Mosunetuzumab API Manufacturers

General Description:

Mosunetuzumab, identified by CAS number 1905409-39-3, is a notable compound with significant therapeutic applications. Mosunetuzumab is a humanized anti-CD20/CD3 bispecific antibody. It can recognize and bind two different targets simultaneously, CD20 on cancer B-cells and CD3 on T-cells, allowing it to redirect T-cell cytotoxic activity to cancer cells. The standard of care for patients with B-cell lymphoma includes an anti-CD20 monoclonal antibody, such as , in combination with chemotherapy. However, patients with certain types of B-cell lymphoma, such as follicular lymphoma (FL), chronic lymphocytic leukemia (CLL) or aggressive B-cell lymphoma, have a high probability of relapse or recurrence after treatment. Mosunetuzumab has the potential to circumvent resistance to in patients with follicular lymphoma, and unlike CAR-T therapies such as and , it is an “off-the-shelf” alternative, readily available to patients. In June 2022, the European Medicines Agency approved mosunetuzumab for the treatment of adult patients with relapsed or refractory (R/R) FL who have received at least two prior systemic therapies.

Indications:

This drug is primarily indicated for: Mosunetuzumab as monotherapy is indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic therapies. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Mosunetuzumab undergoes metabolic processing primarily in: Mosunetuzumab is a protein therapeutic; it is expected to be degraded into small peptides and amino acids via catabolic pathways. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Mosunetuzumab are crucial for its therapeutic efficacy: Between 0.05 and 60 mg, mosunetuzumab follows a dose-proportional pharmacokinetic profile. The population pharmacokinetics of intravenous mosunetuzumab are described with a two-compartment pharmacokinetic model with time-dependent clearance. After two cycles of mosunetuzumab (42 days, given by intravenous infusion), patients reached a C_max of 17.9 µg/mL at the end of dose of Cycle 2 Day 1. The average AUC of two cycles of mosunetuzumab was 126 µg⋅day/mL. In patients with relapsed or refractory B-cell non-Hodgkin's lymphoma treated with mosunetuzumab, serum concentration reached the C_max at the end of the intravenous infusion and declined in a bi-exponential fashion. Mosunetuzumab is expected to have a bioavailability close to 100% when given intravenously. In clinical trials, mosunetuzumab administered subcutaneously had a slow absorption rate and high bioavailability (>75%). The pharmacokinetics of mosunetuzumab was similar in Asian and non-Asian subjects. Compared to males, the steady-state clearance of mosunetuzumab in females is marginally lower (approximately 13%), and dose adjustment based on gender is not required. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Mosunetuzumab is an important consideration for its dosing schedule: Mosunetuzumab has a terminal half-life of 16.1 days, and an apparent half-life between 6 and 11 days. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Mosunetuzumab exhibits a strong affinity for binding with plasma proteins: Mosunetuzumab is a bispecific antibody; therefore, protein binding studies were not carried out. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Mosunetuzumab from the body primarily occurs through: Since mosunetuzumab is an immunoglobulin G (IgG) antibody, it is expected to be mainly eliminated via intracellular catabolism. Hepatic or renal impairment is not expected to influence the elimination of mosunetuzumab. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Mosunetuzumab is distributed throughout the body with a volume of distribution of: The estimated central volume of distribution for mosunetuzumab administered via intravenous infusion is 5.49 L. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Mosunetuzumab is a critical factor in determining its safe and effective dosage: The mean steady-state plateau clearance (CL_ss) of mosunetuzumab is 1.08 L/day, and its baseline clearance (CL_base) is 0.584 L/day. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Mosunetuzumab exerts its therapeutic effects through: Mosunetuzumab is an anti-CD20/CD3 bispecific antibody that leads to B-cell depletion (CD19 B-cell counts < 0.07 x 109/L) and hypogammaglobulinemia (IgG levels < 500 mg/dL). In patients with aggressive non-Hodgkin's lymphoma (NHL) treated with mosunetuzumab, the overall response rate (ORR) was 37.4%, and the complete remission (CR) rate was 19.5%, while patients with indolent NHL treated with mosunetuzumab had an ORR of 62.7% and a CR rate of 43.3%. The response to mosunetuzumab in a high-risk group of patients with progression of follicular lymphoma within 24 months after initiating frontline treatment (n=29) was also beneficial; the ORR was 75.9% and the CR rate was 55.2%. Patients treated with mosunetuzumab may develop cytokine release syndrome (CRS), including life-threatening reactions. CRS mainly occurred on days 1 and 15 of cycle 1. To avoid CRS, patients should receive corticosteroids, antipyretics and antihistamines prior to mosunetuzumab therapy. Serious infections such as pneumonia, bacteremia, and sepsis or septic shock have been reported in patients treated with mosunetuzumab, and caution should be exercised in patients with a history of recurring or chronic infections. Tumour flare and tumour lysis syndrome (TLS) have also been reported in patients treated with mosunetuzumab. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Mosunetuzumab functions by: Mosunetuzumab is a full-length, humanized anti-CD20/CD3 bispecific antibody that targets CD20-expressing B-cells. Unlike B-cell-targeting monoclonal antibodies, such as , mosunetuzumab can recognize and bind two different targets, CD20 on cancer B-cells and CD3 on T-cells in a 1:1 ratio. Mosunetuzumab is a conditional agonist; the targeted killing of CD20-expressing B-cells is observed only when this drug is simultaneously bound to CD20 on B-cells and CD3 on T-cells. Mosunetuzumab recruits T-cells and leads to their activation by promoting the formation of an immunologic synapse between a target B-cell and a cytotoxic T-cell. The activation of T-cells leads to the directed release of perforin and granzymes through the immunologic synapsis, which ultimately induces B-cell lysis and cell death. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Mosunetuzumab 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:

Mosunetuzumab is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Blood Proteins, Cancer immunotherapy, CD20-directed Antibody Interactions, CD3-directed Antibody Interactions, Immunoglobulins, Immunosuppressive Agents, Immunotherapy, Myelosuppressive Agents, 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 Mosunetuzumab include:

• Molecular Weight: 146300.0
• Molecular Formula: C6515H10031N1725O2025S43