Susoctocog alfa API Manufacturers

General Description:

Susoctocog alfa, identified by CAS number 1339940-90-7, is a notable compound with significant therapeutic applications. Intravenous susoctocog alfa is a recombinant, B-domain deleted, porcine sequence antihaemophilic factor VIII (FVIII) product that has recently been approved for the treatment of bleeding episodes in adults with acquired haemophilia A (AHA). AHA is a rare bleeding disorder that results in a prolonged clotting time as measured by the activated partial thromboplastin time (aPTT) assay, a conventional in vitro test for biological activity of factor VIII. Patients with AHA have normal Factor VIII genes for coagulation pathways but develop inhibitory autoantibodies directed against Factor VIII. These autoantibodies neutralize circulating human factor VIII and create a functional deficiency of this procoagulant protein. Susoctocog alfa serves to temporarily restore the inhibited endogenous Factor VIII for effective hemostasis. In a global, prospective, controlled, multi-center Phase 2/3 open-label clinical trial, all patients responded to susoctocog alfa treatment within 24 hours . Susoctocog alfa is a glycoprotein containing a 90 kDa heavy chain and a 80 kDa light chain with the naturally-occuring B domain replaced with a twenty-four amino acid linker. Susoctocog alfa was approved by the FDA in October 2014 and is marketed under the brand name Obizur for intravenous injection. It is the first recombinant porcine FVIII treatment approved for AHA that allows physicians to manage the treatment's efficacy and safety by measuring factor VIII activity levels in addition to clinical assessments . The recombinant porcine sequence allows less susceptibility to inactivation by circulating human factor VIII antibodies.

Indications:

This drug is primarily indicated for: Indicated for the treatment of bleeding episodes in adults with acquired hemophilia A. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Absorption:

The absorption characteristics of Susoctocog alfa are crucial for its therapeutic efficacy: The time to reach peak plasma concentrations (Tmax) is approximately 26 minutes or 0.42 hour following intravenous administration of 5000U susoctocog alfa in patients with acquired haemophilia in a non-bleeding state . The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Susoctocog alfa is an important consideration for its dosing schedule: The terminal half-life ranges from 2-17 hours in a non-bleeding state. Following intravenous dose of 5000U to patients with acquired haemophilia in a non-bleeding state, the terminal half life was approximately 3.8 hours . This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Susoctocog alfa exhibits a strong affinity for binding with plasma proteins: Circulating susoctocog alfa binds to endogenous von Willebrand factor endogenously present in the circulation . This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Volume of Distribution:

Susoctocog alfa is distributed throughout the body with a volume of distribution of: Following intravenous dose of 5000U to patients with acquired haemophilia in a non-bleeding state, the volume of distribution at steady state was 30.7 U/% . This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Susoctocog alfa is a critical factor in determining its safe and effective dosage: Following intravenous dose of 5000U to patients with acquired haemophilia in a non-bleeding state, the clearance rate was approximately 4.80 U/% * t . It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Susoctocog alfa exerts its therapeutic effects through: Following susoctocog alfa administration, the activated partial thromboplastin time (aPTT) is expected to normalize indicating restored biological activity of factor VIII and normal clotting time . In a prospective, open-label clinical trail involving 28 subjects with acquired haemophilia A, all subjects had a positive response to treatment for the initial bleeding episodes at 24 hours after dosing where bleeding was either stopped or substantially reduced . The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Susoctocog alfa functions by: Factor VIII circulates in the plasma as a hemostatically active protein complex that consists of factor VIII and a large carrier protein von Willebrand factor via a non-covalent binding interaction. This protein complex remains inactive until the coagulation cascade is activated which in turn activates factor VIII to be released from factor VIII/von Willebrand factor complex. Activated factor VIII acts as a cofactor for factor IX-mediated conversion of factor X to activated factor X. Activated factor X is critical in converting prothrombin into thrombin and sequentially, thrombin converts fibrinogen to fibrin for the formation of a blood clot . Acquired haemophilia is a rare bleeding disorder where patients with normal Factor VIII genes spontaneously develop inhibitory autoantibodies directed against Factor VIII. These autoantibodies are IgG1 and IgG4 autoantibodies that bind to the A2, A3 and C2 domains of the FVIII molecules to inactivate them . The autoantibodies neutralize circulating human factor VIII and create a functional deficiency of this procoagulant protein. Susoctocog alfa serves to temporarily restore the inhibited endogenous Factor VIII for effective hemostasis. Circulating inhibitory autoantibodies have minimal or no cross-reactivity against susoctocog alfa . This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Susoctocog alfa 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:

Susoctocog alfa is categorized under the following therapeutic classes: Blood and Blood Forming Organs, Blood Coagulation Factors, Hemostatics. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Susoctocog alfa include:

• Molecular Weight: 170000.0