26.25	152	7245	95443	63386182
Asthma	236.52	26.25	160	7237	127401	63354224
Eosinophil count increased	184.33	26.25	63	7334	10865	63470760
Dyspnoea	136.82	26.25	261	7136	661052	62820573
Cough	122.50	26.25	160	7237	292583	63189042
Headache	106.97	26.25	230	7167	633011	62848614
Urticaria	106.52	26.25	113	7284	165689	63315936
Obstructive airways disorder	92.16	26.25	46	7351	20653	63460972
Chest discomfort	90.92	26.25	86	7311	109883	63371742
Death	87.28	26.25	156	7241	374225	63107400
Symptom recurrence	80.49	26.25	22	7375	1788	63479837
Eosinophilic granulomatosis with polyangiitis	76.32	26.25	22	7375	2170	63479455
COVID-19	74.16	26.25	78	7319	113025	63368600
Device leakage	68.00	26.25	27	7370	7069	63474556
Full blood count abnormal	63.88	26.25	42	7355	31675	63449950
Middle insomnia	58.94	26.25	29	7368	12614	63469011
Therapeutic product effect incomplete	57.83	26.25	72	7325	124984	63356641
Incorrect dose administered by device	57.75	26.25	21	7376	4327	63477298
Injection site pain	57.27	26.25	73	7324	129727	63351898
Pruritus	55.79	26.25	127	7270	361326	63120299
Eosinophilia	47.93	26.25	31	7366	22725	63458900
Chills	45.69	26.25	61	7336	113317	63368308
Asthmatic crisis	44.94	26.25	14	7383	1799	63479826
Blood immunoglobulin E increased	41.66	26.25	16	7381	3833	63477792
Atrial flutter	41.38	26.25	21	7376	9751	63471874
Sinus disorder	41.08	26.25	29	7368	24524	63457101
Pyrexia	41.02	26.25	134	7263	470344	63011281
Bacterial disease carrier	40.35	26.25	12	7385	1319	63480306
Eosinophil count abnormal	39.91	26.25	10	7387	578	63481047
Inappropriate schedule of product administration	38.95	26.25	54	7343	103911	63377714
Anaphylactic reaction	38.74	26.25	43	7354	66057	63415568
Productive cough	36.84	26.25	41	7356	63167	63418458
Rash	35.55	26.25	144	7253	560727	62920898
Forced expiratory volume decreased	34.42	26.25	15	7382	4953	63476672
Sputum discoloured	33.76	26.25	22	7375	16325	63465300
Hypersensitivity	32.64	26.25	91	7306	292594	63189031
Wrong technique in device usage process	32.08	26.25	13	7384	3585	63478040
Respiratory tract congestion	32.02	26.25	22	7375	17810	63463815
Condition aggravated	31.86	26.25	111	7286	402106	63079519
Rash pruritic	31.81	26.25	37	7360	59762	63421863
Malaise	31.41	26.25	113	7284	415841	63065784
Bronchial wall thickening	30.66	26.25	10	7387	1489	63480136
Oropharyngeal pain	29.45	26.25	45	7352	94442	63387183
Product dose omission issue	29.28	26.25	76	7321	234237	63247388
Bronchial secretion retention	28.14	26.25	11	7386	2762	63478863

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Asthma	122.57	36.40	61	2565	42595	34911710
Dyspnoea	95.40	36.40	128	2498	376654	34577651
Wheezing	95.21	36.40	51	2575	41351	34912954
Eosinophilic granulomatosis with polyangiitis	88.09	36.40	22	2604	1965	34952340
Eosinophil count increased	56.42	36.40	22	2604	8550	34945755
Headache	50.07	36.40	68	2558	200567	34753738
Eosinophil count abnormal	44.54	36.40	9	2617	305	34954000
Death	44.37	36.40	94	2532	397955	34556350
Drug ineffective	43.22	36.40	101	2525	456650	34497655
Urticaria	40.24	36.40	35	2591	62342	34891963
Myalgia	38.51	36.40	39	2587	84071	34870234
Nasal congestion	38.30	36.40	23	2603	23034	34931271
Nasal polyps	38.09	36.40	12	2614	2491	34951814
Arthralgia	36.95	36.40	54	2572	169987	34784318

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Wheezing	221.07	28.14	132	6627	116532	79621097
Asthma	218.16	28.14	138	6621	134957	79602672
Eosinophilic granulomatosis with polyangiitis	140.32	28.14	37	6722	3623	79734006
Dyspnoea	128.98	28.14	246	6513	856779	78880850
Eosinophil count increased	125.12	28.14	49	6710	17056	79720573
Cough	105.71	28.14	142	6617	366647	79370982
Urticaria	101.39	28.14	100	6659	185101	79552528
Headache	87.45	28.14	179	6580	653593	79084036
Chest discomfort	74.48	28.14	74	6685	137970	79599659
Obstructive airways disorder	71.10	28.14	40	6719	31419	79706210
Device leakage	55.23	28.14	24	6735	10832	79726797
Therapeutic product effect incomplete	53.64	28.14	63	6696	141582	79596047
Pyrexia	52.90	28.14	151	6608	678558	79059071
Pruritus	50.10	28.14	106	6653	394542	79343087
Incorrect dose administered by device	49.97	28.14	18	6741	4971	79732658
Chills	48.98	28.14	64	6695	160170	79577459
COVID-19	46.68	28.14	62	6697	157612	79580017
Eosinophil count abnormal	45.75	28.14	11	6748	740	79736889
Anaphylactic reaction	45.31	28.14	45	6714	83698	79653931
Hypersensitivity	43.65	28.14	79	6680	262160	79475469
Middle insomnia	43.41	28.14	23	6736	16046	79721583
Full blood count abnormal	40.73	28.14	31	6728	40443	79697186
Blood immunoglobulin E increased	40.02	28.14	16	6743	5866	79731763
Bronchial obstruction	39.44	28.14	13	6746	2755	79734874
Bacterial disease carrier	37.87	28.14	11	6748	1535	79736094
Rash pruritic	37.84	28.14	38	6721	71591	79666038
Sputum discoloured	36.93	28.14	23	6736	21720	79715909
Injection site pain	36.80	28.14	50	6709	129788	79607841
Productive cough	36.29	28.14	41	6718	88290	79649339
Sinus disorder	36.24	28.14	23	6736	22441	79715188
Myalgia	36.19	28.14	60	6699	185581	79552048
Asthmatic crisis	35.05	28.14	11	6748	1995	79735634
Eosinophilia	33.50	28.14	29	6730	45316	79692313
Malaise	33.31	28.14	104	6655	489765	79247864
Rash	32.41	28.14	115	6644	578243	79159386
Death	32.04	28.14	113	6646	566401	79171228
Respiratory tract congestion	31.12	28.14	20	6739	19934	79717695
Wrong technique in device usage process	31.07	28.14	12	6747	4016	79733613
Respiratory tract infection	29.78	28.14	28	6731	48661	79688968
Atrial flutter	29.65	28.14	20	6739	21605	79716024
Nasal congestion	28.86	28.14	34	6725	76518	79661111
Acute kidney injury	28.26	28.14	5	6754	519399	79218230

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	R03DX10	RESPIRATORY SYSTEM DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES OTHER SYSTEMIC DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES Other systemic drugs for obstructive airway diseases
MeSH PA	D018927	Anti-Asthmatic Agents
MeSH PA	D019141	Respiratory System Agents
FDA MoA	N0000193802	Interleukin 5 Receptor alpha-directed Antibody Interactions
FDA EPC	N0000193803	Interleukin-5 Receptor alpha-directed Cytolytic Antibody

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
Eosinophilic asthma	indication	367542003	DOID:9498

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Interleukin-5 receptor subunit alpha	Membrane receptor	Q01344	IL5RA_HUMAN	ANTIBODY BINDING	Kd	10.96		DRUG LABEL	DRUG LABEL

External reference:

ID	Source
71492GE1FX	UNII
4037103	VANDF
C2982078	UMLSCUI
CHEMBL1742991	ChEMBL_ID
DB12023	DRUGBANK_ID
D09874	KEGG_DRUG
9233	INN_ID
7674	IUPHAR_LIGAND_ID
265443	MMSL
33253	MMSL
d08675	MMSL
017409	NDDF
763651005	SNOMEDCT_US
763652003	SNOMEDCT_US
1989100	RXNORM
C571386	MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
FASENRA	HUMAN PRESCRIPTION DRUG LABEL	1	0310-1730	INJECTION, SOLUTION	30 mg	SUBCUTANEOUS	BLA	27 sections
FASENRA	HUMAN PRESCRIPTION DRUG LABEL	1	0310-1730	INJECTION, SOLUTION	30 mg	SUBCUTANEOUS	BLA	27 sections
FASENRA	HUMAN PRESCRIPTION DRUG LABEL	1	0310-1730	INJECTION, SOLUTION	30 mg	SUBCUTANEOUS	BLA	27 sections
FASENRA	HUMAN PRESCRIPTION DRUG LABEL	1	0310-1830	INJECTION, SOLUTION	30 mg	SUBCUTANEOUS	BLA	27 sections
FASENRA	HUMAN PRESCRIPTION DRUG LABEL	1	0310-1830	INJECTION, SOLUTION	30 mg	SUBCUTANEOUS	BLA	27 sections
FASENRA	HUMAN PRESCRIPTION DRUG LABEL	1	0310-1830	INJECTION, SOLUTION	30 mg	SUBCUTANEOUS	BLA	27 sections