Spesolimab API Manufacturers

General Description:

Spesolimab, identified by CAS number 2097104-58-8, is a notable compound with significant therapeutic applications. Spesolimab is an interleukin-36 (IL-36) receptor antagonist. It is a humanized monoclonal immunoglobulin G1 antibody that was produced in Chinese hamster ovary (CHO) cells by recombinant DNA technology. The biosimilar of the drug, spesolimab-sbzo, was first approved by the FDA in September 2022 to treat generalized pustular psoriasis flares. Spesolimab works by inhibiting the inflammatory signaling pathway of IL-36, which is often overexpressed and aberrantly overactive in generalized pustular psoriasis. In October 2022, the EMA's Committee for Medicinal Products for Human Use (CHMP) recommended spesolimab be granted marketing authorization for the treatment of flares in adult patients with generalised pustular psoriasis.

Indications:

This drug is primarily indicated for: Spesolimab is indicated for the treatment of generalized pustular psoriasis (GPP) flares in adults. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Spesolimab undergoes metabolic processing primarily in: The metabolic pathway of spesolimab-sbzo has not been characterized. As a humanized IgG1 monoclonal antibody, spesolimab-sbzo is expected to be degraded into small peptides and amino acids via catabolic pathways in a manner similar to endogenous IgG. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Spesolimab are crucial for its therapeutic efficacy: A population pharmacokinetic model was developed based on data collected from healthy subjects, patients with GPP, and patients with other diseases. After a single intravenous dose of 900 mg of spesolimab, the population PK model-estimated AUC_0-∞ (95% CI) and C_max (95% CI) in a typical anti-drug antibody (ADA)-negative patient with GPP were 4750 (4510, 4970) mcg x day/mL and 238 (218, 256) mcg/mL, respectively. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Spesolimab is an important consideration for its dosing schedule: The terminal half-life is 25.5 (24.4, 26.3) days. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Spesolimab exhibits a strong affinity for binding with plasma proteins: There is no information available. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Spesolimab from the body primarily occurs through: There is no information available. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Spesolimab is distributed throughout the body with a volume of distribution of: Based on the population pharmacokinetic analysis, the typical total volume of distribution at steady state was 6.4 L. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Spesolimab is a critical factor in determining its safe and effective dosage: In the linear dose range (0.3 to 20 mg/kg), based on the population PK model, spesolimab-sbzo clearance (95% CI) in a typical GPP patient without anti-drug antibodies, weighing 70 kg was 0.184 (0.175, 0.194) L/day. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Spesolimab exerts its therapeutic effects through: Spesolimab works to reduce inflammation in GPP in a rapid and sustained manner by blocking inflammatory pathways. In clinical trials, spesolimab reduced pustules and improved other disease measures in patients with GPP, irrespective of _IL36RN_ gene mutation status. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Spesolimab functions by: Pustular psoriasis is a type of psoriasis, a chronic and recurrent immune-mediated multisystem disorder. Based on the characteristics and distribution of pustules, the disorder has different phenotypes, such as GPP. While the pathophysiology of psoriasis is not fully understood, some pro-inflammatory cytokines involved in innate and adaptive immune systems have been implicated as key mediators of psoriatic disease. Interleukin (IL)-36 is one of those cytokines whereby unregulated activation and expression of IL-36 - often due to _IL36RN_ gene mutations - can result in pathological autoinflammatory responses in pustular psoriasis. IL-36 is expressed in epithelial and immune cells and has three members, IL-36α, IL-36β, and IL-36γ, that bind to a receptor complex to activate pro-inflammatory and pro-fibrotic downstream signalling pathways, such as increased expression and actions of pro-inflammatory cells and factors. The heterodimeric receptor complex IL-36R comprises an IL-1RL2 subunit - to which IL-36 binds - and an IL-1RAcP co-receptor. The exact mechanism of action of spesolimab in managing psoriatic flares is unclear; however, it is believed to ameliorate inflammation by inhibiting IL-36 signalling. Spesolimab binds to the IL-36R receptor complex, preventing the binding of IL-36 downstream activation of receptor signalling pathways. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Spesolimab 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:

Spesolimab is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Antibodies, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antineoplastic and Immunomodulating Agents, Blood Proteins, Globulins, Immunoglobulins, Immunoproteins, Immunosuppressive Agents, Interleukin Inhibitors, 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 Spesolimab include:

• Molecular Weight: 146000.0
• Molecular Formula: C6480H9988N1736O2012S46