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

Stem definition	Drug id	CAS RN
humanized origin	5247	635715-01-4

Description:

Molecule	Description
Synonyms: inotuzumab ozogamicin inotuzumab ozogamicin (genetical recombination) besponsa CMC-544 WAY-207294	Inotuzumab ozogamicin is an antibody-drug conjugate (ADC) composed of a CD22-directed monoclonal antibody that is covalently linked to N-acetyl-gamma-calicheamicin dimethylhydrazide. Inotuzumab is a humanised immunoglobulin class G subtype 4 (IgG4) antibody that specifically recognises human CD22. The small molecule, N-acetyl-gamma-calicheamicin, is a cytotoxic product. N-acetyl-gamma-calicheamicin is covalently attached to the antibody via an acid-cleavable linker. Nonclinical data suggest that the anticancer activity of Inotuzumab ozogamicin is due to the binding of the ADC to CD22-expressing tumour cells, followed by internalisation of the ADC-CD22 complex, and the intracellular release of N-acetyl-gamma-calicheamicin dimethylhydrazide via hydrolytic cleavage of the linker. Activation of N-acetyl-gamma-calicheamicin dimethylhydrazide induces double-stranded DNA breaks, subsequently inducing cell cycle arrest and apoptotic cell death. Molecular weight: 1680.67 Formula: C73H96IInotuzumabN6O25S3 CLOGP: LIPINSKI: None HAC: None HDO: None TPSA: ALOGS: ROTB: None

Molecule

Description

Synonyms:

inotuzumab ozogamicin
inotuzumab ozogamicin (genetical recombination)
besponsa
CMC-544
WAY-207294

Inotuzumab ozogamicin is an antibody-drug conjugate (ADC) composed of a CD22-directed monoclonal antibody that is covalently linked to N-acetyl-gamma-calicheamicin dimethylhydrazide. Inotuzumab is a humanised immunoglobulin class G subtype 4 (IgG4) antibody that specifically recognises human CD22. The small molecule, N-acetyl-gamma-calicheamicin, is a cytotoxic product. N-acetyl-gamma-calicheamicin is covalently attached to the antibody via an acid-cleavable linker. Nonclinical data suggest that the anticancer activity of Inotuzumab ozogamicin is due to the binding of the ADC to CD22-expressing tumour cells, followed by internalisation of the ADC-CD22 complex, and the intracellular release of N-acetyl-gamma-calicheamicin dimethylhydrazide via hydrolytic cleavage of the linker. Activation of N-acetyl-gamma-calicheamicin dimethylhydrazide induces double-stranded DNA breaks, subsequently inducing cell cycle arrest and apoptotic cell death.

Molecular weight: 1680.67
Formula: C73H96IInotuzumabN6O25S3
CLOGP:
LIPINSKI: None
HAC: None
HDO: None
TPSA:
ALOGS:
ROTB: None

Drug dosage:

None

ADMET properties:

None

Approvals:

Date	Agency	Company
June 29, 2017	EMA	Pfizer Limited
Aug. 17, 2017	FDA	WYETH PHARMS INC
Jan. 19, 2018	PMDA	Pfizer Japan Inc

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
Venoocclusive liver disease	297.00	45	58	1648	4777	63482539
Acute lymphocytic leukaemia recurrent	219.98	45	40	1666	2229	63485087
Febrile neutropenia	196.07	45	84	1622	118365	63368951
Neoplasm progression	117.36	45	42	1664	36386	63450930
Babesiosis	94.28	45	14	1692	215	63487101
Neoplasm recurrence	93.04	45	20	1686	2618	63484698
Venoocclusive disease	80.52	45	17	1689	2041	63485275
Cytokine release syndrome	79.92	45	25	1681	14289	63473027
Neurotoxicity	63.85	45	22	1684	16968	63470348
Sepsis	50.93	45	38	1668	153085	63334231
Multiple organ dysfunction syndrome	46.61	45	25	1681	56727	63430589

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
Venoocclusive liver disease	391.77	32.65	98	2875	7868	34946090
Neoplasm progression	161.03	32.65	64	2909	23236	34930722
Acute lymphocytic leukaemia recurrent	152.08	32.65	38	2935	3006	34950952
Febrile neutropenia	130.24	32.65	101	2872	136748	34817210
Venoocclusive disease	119.61	32.65	31	2942	2836	34951122
Cytokine release syndrome	71.19	32.65	36	2937	22841	34931117
Blood bilirubin increased	46.83	32.65	33	2940	38263	34915695
Neutropenia	38.01	32.65	56	2917	156722	34797236
Corynebacterium infection	37.25	32.65	9	2964	616	34953342
Cytopenia	36.58	32.65	19	2954	12704	34941254
Pneumonia necrotising	35.34	32.65	9	2964	765	34953193
Blast cells present	33.90	32.65	8	2965	495	34953463
Thrombocytopenia	33.88	32.65	53	2920	156194	34797764
Neoplasm recurrence	33.78	32.65	11	2962	2238	34951720
Platelet count decreased	33.77	32.65	46	2927	119671	34834287
Lower respiratory tract infection	33.50	32.65	25	2948	31612	34922346
Hyperphosphataemia	33.42	32.65	13	2960	4424	34949534

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
Venoocclusive liver disease	660.28	39.71	150	4527	11621	79728090
Acute lymphocytic leukaemia recurrent	285.03	39.71	64	4613	4660	79735051
Febrile neutropenia	258.43	39.71	163	4514	230836	79508875
Neoplasm progression	236.21	39.71	95	4582	51587	79688124
Venoocclusive disease	186.00	39.71	45	4632	4528	79735183
Cytokine release syndrome	126.71	39.71	55	4622	35943	79703768
Neoplasm recurrence	114.31	39.71	30	4647	4184	79735527
Platelet count decreased	79.93	39.71	76	4601	194588	79545123
Blood bilirubin increased	79.31	39.71	49	4628	66183	79673528
Babesiosis	76.88	39.71	14	4663	349	79739362
Multiple organ dysfunction syndrome	69.43	39.71	57	4620	120189	79619522
Sepsis	67.64	39.71	81	4596	269347	79470364
Neurotoxicity	63.09	39.71	33	4644	32485	79707226
Ascites	57.04	39.71	42	4635	75520	79664191
Acute lymphocytic leukaemia	52.45	39.71	17	4660	4952	79734759
Graft versus host disease	49.71	39.71	22	4655	15004	79724707
Thrombocytopenia	46.67	39.71	67	4610	265192	79474519
Pyrexia	41.12	39.71	109	4568	678600	79061111
Thrombotic microangiopathy	40.63	39.71	21	4656	20148	79719563

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	L01FB01	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS MONOCLONAL ANTIBODIES AND ANTIBODY DRUG CONJUGATES CD22 (Clusters of Differentiation 22) inhibitors
FDA CS	M0028142	Immunoconjugates
FDA PE	N0000008576	Decreased DNA Integrity
FDA PE	N0000009176	Increased Cellular Death
MeSH PA	D000903	Antibiotics, Antineoplastic
MeSH PA	D000970	Antineoplastic Agents
MeSH PA	D000074322	Antineoplastic Agents, Immunological
MeSH PA	D018796	Immunoconjugates
MeSH PA	D007155	Immunologic Factors
MeSH PA	D000922	Immunotoxins
MeSH PA	D009676	Noxae
FDA MoA	N0000193616	CD22-directed Antibody Interactions
FDA EPC	N0000193617	CD22-directed Immunoconjugate

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

Disease	Relation	SNOMED_ID	DOID
Pre B-cell acute lymphoblastic leukemia	indication	277572006

🐶 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
B-cell receptor CD22	Membrane receptor	P20273	CD22_HUMAN	ANTIBODY BINDING	Kd	9.70		IUPHAR	DRUG LABEL

External reference:

ID	Source
P93RUU11P7	UNII
4036877	VANDF
C1567130	UMLSCUI
CHEMBL2108611	ChEMBL_ID
DB05889	DRUGBANK_ID
D08933	KEGG_DRUG
CHEMBL4297558	ChEMBL_ID
D000080045	MESH_DESCRIPTOR_UI
8574	INN_ID
8266	IUPHAR_LIGAND_ID
261074	MMSL
33023	MMSL
d08638	MMSL
017318	NDDF
736495009	SNOMEDCT_US
763600004	SNOMEDCT_US
1942950	RXNORM

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Besponsa	HUMAN PRESCRIPTION DRUG LABEL	1	0008-0100	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	0.25 mg	INTRAVENOUS	BLA	28 sections