Inotuzumab ozogamicin API Manufacturers

General Description:

Inotuzumab ozogamicin, identified by CAS number 635715-01-4, is a notable compound with significant therapeutic applications. Inotuzumab ozogamicin is an antibody-drug conjugate using linker and cytotoxic drug technology similar to that developed for the ground-breaking treatment Mylotarg (), which was approved by the US FDA in 2000 for the treatment of acute myeloid leukaemia. Inotuzumab ozogamicin consists of a recombinant humanised IgG4 kappa CD22-targeting monoclonal antibody covalently attached to calicheamicin derivative, N-acetyl-gamma-calicheamicin dimethylhydrazide, which is a potent DNA-binding cytotoxic agent . Developed by Pfizer and UCB, inotuzumab ozogamicin was granted approval by EU in June 2017 followed by FDA on August 17th, 2017 for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). ALL is a rapidly progressing cancer of the bone marrow that is associated with high mortality rates and low therapeutic response from standard chemotherapies in relasping conditions. In a randomized trial, inotuzumab ozogamicin displayed higher percentages of patients undergoing longer periods of complete remission with no evidence of disease in comparison to patients receiving alternative chemotherapy .

Indications:

This drug is primarily indicated for: Indicated as monotherapy for the treatment of adults with relapsed or refractory CD22-positive B cell precursor acute lymphoblastic leukaemia (ALL). Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Inotuzumab ozogamicin undergoes metabolic processing primarily in: N-acetyl-gamma-calicheamicin dimethylhydrazide primarily undergoes nonenzymatic reduction *in vitro*. The metabolism of N-acetyl-gamma-calicheamicin dimethylhydrazide in human serum is not clearly understood as the level of the drug is below the limit of quantification of 50 pg/mL . The antibody portion of the drug is thought to undergo proteolytic degradation into amino acids then recycled into other proteins . This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Inotuzumab ozogamicin are crucial for its therapeutic efficacy: Inotuzumab ozogamicin is intended to be administered in cycles that each run for 3 to 4 weeks. The steady state exposure of the drug is reached by Cycle 4. The mean (SD) maximum serum concentration (Cmax) of inotuzumab ozogamicin was 308 ng/mL (362) with patients receving the recommended dose of 1.8 mg/m^2/cycle . The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Inotuzumab ozogamicin is an important consideration for its dosing schedule: The elimination half life at the end of Cycle 4 of administration is approximately 12.3 days in a 2-compartment model . This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Inotuzumab ozogamicin exhibits a strong affinity for binding with plasma proteins: *In vitro* studies show the binding of the N-acetyl-gamma-calicheamicin dimethylhydrazide to human plasma proteins to be approximately 97% . This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Inotuzumab ozogamicin from the body primarily occurs through: The drug is disposited in the body after administration. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Inotuzumab ozogamicin is distributed throughout the body with a volume of distribution of: The total volume of distribution of inotuzumab ozogamicin is approximately 12L . This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Inotuzumab ozogamicin is a critical factor in determining its safe and effective dosage: The clearance of inotuzumab ozogamicin at steady state is 0.0333 L/h . It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Inotuzumab ozogamicin exerts its therapeutic effects through: Inotuzumab ozogamicin is an antineoplastic agent that targets CD22 antigen expressed on immature B-cell lymphocytes and blocks further growth of tumor cells. The drug aims to restore normal blood counts and achieve complete remission from the disease. QT interval prolongation was observed in patients receiving inotuzumab ozogamicin. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Inotuzumab ozogamicin functions by: Inotuzumab ozogamicin is comprised of cytotoxic antibiotic N-acetyl-gamma-calicheamicin dimethylhydrazide attached to a humanized monoclonal IgG4 antibody via 4-(4 acetylphenoxy) butanoic acid (acetyl butyrate) linker. The drug exerts a potent cytotoxic effect against CD22+ B-cell lymphoma when the antibody binds to the CD22 receptor on the surface of B cells . The drug-CD22 complex is rapidly internalized into the cell, forming an endosome which subsequently fuses with lysosomes. N-acetyl-gamma-calicheamicin dimethylhydrazide is then intracellularly released into the acidic environment. N-acetyl-gamma-calicheamicin dimethylhydrazide is a calicheamicin derivative, which is naturally produced by the bacterium Micromonospora echinospora, and is toxic to the body when not bound to the antibody. It mediates apoptosis of the cell by binding to the minor groove of DNA in a sequence-specific manner and undergoing a structural change to generate diradicals . These changes abstract hydrogen ions from the phosphodiester bonds of double-stranded DNA, resulting in breaks and cell apoptosis . This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Inotuzumab ozogamicin 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:

Inotuzumab ozogamicin is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Antibiotics, Antineoplastic, Antibodies, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antibody-drug Conjugates, Antineoplastic Agents, Antineoplastic Agents, Immunological, Antineoplastic and Immunomodulating Agents, Blood Proteins, Calicheamicins, Cancer immunotherapy, Carbohydrates, CD22 (Clusters of Differentiation 22) inhibitors, CD22-directed Antibody Interactions, CD22-directed Immunoconjugate, Decreased DNA Integrity, Globulins, Glycosides, Hepatotoxic Agents, Immunoconjugates, Immunoglobulins, Immunologic Factors, Immunoproteins, Immunotherapy, Immunotoxins, Increased Cellular Death, MONOCLONAL ANTIBODIES AND ANTIBODY DRUG CONJUGATES, Narrow Therapeutic Index Drugs, Noxae, P-glycoprotein substrates, P-glycoprotein substrates with a Narrow Therapeutic Index, Proteins, Serum Globulins, Toxic Actions. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.