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General Description:

Ibalizumab, identified by CAS number 680188-33-4, is a notable compound with significant therapeutic applications. 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 . This drug was approved in March 2018 for the management of treatment-resistant HIV . In October 2022, the FDA approved the administration of Trogarzo (ibalizumab-uiyk) by intravenous push, allowing for a faster drug administration.

Indications:

This drug is primarily indicated for: 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 . 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 . Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Ibalizumab undergoes metabolic processing primarily in: Metabolized by CD4 receptor internalization, ibalizumab has no significant impact on liver or kidney metabolism . This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Half-life:

The half-life of Ibalizumab is an important consideration for its dosing schedule: 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 . 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) . This determines the duration of action and helps in formulating effective dosing regimens.

Volume of Distribution:

Ibalizumab is distributed throughout the body with a volume of distribution of: 4.8 L. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Ibalizumab is a critical factor in determining its safe and effective dosage: 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 . It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Ibalizumab exerts its therapeutic effects through: 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 . Trogarzo inhibits viral entry into cells, effectively managing HIV-1 infection in those who have attempted other therapies to no avail . The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Ibalizumab functions by: 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 . Ibalizumab’s post-binding conformational effects block the gp120-CD4 complex from interacting with CCR5 or CXCR4 and thus prevents viral entry and fusion . 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 . 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 . This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Ibalizumab belongs to the None, classified under the direct parent group Peptides. This compound is a part of the Organic Compounds, falling under the Organic Acids superclass, and categorized within the Carboxylic Acids and Derivatives class, specifically within the Amino Acids, Peptides, and Analogues subclass.

Categories:

Ibalizumab is categorized under the following therapeutic classes: 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. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.