Tafasitamab API Manufacturers

General Description:

Tafasitamab, identified by CAS number 1422527-84-1, is a notable compound with significant therapeutic applications. Tafasitamab is a humanized, CD19-directed cytolytic monoclonal antibody intended for the treatment of B-cell malignancies. It is produced using recombinant DNA technology in Chinese hamster ovary cells, and contains an IgG1/2 hybrid Fc-domain which has been modified with 2 amino acid substitutions to enhance its cytotoxicity relative to non-engineered anti-CD19 antibodies. The CD19 surface protein is highly expressed on the surface of B-cells, where it appears to play a role in enhancing B-cell receptor signaling. Its relative ubiquity across different stages of B-cell development, including pre-B and mature B-lymphocytes, as well as its presence in several B-cell malignancies (e.g. chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), diffuse large B-cell lymphoma (DLBCL)) has made it a desirable target in the treatment these B-cell malignancies. Tafasatimab is designed to bind to and block the activity of the CD19 surface antigen, which ultimately results in the lysis of B-cells (both healthy and malignant). Having previously received Breakthrough Therapy, Fast Track, and Orphan designations from the FDA, tafasatimab-cxix (Monjuvi®) received an accelerated approval on July 31st, 2020, for the treatment of relapsed or refractory DLBCL in adult patients who cannot receive autologous stem cell transplants. It must be used in combination with , as this combination results in greater efficacy as compared to either agent alone.

Indications:

This drug is primarily indicated for: Tafasitamab is indicated, in combination with , for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified whom are ineligible for autologous stem cell transplant (ASCT). Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Tafasitamab undergoes metabolic processing primarily in: The biotransformation of tafasitamab has not been elucidated. Most monoclonal antibodies undergo intracellular catabolism via lysosomal degradation to smaller amino acids and peptides. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Tafasitamab are crucial for its therapeutic efficacy: Following intravenous administration of tafasitamab 12 mg/kg on Days 1, 8, 15, and 22 in cycle(s) 1-3 (with an additional dose on Day 4 of cycle 1), mean trough concentrations were 179 (± 53) μg/mL. From cycle 4 onwards, which involve the administration of tafasitamab 12 mg/kg on Days 1 and 15, mean trough concentrations were 153 (± 68) μg/mL. The overall maximum tafasitamab serum concentrations reached were 483 (± 109) μg/mL. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Tafasitamab is an important consideration for its dosing schedule: The terminal elimination half-life of tafasitamab is approximately 17 days. This determines the duration of action and helps in formulating effective dosing regimens.

Route of Elimination:

The elimination of Tafasitamab from the body primarily occurs through: Monoclonal antibodies are typically eliminated via uptake into cells and subsequent catabolism via lysosomal degradation. Due to their large size, they are only eliminated renally under pathologic conditions. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Tafasitamab is distributed throughout the body with a volume of distribution of: The total volume of distribution of tafasitamab following intravenous injection is approximately 9.3 L. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Tafasitamab is a critical factor in determining its safe and effective dosage: The clearance of tafasitamab is approximately 0.41 L/day. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Tafasitamab exerts its therapeutic effects through: Tafasitamab induces a reduction in circulating B-cell counts by binding to a surface antigen, CD19, which is important for their survival. Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) experienced a 97% reduction in peripheral blood B-cell counts following 8 days of treatment, with a 100% reduction reached within 16 weeks of treatment. Tafasitamab can cause infusion-related reactions, particularly during the initial cycles of therapy. Symptoms may include chills, flushing, dyspnea, and hypertension. Patients may be administered premedications (such as , antihistamines, or glucocorticoids) 0.5 - 2 hours prior to infusion to minimize infusion-related reactions. Tafasitamab may also cause significant myelosuppression, and subsequent infection, due to its mechanism of action - patients should undergo monitoring throughout therapy for signs of myelosuppression and/or infection. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Tafasitamab functions by: The CD19 surface antigen is a protein expressed on the surface of pre-B and mature B-lymphocytes that appears to play a role in enhancing B-cell receptor signaling and is considered integral to their survival. These surface proteins are also highly expressed on several B-cell malignancies, such as chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and diffuse large B-cell lymphoma (DLBCL). Tafasitamab is a CD19-directed cytolytic monoclonal antibody that, upon binding and blocking the activity of CD19, causes lysis of B-cells. This process is mediated through both direct apoptosis and immune-mediated effector mechanisms, such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Tafasitamab 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:

Tafasitamab is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Antibodies, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Antineoplastic and Immunomodulating Agents, Blood Proteins, Cancer immunotherapy, Globulins, Immunoglobulins, Immunoproteins, Immunotherapy, Lymphoma, B-Cell, 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 Tafasitamab include:

• Molecular Weight: 150000.0