Caplacizumab API Manufacturers

General Description:

Caplacizumab, identified by CAS number 915810-67-2, is a notable compound with significant therapeutic applications. Caplacizumab, firstly called ALX-0081, is a humanized single-variable-domain immunoglobulin consisting of two identical humanized building blocks genetically linked by a three-alanine linker. Caplacizumab was developed by Ablynx, a Sanofi company and FDA approved on February 6, 2019, and approved previously by the EU in October 2018 as a combination therapy with plasma exchange and immunosuppression.

Indications:

This drug is primarily indicated for: Capacizumab is approved for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP) in conjunction with plasma exchange and immunosuppression in patients 18 years or older. aTTP is a rare autoimmune condition presented by a disruption of blood clotting order which is translated into systemic microvascular thrombosis leading to profound thrombocytopenia, hemolytic anemia and organ ischemia. It is caused by the production of autoantibodies against ADAMTS-13 which is the protein in charge of cleaving the von-Wilebrand factor. The lack of this process produces the generation of ultra large von Wilebrand multimers that bind to platelets and form microthrombi and causing thromboembolic complications. Previously, capacizumab was under review for the prevention of thrombosis in high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention but this indication was withdrawn. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Caplacizumab undergoes metabolic processing primarily in: Caplacizumab is degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Caplacizumab are crucial for its therapeutic efficacy: After intravenous administration of caplacizumab, the pharmacokinetic profile is non-linear and to follow a non-compartmental model as the pharmacokinetic profile of this drug is dependent on the expression of von Willebrand factor. After administration, caplacizumab is rapidly absorbed with a dose-dependent behavior. The peak concentration was reached after 6-7 hours and it presents a very high bioavailability reaching approximately 90%. The subcutaneous administration of a dose of 10 mg of caplacizumab produced a peak concentration of 528 ng/ml and an AUC of 7951 ng.h/ml. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Caplacizumab is an important consideration for its dosing schedule: The reported half-life is reported to be in the range of 16-27 hours. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Caplacizumab exhibits a strong affinity for binding with plasma proteins: This antibody acts directly on plasma proteins and thus, this parameter is not significant for drug description. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Caplacizumab from the body primarily occurs through: The elimination of caplacizumab is divided between target-driven disposition which is driven by the binding to the von Willebrand factor and non-target disposition driven by the combination of catabolism and renal elimination. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Caplacizumab is distributed throughout the body with a volume of distribution of: The reported volume of distribution of caplacizumab is 6.33 L. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Caplacizumab is a critical factor in determining its safe and effective dosage: As the elimination is highly divided among hepatic, target-driven and renal elimination, the calculation of the clearance rate is not significant for drug description. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Caplacizumab exerts its therapeutic effects through: _In vitro_ studies have shown a caplacizumab-driven complete inhibition of platelet aggregation and in phase II clinical trials, it was shown to reduce the activity of the von Willebrand factor by 20% from treatment day 1 until treatment day 30. The level of von Willebrand factor in the plasma was also significantly reduced due to the clearance of the von Willebrand-caplacizumab complex. In phase III clinical trials, more than 50% of the tested individuals reached a platelet normal count. In these trials, it was observed as well a significant reduction in the incidence of aTTP as well as a significant reduction in the median time to response of about 39%. However, as caplacizumab does not target autoimmune response, relapses were observed after treatment discontinuation. The last clinical trial prior approval showed production of a platelet count of more than 150,000 per mcl after the cessation of plasma exchange therapy for 5 days as well as a reduction of patient recurrent thrombotic thrombocytopenic purpura and of disease-related death during treatment. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Caplacizumab functions by: Caplacizumab acts by targetting the A1 domain of the ultra-large von Willebrand factor which in order inhibits the interaction with the glycoprotein Ib-IX-V receptor in the platelets. Caplacizumab binds to von Willebrand factor with an affinity of 8.5 nM, thus it is very target specific. The blockage of the von Willebrand factor prevents the interaction between the von Willebrand factor and the platelets, hence, preventing platelet aggregation. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Caplacizumab 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:

Caplacizumab is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Antibodies, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antiplatelet agents, Antithrombotic Agents, Misc, Blood and Blood Forming Organs, Blood Proteins, Globulins, Immunoglobulin Fab Fragments, Immunoglobulin Fragments, Immunoglobulin Variable Region, Immunoglobulins, Immunoproteins, Peptide Fragments, Peptides, Proteins, Serum Globulins, von Willebrand Factor (vWF)-directed Antibodies, von Willebrand Factor, antagonists & inhibitors. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Caplacizumab include:

• Water Solubility: Soluble
• Melting Point: 61 ºC (Fab fragment)
• Boiling Point: Fab fragment denaturates at 60 ºC
• Isoelectric Point: 6.6 - 7.2
• Molecular Weight: 27880.0
• Molecular Formula: C1213H1891N357O380S10