Obizur
Obizur Uses, Dosage, Side Effects, Food Interaction and all others data.
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. Obizur 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 . Obizur 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.
Obizur 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.
| Trade Name | Obizur |
| Generic | Susoctocog alfa |
| Susoctocog alfa Other Names | Antihemophilic factor (recombinant) porcine sequence, Antihemophilic factor porcine, B-domain truncated recombinant, Porcine recombinant factor VIII B-domain truncated, Susoctocog alfa |
| Type | Injection, Intravenous |
| Weight | 170000.0 Da (Approximate, B-Domain deleted) |
| Protein binding | Circulating susoctocog alfa binds to endogenous von Willebrand factor endogenously present in the circulation . |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | Shire Pharmaceuticals Limited |
| Available Country | Australia, United Kingdom, United States, |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Obizur is a recombinant Factor VIII used to treat and prevent bleeding in hemophilia A.
Indicated for the treatment of bleeding episodes in adults with acquired hemophilia A.
Obizur is also used to associated treatment for these conditions: Bleeding
How Obizur works
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. Obizur serves to temporarily restore the inhibited endogenous Factor VIII for effective hemostasis. Circulating inhibitory autoantibodies have minimal or no cross-reactivity against susoctocog alfa .
Toxicity
Long-term studies in animals to evaluate the carcinogenic potential, genotoxicity and effects on fertility have not been performed with susoctocog alfa. In repeated-dose studies, the incidence and severity of glomerulopathy observed in monkeys intravenously administered susoctocog alfa at doses of 75, 225 and 750 U/kg/day tended to increase over time .
Food Interaction
No interactions found.Volume of Distribution
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/% .
Elimination Route
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 .
Half Life
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 .
Clearance
Following intravenous dose of 5000U to patients with acquired haemophilia in a non-bleeding state, the clearance rate was approximately 4.80 U/% * t .
Innovators Monograph
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