Ibalizumab
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Identification
- Summary
Ibalizumab is a CD4-specific antibody used to treat HIV infections.
- Brand Names
- Trogarzo
- Generic Name
- Ibalizumab
- DrugBank Accession Number
- DB12698
- Background
Ibalizumab (also known as ibalizumab-uiyk and formerly known as TNX-355) is a monoclonal antibody that binds to CD4 receptors on the surface of CD4-positive cells, preventing HIV particle entry into the lymphocytes. It is an advanced and current antibody in development for the treatment of HIV/AIDS. It has been developed by Taimed biologics and Theratechnologies 8,5.
This drug was approved in March 2018 for the management of treatment-resistant HIV 5. In October 2022, the FDA approved the administration of Trogarzo (ibalizumab-uiyk) by intravenous push, allowing for a faster drug administration.11,12
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Chemical Formula
- Not Available
- Protein Average Weight
- Not Available
- Sequences
- Not Available
- Synonyms
- Ibalizumab
- Ibalizumab-uiyk
- External IDs
- TMB 355
- TMB-355
- TNX 355
- TNX-355
Pharmacology
- Indication
Indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen Label.
The approval of Trogarzo was supported by a clinical trial of 40 treatment-experienced adults with MDR HIV-1 infection who persistently had elevated levels of HIV RNA in their blood despite heavy antiretroviral therapy. The majority of study patients had previously been treated with ≥10 antiretroviral medications 5.
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 Used in combination to treat Multidrug resistant hiv-1 infection •••••••••••• ••••• ••••••• ••••••• •••••••••••••• •••••••• ••••••••• ••••••••••• ••••••••• - Contraindications & Blackbox Warnings
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- Pharmacodynamics
Trogarzo safety and effectiveness have been confirmed in a clinical trial of 40 patients who suffer multidrug-resistant HIV. The majority of these patients experienced a substantial decrease in their HIV-RNA levels within 7 days after receiving the drug. Approximately 43 percent of patients continued to experience HIV-RNA inhibition after 24 weeks of taking Trogarzo 5.
Trogarzo inhibits viral entry into cells, effectively managing HIV-1 infection in those who have attempted other therapies to no avail 5.
- Mechanism of action
Ibalizumab is a monoclonal antibody and viral-entry inhibitor that coats CD4-positive cells, the main target of HIV infection. By blocking viral entry into CD4 cells, ibalizumab creates a barrier for HIV, which is a different mechanism from those of entry inhibitors that target viral proteins or chemokine co-receptors.
Ibalizumab is a CD4 domain 2-directed post-attachment HIV-1 inhibitor. This binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to prevent viral entry into host cells without causing immunosuppression. Epitope mapping studies confirm that ibalizumab-uiyk binds to a conformational epitope located mainly in domain 2 of the extracellular region of the CD4 receptor. This epitope is located on the surface of CD4 opposite to the site in domain 1 that is essential for CD4 binding of the MHC class II molecules. This drug, therefore, does not interfere with CD4 cell-mediated immune functions. In addition, ibalizumab-uiyk does not interfere with gp120 attachment to CD4 Label. Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion 6.
CD4 is an integral cell surface glycoprotein that is able to enhance T cell-specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1).
The entry of human immunodeficiency virus (HIV) into cells requires the sequential binding of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. In addition, the CD4/gp120 interaction may directly inhibit T cell function 3.
In addition to the above mechanism of action, it was found in one study that ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4- receptor laboratory strains and primary isolates of HIV-1 in phytohemagglutinin-stimulated peripheral blood lymphocytes, further confirming its action 9.
Target Actions Organism AC-C chemokine receptor type 5 antagonistHumans AC-X-C chemokine receptor type 4 antagonistHumans AT-cell surface glycoprotein CD4 antagonistHumans - Absorption
Not Available
- Volume of distribution
4.8 L Label
- Protein binding
Not Available
- Metabolism
Metabolized by CD4 receptor internalization, ibalizumab has no significant impact on liver or kidney metabolism 10.
- Route of elimination
Not Available
- Half-life
The half-life of ibalizumab is 3 to 3.5 days on average. The half-life was estimated from a multiple-dose study evaluating weekly ibalizumab 10 mg/kg in 1 study arm and biweekly ibalizumab 25 mg/kg in another study arm, given via intravenous (IV) infusion in adults with HIV 6. In one clinical trial, the elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg (0.01 to 0.9 times the approved recommended loading dose based on a 70 kg patient) Label.
- Clearance
Following single-dose administrations of ibalizumab-uiyk as 0.5 to 1.5-hour infusions, the area under the concentration-time curve increased in a greater than dose-proportional manner, clearance decreased from 9.54 to 0.36 mL/h/kg and elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg Label.
- Adverse Effects
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- Toxicity
Immune reconstitution inflammatory syndrome has been reported in one patient treated with TROGARZO in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment Label.
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Ibalizumab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Ibalizumab. Adenovirus type 7 vaccine live The therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Ibalizumab. Aducanumab The risk or severity of adverse effects can be increased when Aducanumab is combined with Ibalizumab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Ibalizumab. - 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 Trogarzo Injection, solution, concentrate 200 mg Intravenous Theratechnologies 2021-01-28 2019-07-25 EU Trogarzo Injection, solution 150 mg/1mL Intravenous Theratechnologies 2018-04-20 Not applicable US
Categories
- ATC Codes
- J05AX23 — Ibalizumab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Anti-HIV Agents
- Anti-Infective Agents
- Anti-Retroviral Agents
- Antibodies
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antiinfectives for Systemic Use
- Antiviral Agents
- Antivirals for Systemic Use
- Blood Proteins
- CD4-directed Antibody Interactions
- CD4-directed Blocking Antibody
- Direct Acting Antivirals
- Globulins
- HIV 1 Post-attachment Fusion Inhibitors
- HIV Fusion Inhibitors
- Human Immunodeficiency Virus 1 Post-attachment Fusion Inhibitor
- Immunoglobulins
- Immunoproteins
- Proteins
- Serum Globulins
- 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
- Not Available
Chemical Identifiers
- UNII
- LT369U66CE
- CAS number
- 680188-33-4
References
- General References
- Kuritzkes DR, Jacobson J, Powderly WG, Godofsky E, DeJesus E, Haas F, Reimann KA, Larson JL, Yarbough PO, Curt V, Shanahan WR Jr: Antiretroviral activity of the anti-CD4 monoclonal antibody TNX-355 in patients infected with HIV type 1. J Infect Dis. 2004 Jan 15;189(2):286-91. Epub 2004 Jan 8. [Article]
- Vermeire K, Schols D, Bell TW: CD4 down-modulating compounds with potent anti-HIV activity. Curr Pharm Des. 2004;10(15):1795-803. [Article]
- Silberman SL, Goldman SJ, Mitchell DB, Tong AT, Rosenstein Y, Diamond DC, Finberg RW, Schreiber SL, Burakoff SJ: The interaction of CD4 with HIV-1 gp120. Semin Immunol. 1991 May;3(3):187-92. [Article]
- FDA label Trogarzo [Link]
- Trogarzo Approved to Treat Multidrug Resistant HIV-1 Infection [Link]
- Ibalizumab [Link]
- Safety, Pharmacokinetics, and Antiretroviral Activity of Multiple Doses of Ibalizumab (formerly TNX-355), an Anti-CD4 Monoclonal Antibody, in Human Immunodeficiency Virus Type 1-Infected Adults [Link]
- Ibalizumab [Link]
- Ibalizumab Targeting CD4 Receptors, An Emerging Molecule in HIV Therapy [Link]
- Monotherapy With Anti-CD4 Monoclonal Antibody Cuts Viral Load 10-Fold in 7 Days [Link]
- FDA Approved Drug Products: TROGARZO (ibalizumab-uiyk) injection, for intravenous use (October 2022) [Link]
- Globe Newswire: Theratechnologies’ Trogarzo Approved by FDA for 30-Second Intravenous (IV) Push, Simplifying HIV Treatment for Heavily Treatment-Experienced Population [Link]
- External Links
- PubChem Substance
- 347911363
- Wikipedia
- Ibalizumab
- FDA label
- Download (491 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Human Immunodeficiency Virus Type 1 (HIV-1) Infection 1 somestatus stop reason just information to hide Not Available No Longer Available Not Available Human Immunodeficiency Virus (HIV) Infections 1 somestatus stop reason just information to hide Not Available Recruiting Not Available Human Immunodeficiency Virus (HIV) Infections / Multi-Antiviral Resistance 1 somestatus stop reason just information to hide 3 Completed Treatment Human Immunodeficiency Virus (HIV) Infections 2 somestatus stop reason just information to hide 3 Completed Treatment Human Immunodeficiency Virus Type 1 (HIV-1) Infection 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Intravenous 150 mg/1mL Injection, solution, concentrate Intravenous 200 MG - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Not Available
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May play a role in the control of granulocytic lineage proliferation or differentiation. Participates in T-lymphocyte migration to the infection site by acting as a chemotactic receptor (PubMed:30713770)
- Specific Function
- actin binding
- Gene Name
- CCR5
- Uniprot ID
- P51681
- Uniprot Name
- C-C chemokine receptor type 5
- Molecular Weight
- 40523.645 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General 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 (PubMed:10452968, PubMed:18799424, PubMed:24912431, PubMed:28978524). Involved in the AKT signaling cascade (PubMed:24912431). Plays a role in regulation of cell migration, e.g. during wound healing (PubMed:28978524). Acts as a receptor for extracellular ubiquitin; leading to enhanced intracellular calcium ions and reduced cellular cAMP levels (PubMed:20228059). Binds bacterial lipopolysaccharide (LPS) et mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Involved in hematopoiesis and in cardiac ventricular septum formation. Also plays an essential role in vascularization of the gastrointestinal tract, probably by regulating vascular branching and/or remodeling processes in endothelial cells. Involved in cerebellar development. In the CNS, could mediate hippocampal-neuron survival (By similarity)
- Specific Function
- actin binding
- Gene Name
- CXCR4
- Uniprot ID
- P61073
- Uniprot Name
- C-X-C chemokine receptor type 4
- Molecular Weight
- 39745.055 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primarily as a coreceptor for MHC class II molecule:peptide complex. The antigens presented by class II peptides are derived from extracellular proteins while class I peptides are derived from cytosolic proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class II presented by antigen presenting cells (APCs). In turn, recruits the Src kinase LCK to the vicinity of the TCR-CD3 complex. LCK then initiates different intracellular signaling pathways by phosphorylating various substrates ultimately leading to lymphokine production, motility, adhesion and activation of T-helper cells. In other cells such as macrophages or NK cells, plays a role in differentiation/activation, cytokine expression and cell migration in a TCR/LCK-independent pathway. Participates in the development of T-helper cells in the thymus and triggers the differentiation of monocytes into functional mature macrophages
- Specific Function
- coreceptor activity
- Gene Name
- CD4
- Uniprot ID
- P01730
- Uniprot Name
- T-cell surface glycoprotein CD4
- Molecular Weight
- 51110.205 Da
Drug created at October 20, 2016 23:40 / Updated at October 11, 2024 22:08