Identification

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Name
Mogamulizumab
Accession Number
DB12498
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Description

Mogamulizumab is a humanized monoclonal antibody (mAb) directed against CC chemokine receptor 4 (CCR4) for the treatment of Mycosis Fungoides (MF) and Sézary Syndrome (SS), the most common subtypes of cutaneous T-cell lymphoma. Cutaneous T-cell lymphomas occur when certain white blood cells, called T cells, become cancerous; these cancers typically affect the skin, causing various types of skin lesions 8.

On August 8 2018, the U.S. Food and Drug Administration (FDA) approved mogamulizumab injection (also known as Poteligeo) for intravenous use for the treatment of adult patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after at least one prior systemic therapy 7.

Mogamulizumab is derived from Kyowa Hakko Kirin's POTELLIGENT (®) technology, which produces antibodies with enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) activity. Approval in Japan was granted on April 30 2012 by the Japanese Ministry of Health, Labour and Welfare for patients with relapsed or refractory CCR4-positive adult T-cell leukemia-lymphoma 2.

Protein chemical formula
Not Available
Protein average weight
Not Available
Sequences
Not Available
Synonyms
  • mogamulizumab-kpkc
External IDs
AMG-761 / KM-8761 / KM8761 / KW 0761 / KW-0761
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PoteligeoInjection4 mg/1mLIntravenousKyowa Kirin, Inc.2018-08-08Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories
UNII
YI437801BE
CAS number
1159266-37-1

Pharmacology

Indication

For the intravenous use for the treatment of adult patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after at least one prior systemic therapy. This approval provides a new treatment option for patients with MF and is the first FDA approval of a drug specifically for Sézary Syndrome Label.

Pharmacodynamics

This drug is a CC chemokine receptor 4 (CCR4) antagonist. It is a monoclonal antibody which blocks T cell proliferation, which leads to malignancy 1, 6. CCR4 is a chemokine receptor that is preferentially expressed by Th2 and regulatory T (Treg) cells. In response to its ligands, CCL17 (TARC) and CCL22 (MDC), CCR4 promotes T-cell migration to extranodal sites, including the skin 6.

Mechanism of action

Mogamulizumab selectively binds to and inhibits the activity of CCR4, which may block CCR4-mediated signal transduction pathways and, so, chemokine-mediated cellular migration and proliferation of T cells, as well as chemokine-mediated angiogenesis. Additionally, this agent may induce antibody-dependent cell-mediated cytotoxicity (ADCC) against CCR4-positive T cells. CCR4, a G-coupled-protein receptor for C-C chemokines such MIP-1, RANTES, TARC and MCP-1, is expressed on the surfaces of some types of T cells, endothelial cells, and certain types of neurons. CCR4, also known as CD194, may be overexpressed on adult T-cell lymphoma (ATL) and peripheral T-cell lymphoma (PTCL) cells 10. In addition to directly targeting malignant T cells expressing CCR4, mogamulizumab depletes Treg cells, an important therapeutic target in many human cancers because of their role in suppressing host antitumor immunity 6.

TargetActionsOrganism
AC-X-C chemokine receptor type 4
antagonist
Humans
Additional Data Available
Adverse Effects

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Blackbox Warnings

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Absorption

Following repeated dosing of the approved recommended dosage, steady-state concentrations were reached after 8 doses (12 weeks), and the systemic accumulation was 1.6-fold. At steady state, the peak concentration (Cmax,ss) is 32 (68%) μg/mL, the trough concentration (Cmin,ss) is 11 (239%) μg/mL, and AUCss is 5577 (125%) μg•hr/mL Label.

Volume of distribution

The central volume of distribution is 3.6 L Label.

Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

The terminal half-life is 17 days Label.

Clearance

Clearance is 12 mL/h Label.

Toxicity

The most common adverse reactions (reported in ≥20% of patients randomized to mogamulizumab) were rash (including drug eruption), infusion-related reactions, fatigue, diarrhea, upper respiratory tract infection and musculoskeletal pain Label. Due to various adverse effects related to this drug, the adverse reactions have been categorized by organ system. Because of the risk of serious/fatal ADRs, patients administered mogamulizumab should be carefully monitored 3.

Upper respiratory tract infection: This may occur due to decreased immunity following the administration of this drug. Monitor for signs of respiratory infection including fever, cough and shortness of breath 9.

Dermatological: Patients must contact their healthcare provider immediately if they experience a new or worsening skin rash. Treatment should be temporarily interrupted for moderate or severe skin rashes and permanently discontinued for a life-threatening rash. Fatal and life-threatening skin adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have occurred in recipients of mogamulizumab. Rash (drug eruption) is one of the most common adverse reactions associated with mogamulizumab 9, Label.

Infusion Reactions: Patients must contact their healthcare provider immediately for signs or symptoms of infusion reactions. Treatment should be suspended for any infusion reaction and permanently discontinued for any life-threatening infusion reaction 9.

Infections: Patients must contact their healthcare provider if they experience fever or other signs of infection. Infections should be monitored and treated promptly 9.

Autoimmune Complications: Immune-mediated or possibly immune-mediated reactions have included myositis, myocarditis, polymyositis, hepatitis, pneumonitis, and a variant of Guillain- Barré syndrome Label. Patients must notify their healthcare provider of any history of autoimmune disease. Treatment should be suspended or permanently discontinued as appropriate 9. Fatal and life-threatening immune-mediated complications have been reported in recipients of this drug Label.

Musculoskeletal pain: This drug may cause musculoskeletal pain Label

A note on complications of allogeneic hematopoietic stem cell transplantation: Patients must be aware of the possible risk of post-transplant complications when taking this agent. Patients should be monitored for severe acute graft-versus-host disease (GVHD) and steroid-refractory GVHD.

Females of Reproductive Potential: Females who are able to become pregnant should use an effective method of birth control during treatment with Poteligeo and for at least three months after the last dose 9.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
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.
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Mogamulizumab.
AbituzumabThe risk or severity of adverse effects can be increased when Mogamulizumab is combined with Abituzumab.
AbrilumabThe risk or severity of adverse effects can be increased when Mogamulizumab is combined with Abrilumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Mogamulizumab.
AdecatumumabThe risk or severity of adverse effects can be increased when Adecatumumab is combined with Mogamulizumab.
AducanumabThe risk or severity of adverse effects can be increased when Aducanumab is combined with Mogamulizumab.
AfelimomabThe risk or severity of adverse effects can be increased when Afelimomab is combined with Mogamulizumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Mogamulizumab.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Mogamulizumab.
AmatuximabThe risk or severity of adverse effects can be increased when Mogamulizumab is combined with Amatuximab.
Additional Data Available
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  • Severity
    Severity

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  • Evidence Level
    Evidence Level

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  • Action
    Action

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Food Interactions
Not Available

References

General References
  1. Makita S, Tobinai K: Mogamulizumab for the treatment of T-cell lymphoma. Expert Opin Biol Ther. 2017 Sep;17(9):1145-1153. doi: 10.1080/14712598.2017.1347634. Epub 2017 Jul 3. [PubMed:28649848]
  2. Beck A, Reichert JM: Marketing approval of mogamulizumab: a triumph for glyco-engineering. MAbs. 2012 Jul-Aug;4(4):419-25. doi: 10.4161/mabs.20996. Epub 2012 Jul 1. [PubMed:22699226]
  3. Ishitsuka K, Yurimoto S, Kawamura K, Tsuji Y, Iwabuchi M, Takahashi T, Tobinai K: Safety and efficacy of mogamulizumab in patients with adult T-cell leukemia-lymphoma in Japan: interim results of postmarketing all-case surveillance. Int J Hematol. 2017 Oct;106(4):522-532. doi: 10.1007/s12185-017-2270-9. Epub 2017 Jun 9. [PubMed:28597329]
  4. Sato T, Coler-Reilly ALG, Yagishita N, Araya N, Inoue E, Furuta R, Watanabe T, Uchimaru K, Matsuoka M, Matsumoto N, Hasegawa Y, Yamano Y: Mogamulizumab (Anti-CCR4) in HTLV-1-Associated Myelopathy. N Engl J Med. 2018 Feb 8;378(6):529-538. doi: 10.1056/NEJMoa1704827. [PubMed:29414279]
  5. Ni X, Jorgensen JL, Goswami M, Challagundla P, Decker WK, Kim YH, Duvic MA: Reduction of regulatory T cells by Mogamulizumab, a defucosylated anti-CC chemokine receptor 4 antibody, in patients with aggressive/refractory mycosis fungoides and Sezary syndrome. Clin Cancer Res. 2015 Jan 15;21(2):274-85. doi: 10.1158/1078-0432.CCR-14-0830. Epub 2014 Nov 5. [PubMed:25376389]
  6. Wilcox RA: Mogamulizumab: 2 birds, 1 stone. Blood. 2015 Mar 19;125(12):1847-8. doi: 10.1182/blood-2015-02-625251. [PubMed:25792728]
  7. FDA approves treatment for two rare types of non-Hodgkin lymphoma [Link]
  8. Sezary Syndrome [Link]
  9. POTELIGEO [Link]
  10. Mogamulizumab NCI [Link]
External Links
PubChem Substance
347911339
Wikipedia
Mogamulizumab
ATC Codes
L01XC25 — Mogamulizumab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentTumors, Solid1
1CompletedTreatmentAdult Peripheral T-Cell Lymphoma (PTCL) / Adult T-Cell Leukemia and Lymphoma (ATL)1
1CompletedTreatmentAdvanced Solid Tumors1
1CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1CompletedTreatmentTumors, Solid1
1Not Yet RecruitingTreatmentAdult T-Cell Lymphoma/Leukemia / Mycosis Fungoides (MF) / Sezary Syndrome1
1RecruitingTreatmentCarcinoma NOS / Malignancies / Tumors, Solid1
1RecruitingTreatmentEsophageal Cancers / Lung Cancers / Malignant Neoplasm of Stomach / Oral Cancers / Renal Cancers1
1TerminatedBasic ScienceAsthma1
1TerminatedTreatmentAdvanced/Metastatic Solid Tumors1
1, 2CompletedTreatmentCarcinoma NOS / HCC / Hepatocellular,Carcinoma / Malignancies / Tumors, Solid1
1, 2CompletedTreatmentPeripheral T-Cell Lymphoma (PTCL)1
1, 2RecruitingTreatmentAdvanced Solid Tumors / Metastatic Solid Tumors1
1, 2RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL) / Recurrent Diffuse Large B-Cell Lymphoma / Recurrent High Grade B-Cell Lymphoma / Recurrent Hodgkin Lymphoma / Recurrent Non-Hodgkin Lymphoma / Recurrent Transformed B-cell Non-Hodgkin Lymphoma / Refractory Diffuse Large B Cell Lymphoma / Refractory High Grade B-Cell Lymphoma / Refractory Hodgkin Lymphoma / Refractory Non-Hodgkin's lymphoma / Refractory Transformed B-cell Non-Hodgkin Lymphoma1
2CompletedTreatmentAdult T-cell lymphomas/leukaemias3
2CompletedTreatmentCutaneous T-Cell Lymphoma (CTCL) / Peripheral T-Cell Lymphoma (PTCL)1
2CompletedTreatmentPeripheral T-Cell Lymphoma (PTCL)1
2CompletedTreatmentPeripheral T/NK-cell Lymphoma1
2Not Yet RecruitingTreatmentStage IB-IIB Cutaneous T-Cell Lymphoma1
3Active Not RecruitingTreatmentCutaneous T-Cell Lymphoma (CTCL)1
3Active Not RecruitingTreatmentHTLV-1 Associated Myelopathy1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
InjectionIntravenous4 mg/1mL
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available

Taxonomy

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

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Virus receptor activity
Specific Function
Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Acts as a receptor for extracellular ubiq...
Gene Name
CXCR4
Uniprot ID
P61073
Uniprot Name
C-X-C chemokine receptor type 4
Molecular Weight
39745.055 Da
References
  1. Makita S, Tobinai K: Mogamulizumab for the treatment of T-cell lymphoma. Expert Opin Biol Ther. 2017 Sep;17(9):1145-1153. doi: 10.1080/14712598.2017.1347634. Epub 2017 Jul 3. [PubMed:28649848]
  2. Beck A, Reichert JM: Marketing approval of mogamulizumab: a triumph for glyco-engineering. MAbs. 2012 Jul-Aug;4(4):419-25. doi: 10.4161/mabs.20996. Epub 2012 Jul 1. [PubMed:22699226]
  3. Ishitsuka K, Yurimoto S, Kawamura K, Tsuji Y, Iwabuchi M, Takahashi T, Tobinai K: Safety and efficacy of mogamulizumab in patients with adult T-cell leukemia-lymphoma in Japan: interim results of postmarketing all-case surveillance. Int J Hematol. 2017 Oct;106(4):522-532. doi: 10.1007/s12185-017-2270-9. Epub 2017 Jun 9. [PubMed:28597329]
  4. Wilcox RA: Mogamulizumab: 2 birds, 1 stone. Blood. 2015 Mar 19;125(12):1847-8. doi: 10.1182/blood-2015-02-625251. [PubMed:25792728]

Drug created on October 20, 2016 16:38 / Updated on December 02, 2019 09:26