Inotuzumab ozogamicin
Accession Number
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)

Inotuzumab ozogamicin is an antibody-drug conjugate using linker and cytotoxic drug technology similar to that developed for the ground-breaking treatment Mylotarg (Gemtuzumab ozogamicin), which was approved by the US FDA in 2000 for the treatment of acute myeloid leukaemia. Inotuzumab ozogamicin consists of a recombinant humanised IgG4 kappa CD22-targeting monoclonal antibody covalently attached to calicheamicin derivative, N-acetyl-gamma-calicheamicin dimethylhydrazide, which is a potent DNA-binding cytotoxic agent [4]. Developed by Pfizer and UCB, inotuzumab ozogamicin was granted approval by EU in June 2017 followed by FDA on August 17th, 2017 for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). ALL is a rapidly progressing cancer of the bone marrow that is associated with high mortality rates and low therapeutic response from standard chemotherapies in relasping conditions. In a randomized trial, inotuzumab ozogamicin displayed higher percentages of patients undergoing longer periods of complete remission with no evidence of disease in comparison to patients receiving alternative chemotherapy [5].

Protein structure
Protein chemical formula
Not Available
Protein average weight
Not Available
Not Available
Not Available
External IDs
CMC 544 / CMC-544 / PF-05208773 / WAY-207294
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BesponsaInjection, powder, lyophilized, for solution0.25 mg/1mLIntravenousWyeth Pharmaceuticals Llc, a Subsidiary of Pfizer Inc.2017-08-18Not applicableUs
BesponsaPowder, for solution0.9 mgIntravenousPfizerNot applicableNot applicableCanada
CAS number



Indicated as monotherapy for the treatment of adults with relapsed or refractory CD22-positive B cell precursor acute lymphoblastic leukaemia (ALL).

Associated Conditions

Inotuzumab ozogamicin is an antineoplastic agent that targets CD22 antigen expressed on immature B-cell lymphocytes and blocks further growth of tumor cells. The drug aims to restore normal blood counts and achieve complete remission from the disease. QT interval prolongation was observed in patients receiving inotuzumab ozogamicin.

Mechanism of action

Inotuzumab ozogamicin is comprised of cytotoxic antibiotic N-acetyl-gamma-calicheamicin dimethylhydrazide attached to a humanized monoclonal IgG4 antibody via 4-(4 acetylphenoxy) butanoic acid (acetyl butyrate) linker. The drug exerts a potent cytotoxic effect against CD22+ B-cell lymphoma when the antibody binds to the CD22 receptor on the surface of B cells . The drug-CD22 complex is rapidly internalized into the cell, forming an endosome which subsequently fuses with lysosomes. N-acetyl-gamma-calicheamicin dimethylhydrazide is then intracellularly released into the acidic environment. N-acetyl-gamma-calicheamicin dimethylhydrazide is a calicheamicin derivative, which is naturally produced by the bacterium Micromonospora echinospora, and is toxic to the body when not bound to the antibody. It mediates apoptosis of the cell by binding to the minor groove of DNA in a sequence-specific manner and undergoing a structural change to generate diradicals [A20354]. These changes abstract hydrogen ions from the phosphodiester bonds of double-stranded DNA, resulting in breaks and cell apoptosis [1, 2, 4].

AB-cell receptor CD22

Inotuzumab ozogamicin is intended to be administered in cycles that each run for 3 to 4 weeks. The steady state exposure of the drug is reached by Cycle 4. The mean (SD) maximum serum concentration (Cmax) of inotuzumab ozogamicin was 308 ng/mL (362) with patients receving the recommended dose of 1.8 mg/m^2/cycle [6].

Volume of distribution

The total volume of distribution of inotuzumab ozogamicin is approximately 12L [6].

Protein binding

In vitro studies show the binding of the N-acetyl-gamma-calicheamicin dimethylhydrazide to human plasma proteins to be approximately 97% [6].


N-acetyl-gamma-calicheamicin dimethylhydrazide primarily undergoes nonenzymatic reduction in vitro. The metabolism of N-acetyl-gamma-calicheamicin dimethylhydrazide in human serum is not clearly understood as the level of the drug is below the limit of quantification of 50 pg/mL [6]. The antibody portion of the drug is thought to undergo proteolytic degradation into amino acids then recycled into other proteins [3].

Route of elimination

The drug is disposited in the body after administration.

Half life

The elimination half life at the end of Cycle 4 of administration is approximately 12.3 days in a 2-compartment model [6].


The clearance of inotuzumab ozogamicin at steady state is 0.0333 L/h [6].


Inotuzumab ozogamicin was shown to be clastogenic in vivo in the bone marrow of male mice but was not mutagenic in an* in vitro* bacterial reverse mutation (Ames) assay. In rat toxicity studies, rats developed oval cell hyperplasia, altered hepatocellular foci, and hepatocellular adenomas however the carcinogenic potential of inotuzumab ozogamicin on humans is undetermined. Based on reproductive toxicity studies involving female rats and non-clinical studies, inotuzumab ozogamicin has the potential to impair reproductive function and fertility in men and women [6].

Affected organisms
  • Humans and other mammals
Not Available
Pharmacogenomic Effects/ADRs
Not Available


Drug Interactions
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Inotuzumab ozogamicin.
AbemaciclibThe serum concentration of Inotuzumab ozogamicin can be increased when it is combined with Abemaciclib.
AbituzumabThe risk or severity of adverse effects can be increased when Inotuzumab ozogamicin is combined with Abituzumab.
AcebutololThe serum concentration of Inotuzumab ozogamicin can be increased when it is combined with Acebutolol.
AcetaminophenThe serum concentration of Inotuzumab ozogamicin can be increased when it is combined with Acetaminophen.
Acetylsalicylic acidThe serum concentration of Inotuzumab ozogamicin can be increased when it is combined with Acetylsalicylic acid.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Inotuzumab ozogamicin.
AdecatumumabThe risk or severity of adverse effects can be increased when Adecatumumab is combined with Inotuzumab ozogamicin.
AducanumabThe risk or severity of adverse effects can be increased when Inotuzumab ozogamicin is combined with Aducanumab.
AfatinibThe serum concentration of Inotuzumab ozogamicin can be increased when it is combined with Afatinib.
Food Interactions
Not Available


General References
  1. DiJoseph JF, Goad ME, Dougher MM, Boghaert ER, Kunz A, Hamann PR, Damle NK: Potent and specific antitumor efficacy of CMC-544, a CD22-targeted immunoconjugate of calicheamicin, against systemically disseminated B-cell lymphoma. Clin Cancer Res. 2004 Dec 15;10(24):8620-9. [PubMed:15623646]
  2. Dijoseph JF, Dougher MM, Armellino DC, Evans DY, Damle NK: Therapeutic potential of CD22-specific antibody-targeted chemotherapy using inotuzumab ozogamicin (CMC-544) for the treatment of acute lymphoblastic leukemia. Leukemia. 2007 Nov;21(11):2240-5. Epub 2007 Jul 26. [PubMed:17657218]
  3. Han TH, Zhao B: Absorption, distribution, metabolism, and excretion considerations for the development of antibody-drug conjugates. Drug Metab Dispos. 2014 Nov;42(11):1914-20. doi: 10.1124/dmd.114.058586. Epub 2014 Jul 21. [PubMed:25048520]
  4. Yilmaz M, Richard S, Jabbour E: The clinical potential of inotuzumab ozogamicin in relapsed and refractory acute lymphocytic leukemia. Ther Adv Hematol. 2015 Oct;6(5):253-61. doi: 10.1177/2040620715596715. [PubMed:26425338]
  5. Kantarjian HM, DeAngelo DJ, Stelljes M, Martinelli G, Liedtke M, Stock W, Gokbuget N, O'Brien S, Wang K, Wang T, Paccagnella ML, Sleight B, Vandendries E, Advani AS: Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia. N Engl J Med. 2016 Aug 25;375(8):740-53. doi: 10.1056/NEJMoa1509277. Epub 2016 Jun 12. [PubMed:27292104]
  6. European Medicines Agency (EMA): BESPONSA Summary of Product Characteristics [Link]
External Links
PubChem Substance
AHFS Codes
  • 10:00.00 — Antineoplastic Agents

Clinical Trials

Clinical Trials
1CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL)1
1CompletedTreatmentLymphoma, B-Cell4
1CompletedTreatmentRefractory Follicular Lymphoma1
1RecruitingTreatmentAcute Leukemias of Ambiguous Lineage / B-cell Adult Acute Lymphoblastic Leukemia / Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Adult Burkitt Lymphoma1
1, 2Active Not RecruitingTreatmentAcute Lymphocytic Leukemia (ALL)1
1, 2CompletedTreatmentLymphoma, B-Cell1
1, 2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative / Leukemias / Untreated Adult Acute Lymphoblastic Leukemia1
1, 2RecruitingTreatmentCD22-positive Acute Lymphoblastic Leukemia / Cluster of Differentiation Antigen (CD22)-Positive Acute Lymphoblastic Leukemia1
1, 2RecruitingTreatmentLeukemias1
1, 2RecruitingTreatmentLeukemias / Malignant Lymphomas1
2Active Not RecruitingTreatmentChildhood B Acute Lymphoblastic Leukemia / Recurrent Childhood Acute Lymphoblastic Leukemia / Refractory Childhood Acute Lymphoblastic Leukemia1
2CompletedTreatmentLymphoma, B-Cell1
2CompletedTreatmentMalignant Lymphomas1
2Not Yet RecruitingTreatmentAcute Lymphocytic Leukemia (ALL)1
2RecruitingTreatmentAcute Lymphocytic Leukemia (ALL)2
2RecruitingTreatmentAcute Lymphocytic Leukemia (ALL) / Malignant Neoplasms Stated as Primary Lymphoid Haematopoietic1
2RecruitingTreatmentB Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative / CD22 Positive / Recurrent B Acute Lymphoblastic Leukemia / Refractory B Acute Lymphoblastic Leukemia1
2RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
2RecruitingTreatmentPrecursor Cell Lymphoblastic Leukemia1
3CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL)1
3Not Yet RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
3RecruitingTreatmentB Acute Lymphoblastic Leukemia1
3TerminatedHealth Services ResearchFollicular Lymphoma (FL)1
3TerminatedTreatmentNon-Hodgkin's Lymphoma (NHL)1
4Not Yet RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Leukemias / Precursor B-Cell Lymphoblastic Leukemia-Lymphoma1


Not Available
Not Available
Dosage forms
Injection, powder, lyophilized, for solutionIntravenous0.25 mg/1mL
Powder, for solutionIntravenous0.9 mg
Not Available
Not Available


Experimental Properties
Not Available


Not Available
Organic Compounds
Super Class
Organic Acids
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Alternative Parents
Not Available
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available


Pharmacological action
General Function
Carbohydrate binding
Specific Function
Mediates B-cell B-cell interactions. May be involved in the localization of B-cells in lymphoid tissues. Binds sialylated glycoproteins; one of which is CD45. Preferentially binds to alpha-2,6-link...
Gene Name
Uniprot ID
Uniprot Name
B-cell receptor CD22
Molecular Weight
95347.07 Da
  1. Thota S, Advani A: Inotuzumab ozogamicin in relapsed B-cell acute lymphoblastic leukemia. Eur J Haematol. 2017 May;98(5):425-434. doi: 10.1111/ejh.12862. Epub 2017 Mar 9. [PubMed:28152223]


Pharmacological action
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
Uniprot ID
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
  1. European Medicines Agency (EMA): BESPONSA Summary of Product Characteristics [Link]

Drug created on November 18, 2007 11:28 / Updated on February 13, 2019 05:18