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

Stem definitionDrug idCAS RN
humanized origin 5247 635715-01-4

Description:

MoleculeDescription

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

Predicted pharmacokinetic/toxicological properties (PK-AZ):

None

Approvals:

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

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Venoocclusive liver disease 416.24 48.15 79 2228 5914 90620226
Acute lymphocytic leukaemia recurrent 306.28 48.15 54 2253 2667 90623473
Febrile neutropenia 233.71 48.15 102 2205 158247 90467893
Neoplasm progression 129.70 48.15 47 2260 44439 90581701
Neoplasm recurrence 117.93 48.15 25 2282 3234 90622906
Cytokine release syndrome 106.22 48.15 36 2271 27937 90598203
Venoocclusive disease 101.32 48.15 21 2286 2434 90623706
Babesiosis 91.96 48.15 14 2293 271 90625869
Neurotoxicity 90.90 48.15 30 2277 21437 90604703
Sepsis 67.44 48.15 47 2260 179767 90446373
Blood bilirubin increased 54.17 48.15 25 2282 43445 90582695
Multiple organ dysfunction syndrome 51.69 48.15 28 2279 68308 90557832
Escherichia bacteraemia 50.07 48.15 14 2293 5721 90620419
Platelet count decreased 49.43 48.15 35 2272 136934 90489206

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Venoocclusive liver disease 488.12 32.48 125 3798 10177 42607235
Acute lymphocytic leukaemia recurrent 200.24 32.48 50 3873 3641 42613771
Venoocclusive disease 187.46 32.48 48 3875 3867 42613545
Neoplasm progression 168.52 32.48 72 3851 28928 42588484
Cytokine release syndrome 127.63 32.48 68 3855 44459 42572953
Febrile neutropenia 126.43 32.48 117 3806 185586 42431826
Cytopenia 62.40 32.48 31 3892 17466 42599946
Thrombocytopenia 47.68 32.48 72 3851 190207 42427205
Leukaemic infiltration extramedullary 47.66 32.48 9 3914 172 42617240
Blood bilirubin increased 43.72 32.48 34 3889 42218 42575194
Immune effector cell-associated neurotoxicity syndrome 43.60 32.48 20 3903 9441 42607971
Graft versus host disease 40.53 32.48 21 3902 12904 42604508
Platelet count decreased 39.84 32.48 56 3867 138525 42478887
Acute lymphocytic leukaemia 39.42 32.48 14 3909 3417 42613995
Neoplasm recurrence 38.60 32.48 13 3910 2711 42614701
Neutropenia 38.41 32.48 67 3856 199364 42418048
Corynebacterium infection 33.46 32.48 9 3914 874 42616538
Blast cells present 33.12 32.48 8 3915 505 42616907

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Venoocclusive liver disease 866.65 34.90 195 6056 15012 110568036
Acute lymphocytic leukaemia recurrent 394.09 34.90 86 6165 5701 110577347
Febrile neutropenia 300.80 34.90 199 6052 316568 110266480
Neoplasm progression 272.59 34.90 111 6140 64484 110518564
Venoocclusive disease 232.47 34.90 57 6194 6293 110576755
Cytokine release syndrome 224.02 34.90 99 6152 70207 110512841
Neoplasm recurrence 142.08 34.90 37 6214 5195 110577853
Neurotoxicity 107.75 34.90 51 6200 42156 110540892
Platelet count decreased 103.35 34.90 93 6158 230350 110352698
Blood bilirubin increased 100.13 34.90 59 6192 75913 110507135
Sepsis 79.39 34.90 95 6156 327251 110255797
Thrombocytopenia 76.13 34.90 96 6155 348789 110234259
Babesiosis 73.06 34.90 14 6237 481 110582567
Ascites 72.70 34.90 52 6199 92756 110490292
Cytopenia 72.61 34.90 35 6216 30081 110552967
Immune effector cell-associated neurotoxicity syndrome 71.23 34.90 28 6223 14754 110568294
Acute lymphocytic leukaemia 71.04 34.90 22 6229 5743 110577305
Multiple organ dysfunction syndrome 69.46 34.90 62 6189 151648 110431400
Graft versus host disease 61.46 34.90 27 6224 18779 110564269
Neutrophil count decreased 60.51 34.90 52 6199 120889 110462159
Leukaemic infiltration extramedullary 52.23 34.90 10 6241 342 110582706
Neutropenia 51.86 34.90 83 6168 374537 110208511
Thrombotic microangiopathy 50.21 34.90 27 6224 29122 110553926
Pyrexia 49.36 34.90 136 6115 898129 109684919
Lymphocyte count decreased 46.94 34.90 33 6218 57210 110525838
White blood cell count decreased 42.02 34.90 58 6193 229332 110353716
Central nervous system leukaemia 41.41 34.90 9 6242 582 110582466
Enterococcal infection 41.16 34.90 21 6230 20345 110562703
Death 40.50 34.90 108 6143 698761 109884287
Mucosal inflammation 39.49 34.90 37 6214 96104 110486944
Tumour lysis syndrome 38.14 34.90 23 6228 30778 110552270
Acute lymphocytic leukaemia refractory 37.74 34.90 7 6244 201 110582847
Blast cells present 36.90 34.90 9 6242 969 110582079
Hepatobiliary disease 36.16 34.90 9 6242 1053 110581995
Myelopathy 35.68 34.90 13 6238 5563 110577485
Hyperglycaemia 35.43 34.90 33 6218 85057 110497991

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
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 D000922 Immunotoxins
MeSH PA D000074322 Antineoplastic Agents, Immunological
MeSH PA D000903 Antibiotics, Antineoplastic
MeSH PA D000970 Antineoplastic Agents
MeSH PA D007155 Immunologic Factors
FDA MoA N0000193616 CD22-directed Antibody Interactions
FDA EPC N0000193617 CD22-directed Immunoconjugate
CHEBI has role CHEBI:35610 antineoplastic agent

Related Drugs by ATC class:

L01FB CD22 (Clusters of Differentiation 22) inhibitors 1 drug
moxetumomab pasudotox

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

DiseaseRelationSNOMED_IDDOID
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:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
B-cell receptor CD22 Membrane receptor ANTIBODY BINDING Kd 9.70 IUPHAR DRUG LABEL

External reference:

IDSource
P93RUU11P7 UNII
4036877 VANDF
C1567130 UMLSCUI
CHEBI:753564 CHEBI
CHEMBL2108611 ChEMBL_ID
DB05889 DRUGBANK_ID
D08933 KEGG_DRUG
CHEMBL4297558 ChEMBL_ID
D000080045 MESH_DESCRIPTOR_UI
8574 INN_ID
8266 IUPHAR_LIGAND_ID
736495009 SNOMEDCT_US
763600004 SNOMEDCT_US
261074 MMSL
33023 MMSL
d08638 MMSL
017318 NDDF
1942950 RXNORM

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Besponsa HUMAN PRESCRIPTION DRUG LABEL 1 0008-0100 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 0.25 mg INTRAVENOUS BLA 28 sections