Identification
- Summary
Gemtuzumab ozogamicin is a monoclonal anti-CD33 antibody used to treat CD33-positive acute myeloid leukemia.
- Brand Names
- Mylotarg
- Generic Name
- Gemtuzumab ozogamicin
- DrugBank Accession Number
- DB00056
- Background
Gemtuzumab ozogamicin is a recombinant humanized IgG4 kappa antibody which is conjugated with calicheamicin derivative, a cytotoxic antitumor antibiotic isolated from fermentation of Micromonospora echinospora ssp. calichensis. Gemtuzumab ozogamicin has approximately 50% of the antibody loaded with 4-6 moles calicheamicin per mole of antibody Label. The antibody is specifically directed against the CD33 antigen present on leukemic myeloblasts in most patients with acute myeloid leukemia (AML). By binding to the CD33 antigen on tumors, the cytotoxic agent blocks the growth of cancerous cells and causes cell death.
Marketing approval of gemtuzumab ozogamicin was granted on May 17, 2000 by FDA as a treatment for patients with CD33-positive AML in first relapse who are 60 years of age or older and who are not considered candidates for cytotoxic chemotherapy 1. However, it was voluntarily withdrawn from the market in 2010 due to safety concerns, increased patient deaths and insufficient evidence of clinical benefit during confirmatory trials 5. On September 1 2017, gemtuzumab ozogamicin was again approved for the treatment of adults with newly diagnosed CD33-positive acute myeloid leukemia but with a lower dosing regimen and a different schedule in combination with chemotherapy or on its own 5. It is also indicated for the treatment of patients aged 2 years and older with CD33-positive AML who have experienced a relapse or who have not responded to initial treatment (refractory) 5.
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Structure
- Protein Chemical Formula
- Not Available
- Protein Average Weight
- 151500.0 Da (range)
- Sequences
>Light Chain DIQLTQSPSTLSASVGDRVTITCRASESLDNYGIRFLTWFQQKPGKAPKLLMYAASNQGS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQTKEVPWSFGQGTKVEVKRTVAAPSVF IFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLS STLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
>Heavy Chain EVQLVQSGAEVKKPGSSVKVSCKASGYTITDSNIHWVRQAPGQSLEWIGYIYPYNGGTDY NQKFKNRATLTVDNPTNTAYMELSSLRSEDTAFYYCVNGNPWLAYWGQGTLVTVSSASTK GPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS LSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFP PKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVS VLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFS CSVMHEALHNHYTQKSLSLSLGK
Download FASTA Format- Synonyms
- Gemtuzumab ozogamicin
Pharmacology
- Indication
Indicated for the treatment of patients with CD33 positive acute myeloid leukemia in first relapse who are 60 years of age or older and who are not considered candidates for other cytotoxic chemotherapy. Indicated for the treatment of patients aged 2 years and older with CD33-positive AML who have experienced a relapse or who have not responded to initial treatment (refractory).
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Acute myeloid leukemia •••••••••••• ••••••••••• •••••• ••••••• ••••••••• ••••• ••••••••• ••••••••• Treatment of Refractory acute myeloid leukemia •••••••••••• ••••••••••• •••••• ••••••• ••••••••• ••••••••• Treatment of Relapsed acute myeloid leukemia •••••••••••• ••••••••••• •••••• ••••••••• ••••••••• - Contraindications & Blackbox Warnings
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Used for the treatment of acute myeloid leukemia (AML), mylotarg binds to the CD33 antigen, which is expressed on the surface of leukemic cells in more than 80% of patients with AML. The CD33 antigen is not expressed on pluripotent hematopoietic stem cells or nonhematopoietic cells. This gives mylotarg the selectivity needed to target leukemic cells.
- Mechanism of action
Mylotarg is directed against the CD33 antigen expressed by hematopoietic cells. Binding of the anti-CD33 antibody portion of Mylotarg with the CD33 antigen results in the formation of a complex that is internalized. Upon internalization, the calicheamicin derivative is released inside the lysosomes of the myeloid cell. The released calicheamicin derivative binds to DNA in the minor groove resulting in site-specific DNA double strand breaks via formation of a p-benzene diradical 4. Eventually, cell death is induced.
Target Actions Organism AMyeloid cell surface antigen CD33 antibodyregulatorHumans ULow affinity immunoglobulin gamma Fc region receptor III-B Not Available Humans ULow affinity immunoglobulin gamma Fc region receptor III-A Not Available Humans UHigh affinity immunoglobulin gamma Fc receptor I Not Available Humans - Absorption
In pediatric patients receiving a dose level of 9mg/m^2, the peak plasma concentration (Cmax) was approximately 3.47±1.04 mg/L with the AUC of 136 ±107 mg * h/L 4.
- Volume of distribution
The volume of distribution at steady state (Vss) was approximately 6.5 ± 5.5 L in pediatric patients receiving a dose level of 9mg/m^2 4.
- Protein binding
Not Available
- Metabolism
Metabolic studies indicate hydrolytic release of the calicheamicin derivative from gemtuzumab ozogamicin. The drug is most likely removed by opsonization via the reticuloendothelial system.
- Route of elimination
Not Available
- Half-life
In pediatric patients receiving a dose level of 9mg/m^2, the half life was approximately 64±44 h after the first dose 4.
- Clearance
The mean clearance rate was approximately 0.12±0.15 L/h/m^2 in pediatric patients receiving a dose level of 9mg/m^2 4.
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
The most frequently reported toxicities are myelosuppression and hepatic veno-occlusive disorder.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- 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 Integrate drug-drug
interactions in your softwareAbatacept The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Gemtuzumab ozogamicin. Acenocoumarol The risk or severity of bleeding can be increased when Acenocoumarol is combined with Gemtuzumab ozogamicin. Acetylsalicylic acid The risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Gemtuzumab ozogamicin. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Gemtuzumab ozogamicin. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Mylotarg Injection, powder, for solution 5 mg Intravenous Pfizer Europe Ma Eeig 2020-12-22 Not applicable EU 
Mylotarg Powder, for solution 4.5 mg / vial Intravenous Pfizer Canada Ulc 2020-03-11 Not applicable Canada 
Mylotarg Injection, powder, lyophilized, for solution 5 mg/5mL Intravenous Wyeth Pharmaceuticals Llc, a Subsidiary of Pfizer Inc. 2017-09-07 Not applicable US 
Categories
- ATC Codes
- L01FX02 — Gemtuzumab ozogamicin
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antibody-drug Conjugates
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Antineoplastic and Immunomodulating Agents
- Blood Proteins
- Calicheamicins
- Cancer immunotherapy
- Carbohydrates
- CD33-directed Antibody Interactions
- CD33-directed Cytotoxin
- Globulins
- Glycosides
- Hepatotoxic Agents
- Immunoconjugates
- Immunoglobulins
- Immunologic Factors
- Immunoproteins
- Immunosuppressive Agents
- Immunotherapy
- Immunotoxins
- MONOCLONAL ANTIBODIES AND ANTIBODY DRUG CONJUGATES
- Myelosuppressive Agents
- Narrow Therapeutic Index Drugs
- Noxae
- Proteins
- Serum Globulins
- Toxic Actions
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 8GZG754X6M
- CAS number
- 220578-59-6
References
- General References
- Bross PF, Beitz J, Chen G, Chen XH, Duffy E, Kieffer L, Roy S, Sridhara R, Rahman A, Williams G, Pazdur R: Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. Clin Cancer Res. 2001 Jun;7(6):1490-6. [Article]
- Giles FJ, Kantarjian HM, Kornblau SM, Thomas DA, Garcia-Manero G, Waddelow TA, David CL, Phan AT, Colburn DE, Rashid A, Estey EH: Mylotarg (gemtuzumab ozogamicin) therapy is associated with hepatic venoocclusive disease in patients who have not received stem cell transplantation. Cancer. 2001 Jul 15;92(2):406-13. [Article]
- Wadleigh M, Richardson PG, Zahrieh D, Lee SJ, Cutler C, Ho V, Alyea EP, Antin JH, Stone RM, Soiffer RJ, DeAngelo DJ: Prior gemtuzumab ozogamicin exposure significantly increases the risk of veno-occlusive disease in patients who undergo myeloablative allogeneic stem cell transplantation. Blood. 2003 Sep 1;102(5):1578-82. Epub 2003 May 8. [Article]
- Buckwalter M, Dowell JA, Korth-Bradley J, Gorovits B, Mayer PR: Pharmacokinetics of gemtuzumab ozogamicin as a single-agent treatment of pediatric patients with refractory or relapsed acute myeloid leukemia. J Clin Pharmacol. 2004 Aug;44(8):873-80. [Article]
- FDA Press Announcements: FDA approves Mylotarg for treatment of acute myeloid leukemia [Link]
- External Links
- PubChem Substance
- 46505767
- 1294580
- ChEMBL
- CHEMBL1201506
- Therapeutic Targets Database
- DAP000390
- PharmGKB
- PA164749431
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Gemtuzumab_ozogamicin
- FDA label
- Download (160 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 Completed Treatment Acute Myeloid Leukemia 1 4 Completed Treatment Acute Myeloid Leukemia / Intravenous Infusions 1 4 Completed Treatment ECG / Pharmacokinetics / Safety 1 3 Completed Treatment Acute Myeloid Leukemia 6 3 Completed Treatment Leukemias 4
Pharmacoeconomics
- Manufacturers
- Wyeth pharmaceuticals inc
- Packagers
- Ben Venue Laboratories Inc.
- Wyeth Pharmaceuticals
- Dosage Forms
Form Route Strength Injection, powder, for solution Intravenous 5 MG Injection, powder, lyophilized, for solution Intravenous 5 mg/5mL Powder, for solution Intravenous 4.5 mg / vial Powder, for solution Intravenous 5.0 mg - Prices
Unit description Cost Unit Mylotarg 5 mg vial 3104.82USD vial DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5773001 No 1998-06-30 2015-06-30 US US5585089 No 1996-12-17 2013-12-17 US
Properties
- State
- Liquid
- Experimental Properties
Property Value Source melting point (°C) 61 °C (FAB fragment), 71 °C (whole mAb) Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntibodyRegulator
- General Function
- Receptor activity
- Specific Function
- Putative adhesion molecule of myelomonocytic-derived cells that mediates sialic-acid dependent binding to cells. Preferentially binds to alpha-2,6-linked sialic acid. The sialic acid recognition si...
- Gene Name
- CD33
- Uniprot ID
- P20138
- Uniprot Name
- Myeloid cell surface antigen CD33
- Molecular Weight
- 39824.885 Da
References
- Naito K, Takeshita A, Shigeno K, Nakamura S, Fujisawa S, Shinjo K, Yoshida H, Ohnishi K, Mori M, Terakawa S, Ohno R: Calicheamicin-conjugated humanized anti-CD33 monoclonal antibody (gemtuzumab zogamicin, CMA-676) shows cytocidal effect on CD33-positive leukemia cell lines, but is inactive on P-glycoprotein-expressing sublines. Leukemia. 2000 Aug;14(8):1436-43. [Article]
- Niculescu-Duvaz I: Technology evaluation: gemtuzumab ozogamicin, Celltech Group. Curr Opin Mol Ther. 2000 Dec;2(6):691-6. [Article]
- van Der Velden VH, te Marvelde JG, Hoogeveen PG, Bernstein ID, Houtsmuller AB, Berger MS, van Dongen JJ: Targeting of the CD33-calicheamicin immunoconjugate Mylotarg (CMA-676) in acute myeloid leukemia: in vivo and in vitro saturation and internalization by leukemic and normal myeloid cells. Blood. 2001 May 15;97(10):3197-204. [Article]
- Bross PF, Beitz J, Chen G, Chen XH, Duffy E, Kieffer L, Roy S, Sridhara R, Rahman A, Williams G, Pazdur R: Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. Clin Cancer Res. 2001 Jun;7(6):1490-6. [Article]
- Sievers EL, Larson RA, Stadtmauer EA, Estey E, Lowenberg B, Dombret H, Karanes C, Theobald M, Bennett JM, Sherman ML, Berger MS, Eten CB, Loken MR, van Dongen JJ, Bernstein ID, Appelbaum FR: Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. J Clin Oncol. 2001 Jul 1;19(13):3244-54. [Article]
- McHayleh W, Foon K, Redner R, Sehgal R, Raptis A, Agha M, Luong TM, Schlesselman JJ, Boyiadzis M: Gemtuzumab ozogamicin as first-line treatment in patients aged 70 years or older with acute myeloid leukemia. Cancer. 2010 Jun 15;116(12):3001-5. doi: 10.1002/cncr.25078. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kyriakidis I, Vasileiou E, Rossig C, Roilides E, Groll AH, Tragiannidis A: Invasive Fungal Diseases in Children with Hematological Malignancies Treated with Therapies That Target Cell Surface Antigens: Monoclonal Antibodies, Immune Checkpoint Inhibitors and CAR T-Cell Therapies. J Fungi (Basel). 2021 Mar 5;7(3). pii: jof7030186. doi: 10.3390/jof7030186. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Not Available
- Specific Function
- Receptor for the Fc region of immunoglobulins gamma. Low affinity receptor. Binds complexed or aggregated IgG and also monomeric IgG. Contrary to III-A, is not capable to mediate antibody-dependent...
- Gene Name
- FCGR3B
- Uniprot ID
- O75015
- Uniprot Name
- Low affinity immunoglobulin gamma Fc region receptor III-B
- Molecular Weight
- 26215.64 Da
References
- Caron PC, Lai LT, Scheinberg DA: Interleukin-2 enhancement of cytotoxicity by humanized monoclonal antibody M195 (anti-CD33) in myelogenous leukemia. Clin Cancer Res. 1995 Jan;1(1):63-70. [Article]
- Rogler G, Hausmann M, Vogl D, Aschenbrenner E, Andus T, Falk W, Andreesen R, Scholmerich J, Gross V: Isolation and phenotypic characterization of colonic macrophages. Clin Exp Immunol. 1998 May;112(2):205-15. [Article]
- Ericson SG, Benoit NE, Mills LE, Fanger MW: The effect of recombinant human interleukin-3 and recombinant human granulocyte-macrophage colony-stimulating factor on Fc gamma receptor expression and antibody-dependent cellular cytotoxicity of hematopoietic progenitor cells during in vitro myeloid maturation. Exp Hematol. 1994 Mar;22(3):283-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
- Ericson SG, Benoit NE, Mills LE, Fanger MW: The effect of recombinant human interleukin-3 and recombinant human granulocyte-macrophage colony-stimulating factor on Fc gamma receptor expression and antibody-dependent cellular cytotoxicity of hematopoietic progenitor cells during in vitro myeloid maturation. Exp Hematol. 1994 Mar;22(3):283-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Receptor signaling protein activity
- Specific Function
- High affinity receptor for the Fc region of immunoglobulins gamma. Functions in both innate and adaptive immune responses.
- Gene Name
- FCGR1A
- Uniprot ID
- P12314
- Uniprot Name
- High affinity immunoglobulin gamma Fc receptor I
- Molecular Weight
- 42631.525 Da
References
- Ericson SG, Benoit NE, Mills LE, Fanger MW: The effect of recombinant human interleukin-3 and recombinant human granulocyte-macrophage colony-stimulating factor on Fc gamma receptor expression and antibody-dependent cellular cytotoxicity of hematopoietic progenitor cells during in vitro myeloid maturation. Exp Hematol. 1994 Mar;22(3):283-9. [Article]
Drug created at June 13, 2005 13:24 / Updated at January 02, 2024 23:41