Damoctocog alfa pegol API Manufacturers

General Description:

Damoctocog alfa pegol, identified by CAS number 1363853-26-2, is a notable compound with significant therapeutic applications. In recent years, various extended half-life factor VIII and factor IX preparations have been studied and gained approval. In order to extend half-lives, techniques such as fusion to protein conjugates (Fc part of IgG1 or albumin), chemical modification (PEGylation), and protein sequence modification have been utilized. Also known as, BAY94-9027, Damoctocog alfa pegol is a longer-acting Factor VIII therapy formulated with polyethylene glycol (PEG) to reduce the number of infusions necessary to prevent bleeds in patients diagnosed with Haemophilia A. This product has been engineered by Bayer and a biological license application has been filed with the FDA in August 2017 and FDA approved in August 2018.

Indications:

This drug is primarily indicated for: Indicated for use in previously treated adults and adolescents (12 years of age and above) with hemophilia A (congenital Factor VIII deficiency) for: On-demand treatment and control of bleeding episodes , perioperative management of bleeding , and routine prophylaxis to reduce the frequency of bleeding episodes . Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Absorption:

The absorption characteristics of Damoctocog alfa pegol are crucial for its therapeutic efficacy: After a single dose, AUC (area under the curve) was 1640 ± 550 with a dose of 25 IU/kg. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Damoctocog alfa pegol is an important consideration for its dosing schedule: 18.6 ± 4.6h after a single dose. This determines the duration of action and helps in formulating effective dosing regimens.

Clearance:

The clearance rate of Damoctocog alfa pegol is a critical factor in determining its safe and effective dosage: 142 ± 33 mL/h on with a dose of 25 IU/kg and 121 ± 53 mL/h with a dose of 60 IU/kg . It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Damoctocog alfa pegol exerts its therapeutic effects through: This agent is engineered to prolong blood FVIII activity while maintaining coagulation activity using PEGylation, where a PEG (Polyethylene glycol) molecule is continually attached to the factor VIII protein at a specific site , . This prevents and controls bleeding episodes associated with hemophilia A. The aPTT is prolonged in people diagnosed with hemophilia A. The determination of aPTT is a conventional in vitro assay for assessing the biological activity of Factor VIII. Treatment with damoctogog alfa pegol normalizes the aPTT similar to that achieved with plasma-derived Factor VIII. The administration of this agent increases plasma levels of Factor VIII and can temporarily correct the coagulation defect that exists in hemophilia A patients . The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Damoctocog alfa pegol functions by: This drug is a site-specifically PEGylated recombinant antihemophilic factor, which temporarily replaces the missing coagulation Factor VIII. The site-specific PEGylation in the A3 domain reduces binding to the physiological Factor VIII clearance receptors resulting in a longer half-life and increased AUC (area under the curve) . The active protein, prior to conjugation is a recombinant B-domain deleted human coagulation Factor VIII (BDD-rFVIII) produced by recombinant DNA technology in Baby Hamster Kidney (BHK) cells . Damoctagol alfa pegol is manufactured by site-specific conjugation of the BDD-rFVIII variant K1804C at the cysteine amino acid position 1804 (within the A3 domain) with a single maleimide-derivatized, 60 kilodalton (kDa) branched PEG (two 30 kDa PEG) moiety. The A3 domain was identified and selected for conjugation to provide both a continual coagulation activity and high PEGylation efficiency . This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Damoctocog alfa pegol 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:

Damoctocog alfa pegol is categorized under the following therapeutic classes: Blood Coagulation Factors, Pegylated agents. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Damoctocog alfa pegol include:

• Molecular Weight: 234.0