Susoctocog alfa

Identification

Summary

Susoctocog alfa is a recombinant Factor VIII used to treat and prevent bleeding in hemophilia A.

Brand Names

Obizur

Generic Name

Susoctocog alfa

DrugBank Accession Number

DB11606

Background

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 ². 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 ². The recombinant porcine sequence allows less susceptibility to inactivation by circulating human factor VIII antibodies.

Type

Biotech

Groups

Approved, Investigational

Biologic Classification

Protein Based Therapies
Blood factors

Protein Chemical Formula

Not Available

Protein Average Weight

170000.0 Da (Approximate, B-Domain deleted)

Sequences

Not Available

Synonyms

Antihemophilic factor (recombinant) porcine sequence
ANTIHEMOPHILIC FACTOR (RECOMBINANT), PORCINE SEQUENCE
Antihemophilic factor porcine, B-domain truncated recombinant
Porcine recombinant factor VIII B-domain truncated
RECOMBINANT DNA DERIVED B-DOMAIN DELETED PORCINE BLOODCOAGULATION FACTOR VIII ANALOGUE, PRODUCED IN BHK21 CELLS: DES-(753-1418)-BLOOD-COAGULATION FACTOR VIII (PROCOAGULANT COMPONENT) SUS SCROFA, GLYCOSYLATED
Susoctocog alfa

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Pharmacology

Indication

Indicated for the treatment of bleeding episodes in adults with acquired hemophilia A.

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Management of	Bleeding		••••••••••••

Contraindications & Blackbox Warnings

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Pharmacodynamics

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 ³. 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 ³.

Mechanism of action

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 ^Label.

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 ¹. 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 ^Label.

Target	Actions	Organism
Avon Willebrand factor	binding	Humans

Absorption

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 ^Label.

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/% ³.

Protein binding

Circulating susoctocog alfa binds to endogenous von Willebrand factor endogenously present in the circulation ^Label.

Metabolism

Not Available

Route of elimination

Not Available

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 ³.

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 ³.

Adverse Effects

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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 ³.

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
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Abciximab	The therapeutic efficacy of Susoctocog alfa can be decreased when used in combination with Abciximab.
Acenocoumarol	The therapeutic efficacy of Susoctocog alfa can be decreased when used in combination with Acenocoumarol.
Alpha-1-proteinase inhibitor	Alpha-1-proteinase inhibitor may increase the thrombogenic activities of Susoctocog alfa.
Alteplase	The therapeutic efficacy of Susoctocog alfa can be decreased when used in combination with Alteplase.
Aminocaproic acid	The risk or severity of adverse effects can be increased when Aminocaproic acid is combined with Susoctocog alfa.

Food Interactions

No interactions found.

Products

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Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Obizur	Injection, powder, for solution	500 U	Intravenous	Baxalta Innovations Gmb H	2016-09-08	Not applicable
Obizur	Powder, for solution	500 unit / mL	Intravenous	Takeda	2016-11-30	Not applicable
Obizur	Injection, powder, for solution	500 U	Intravenous	Baxalta Innovations Gmb H	2016-09-08	Not applicable
Obizur	Injection, powder, lyophilized, for solution; Kit	500 [USP'U]/1mL	Intravenous	Takeda Pharmaceuticals America, Inc.	2014-10-23	Not applicable
Obizur	Injection, powder, for solution	500 U	Intravenous	Baxalta Innovations Gmb H	2016-09-08	Not applicable

Chemical Identifiers

UNII: 6892UQT2GK
CAS number: 1339940-90-7

References

General References

Burness CB, Scott LJ: Susoctocog Alfa: A Review in Acquired Haemophilia A. Drugs. 2016 May;76(7):815-21. doi: 10.1007/s40265-016-0576-1. [Article]
FDA Approves Baxter's OBIZUR [Antihemophilic Factor (Recombinant), Porcine Sequence], for Acquired Hemophilia A [Link]
Obizur Product Information [Link]

External Links

PubChem Substance: 347911216
RxNav: 1592899
Wikipedia: Susoctocog_alfa

FDA label

Download (356 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
3	Terminated	Treatment	Hemophilia A	1
2, 3	Completed	Treatment	Hemophilia A, Acquired	1
Not Available	Completed	Not Available	Hemophilia A, Acquired	2

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection, powder, for solution	Intravenous	500 U
Injection, powder, for solution	Intravenous; Parenteral	500 U
Injection, powder, lyophilized, for solution; kit	Intravenous	500 [USP'U]/1mL
Powder, for solution	Intravenous	500 unit / mL

Prices

Not Available

Patents

Not Available

Properties

State: Solid
Experimental Properties: Not Available

Targets

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Details1. von Willebrand factor

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Binding

General Function: Protein n-terminus binding
Specific Function: Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surf...
Gene Name: VWF
Uniprot ID: P04275
Uniprot Name: von Willebrand factor
Molecular Weight: 309261.83 Da

Drug created at June 22, 2016 16:51 / Updated at July 07, 2023 12:10

Susoctocog alfa

Identification

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Targets