Amivantamab API Manufacturers

General Description:

Amivantamab, identified by CAS number 2171511-58-1, is a notable compound with significant therapeutic applications. Amivantamab, also known as JNJ-61186372, is an anti-EGFR-MET bispecific antibody, derived from Chinese hamster ovary cells, approved for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. Patients with NSCLC often develop resistance to drugs that target EGFR and MET individually, so amivantamab was developed to attack both targets, reducing the chance of resistance developing. Amivantamab was found to be more effective than the EGFR inhibitor or the MET inhibitor _in vivo_. Patients with NSCLC with exon 20 insertion mutations in EGFR do not respond to tyrosine kinase inhibitors, and were generally treated with platinum-based therapy. Amivantamab was granted FDA approval on 21 May 2021, followed by the approval by the EMA on 9 December 2021 and Health Canada on 30 March 2022.

Indications:

This drug is primarily indicated for: Amivantamab is indicated in the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, whose disease has progressed on or after platinum-based chemotherapy. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Amivantamab undergoes metabolic processing primarily in: Antibodies are expected to be metabolized to oligopeptides and amino acids. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Half-life:

The half-life of Amivantamab is an important consideration for its dosing schedule: The terminal half life of amivantamab-vmjw is 11.3 ± 4.53 days. This determines the duration of action and helps in formulating effective dosing regimens.

Volume of Distribution:

Amivantamab is distributed throughout the body with a volume of distribution of: The mean volume of distribution of amivantamab-vmjw is 5.13 ±1.78 L. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Amivantamab is a critical factor in determining its safe and effective dosage: The mean clearance of amivantamab-vmjw is 360 ± 144 mL/day. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Amivantamab exerts its therapeutic effects through: Amivantamab is an EGF and MET receptor targeted antibody indicated in the treatment of non-small cell lung cancer with an EGFR 20 exon insertion mutation. It has a long duration of action, as activity can be detected up to 8 weeks after treatment. Patients should be counselled regarding the risk of infusion-related reactions, interstitial lung disease and pneumonitis, skin reactions, ocular toxicity, and paronychia. Patients should not take amivantamab if they are pregnant or breastfeeding. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Amivantamab functions by: Mesenchymal-epithelial transition factor (MET) is a receptor with tyrosine kinase activity expressed on epithelial cells that, upon signalling, dimerizes and activates downstream pathways that signal cell division. The Epidermal Growth Factor Receptor (EGFR) is a transmembrane protein with tyrosine kinase activity that can further activate downstream pathways that signal cell division, survival, and angiogenesis. Patients with NSCLC with exon 20 insertion mutations in EGFR do not respond to tyrosine kinase inhibitors, and are generally treated with platinum-based therapy. Exon 20 insertion mutations in EGFR also lead to conformational changes that activate EGFR. Amivantamab targets both EGFR and MET, preventing ligands from binding to the receptors, blocking signalling, marking the cancerous cells for antibody-dependant cellular cytotoxicity by natural killer cells, and allowing macrophages to perform trogocytosis. Amivantamab's binding to the EGFR H epitope shares some of the same amino acids that binds to. Amivantamab's binding to the alpha chain of MET stabilizes the Sema domain loop 1 to 2 in a position 6 Angstroms away from the position it would be in under normal binding, preventing its interaction with the hepatocyte growth factor's (HGF) beta chain. Another smaller conformational change in the MET Sema domain loop 1 to 3 also contributes to preventing the interaction of the MET Sema domain with HGF's beta chain. HGF is no longer able to bind to MET, preventing downstream signalling. Amivantamab's Fc portion contains 90% less fucose than normal antibodies, allowing for increased binding to the FcγRIIIa region. Binding of the Fc portion of Amivantamab signals the complement system and innate immune system to target the bound cells for complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and antibody-dependent cellular phagocytosis. Binding of amivantamab to the Fc receptor also leads to and increase in levels of IFNγ. Amivantamab also significantly downregulates the expression of EGFR and MET on NSCLC cell surfaces, further reducing downstream signalling. EGFR and MET on the cell surface are internalized, and possibly degrading by fusing endosomes with lysosomes. Alternatively, EGFR and MET are the subjects of monocyte-dependent trogocytosis. Trogocytosis allows monocytes to internalize and break down EGFR and MET from the NSCLC cells without cytotoxicity, downmodulating EGFR and MET receptors. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Amivantamab 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:

Amivantamab is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Antibodies, Antibodies, Monoclonal, Antineoplastic Agents, Antineoplastic Agents, Immunological, Antineoplastic and Immunomodulating Agents, Bispecific Monoclonal Antibodies, Blood Proteins, Globulins, Immunoglobulins, Immunoproteins, MONOCLONAL ANTIBODIES AND ANTIBODY DRUG CONJUGATES, Proteins, Serum Globulins. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Amivantamab include:

• Molecular Weight: 148000.0