Inebilizumab API Manufacturers

General Description:

Inebilizumab, identified by CAS number 1299440-37-1, is a notable compound with significant therapeutic applications. Inappropriate growth of or self-directed antibody production by B-cells is the etiological underpinning of a variety of conditions, including the multiple sclerosis-like neurological condition neuromyelitis optica spectrum disorder (NMOSD). Inebilizumab is a humanized afucosylated monoclonal IgG1 antibody directed against the broadly expressed B-cell surface antigen CD19. Inebilizumab is cytolytic, resulting in B-cell depletion and offering therapeutic benefit to patients suffering from NMOSD. Compared to the anti-CD20 antibody , which is also used to treat NMOSD, inebilizumab has broader specificity. Inebilizumab was granted FDA approval on June 11, 2020, for the treatment of anti-aquaporin 4 positive NMOSD patients. Given its mechanism of action and good safety profile, it may prove useful in the treatment of other conditions linked to autoimmune antibody production or B-cell malignancies.

Indications:

This drug is primarily indicated for: Inebilizumab is indicated for the treatment of aquaporin-4 (AQP4) immunoglobulin-positive (AQP4-IgG) neuromyelitis optica spectrum disorder (NMOSD) in adult patients. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Inebilizumab undergoes metabolic processing primarily in: Inebilizumab is a monoclonal antibody and is hence likely degraded through proteolysis. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Inebilizumab are crucial for its therapeutic efficacy: Inebilizumab is given intravenously and hence is immediately exposed to the systemic circulation. The mean reported C_max following second dose 300 mg administration was 108 μg/mL, and the cumulative AUC following 26 weeks of treatment with two IV administrations was 2980 μg\*d/mL. In a clinical trial investigating the use of inebilizumab in relapsing multiple sclerosis, the mean C_max corresponding to 30, 100, and 600 mg of inebilizumab was 17.9, 43.1, and 248.0 μg/mL and the AUC_0-∞ was 440, 1150, and 6950 μg\*d/mL. In another trial for patients with systemic sclerosis, the mean C_max varied between 2.7 and 227.0 μg/mL and the AUC_0-∞ varied between 16.1 and 2890.0 μg\*d/mL for doses between 0.1 and 10.0 mg/kg. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Inebilizumab is an important consideration for its dosing schedule: Inebilizumab exhibits biphasic pharmacokinetics with a mean terminal half-life of 18 days. The terminal half-life reported in phase I studies varied by dose but was typically close to 18 days, with a range of 6.8 to 18.7 days. This determines the duration of action and helps in formulating effective dosing regimens.

Volume of Distribution:

Inebilizumab is distributed throughout the body with a volume of distribution of: Inebilizumab has an estimated central volume of distribution of 2.95L and a peripheral volume of distribution of 2.57L. The steady-state volume of distribution in patients administered with a range of doses between 0.1 and 10.0 mg/kg ranged from 53.7 to 71.7 mL/kg. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Inebilizumab is a critical factor in determining its safe and effective dosage: Inebilizumab has an estimated systemic clearance of 0.19 L/day. In phase I studies, the reported clearance varied between 139-180 mL/day in one study, and 3.5-6.2 mL/kg/day in another, depending on the dose. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Inebilizumab exerts its therapeutic effects through: Inebilizumab is a CD19-directed monoclonal antibody that results in immunosuppression through B-cell depletion with sufficient efficacy to allow a six-month dosing schedule. Due to this mechanism of action, patients undergoing inebilizumab treatment may be at higher risk of infections and should be monitored for active infections and immunoglobulin levels while undergoing treatment; vaccination is not recommended during inebilizumab treatment. Also, there is a risk of severe infusion reactions. Animal data suggests the possibility of fetal harm with inebilizumab and therefore, effective contraception during and for six months following inebilizumab treatment is recommended. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Inebilizumab functions by: Neuromyelitis optica spectrum disorder (NMOSD), formerly referred to as Devic's disease, is an antibody-mediated autoimmune condition resulting in astroglial cell death, demyelination, and central nervous system (CNS) inflammation. The presence of anti-aquaporin 4 immunoglobulin (AQP4-IgG) is the most frequent biomarker, although AQP4-IgG negative, anti-myelin oligodendrocyte glycoprotein (anti-MOG) positive, variants with similar presentation also exist. The theoretical origin of symptoms is through AQP4-IgG-mediated astrocyte cytotoxicity and subsequent infiltration of neutrophils, eosinophils, and macrophages, leading to inflammatory-mediated oligodendrocyte damage and myelin sheath loss. In general, this manifests as optic neuritis and transverse myelitis with occasional involvement of the diencephalic, brainstem, and cerebral hemisphere. CD19 is a B-cell surface antigen expressed on most B-cells, including the expanded population of CD27^high CD38^high CD180^- CD19⁺ plasmablasts that are the origin of astrocytic AQP4-IgG in most NMOSD patients. Inebilizumab binds to CD19 and, through one of several potential mechanisms, results in cell death. Destruction of the specific AQP4-IgG-producing plasmablasts results in lower amounts of AQP4-IgG in the CNS and therefore slows neuronal damage and improves patient outcomes. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Inebilizumab 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:

Inebilizumab is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Antibodies, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antineoplastic and Immunomodulating Agents, Blood Proteins, CD19 Directed Cytolytic Antibodies, Globulins, Immunoglobulins, Immunoproteins, Immunosuppressive Agents, Proteins, Selective Immunosuppressants, 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 Inebilizumab include:

• Molecular Weight: 149000.0