Susoctocog alfa

Identification

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Name
Susoctocog alfa
Accession Number
DB11606
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Blood factors
Description

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.

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 porcine, B-domain truncated recombinant
  • Porcine recombinant factor VIII B-domain truncated
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ObizurPowder, for solution500 unitIntravenousBaxalta Canada Corporation2016-11-30Not applicableCanada
ObizurInjection, powder, for solution500 UIntravenousBaxalta Innovations Gmb H2015-11-11Not applicableEu
ObizurInjection, powder, for solution500 UIntravenousBaxalta Innovations Gmb H2015-11-11Not applicableEu
ObizurInjection, powder, for solution500 UIntravenousBaxalta Innovations Gmb H2015-11-11Not applicableEu
ObizurKit500 [USP'U]/1mLBaxalta US Inc.2014-10-23Not applicableUs
Additional Data Available
  • Application Number
    Application Number

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  • Product Code
    Product Code

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Categories
UNII
6892UQT2GK
CAS number
1339940-90-7

Pharmacology

Indication

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

Associated Conditions
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.

TargetActionsOrganism
Avon Willebrand factor
binding
Humans
Additional Data Available
Adverse Effects

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Additional Data Available
Contraindications

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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.

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.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe therapeutic efficacy of Susoctocog alfa can be decreased when used in combination with (R)-warfarin.
(S)-WarfarinThe therapeutic efficacy of Susoctocog alfa can be decreased when used in combination with (S)-Warfarin.
4-hydroxycoumarinThe therapeutic efficacy of Susoctocog alfa can be decreased when used in combination with 4-hydroxycoumarin.
AbciximabThe therapeutic efficacy of Susoctocog alfa can be decreased when used in combination with Abciximab.
AcenocoumarolThe therapeutic efficacy of Susoctocog alfa can be decreased when used in combination with Acenocoumarol.
Acetylsalicylic acidThe therapeutic efficacy of Susoctocog alfa can be decreased when used in combination with Acetylsalicylic acid.
Alpha-1-proteinase inhibitorAlpha-1-proteinase inhibitor may increase the thrombogenic activities of Susoctocog alfa.
AlteplaseThe therapeutic efficacy of Susoctocog alfa can be decreased when used in combination with Alteplase.
AmediplaseThe therapeutic efficacy of Susoctocog alfa can be decreased when used in combination with Amediplase.
Aminocaproic AcidThe risk or severity of adverse effects can be increased when Aminocaproic Acid is combined with Susoctocog alfa.
Additional Data Available
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Food Interactions
Not Available

References

General References
  1. 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. [PubMed:27098420]
  2. FDA Approves Baxter's OBIZUR [Antihemophilic Factor (Recombinant), Porcine Sequence], for Acquired Hemophilia A [Link]
  3. Obizur Product Information [Link]
External Links
PubChem Substance
347911216
ATC Codes
B02BD14 — Susoctocog alfa
AHFS Codes
  • 20:28.16 — Hemostatics
FDA label
Download (356 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3RecruitingTreatmentHemophilia A1
Not AvailableActive Not RecruitingNot AvailableAcquired Hemophilia A1
Not AvailableRecruitingNot AvailableAcquired Hemophilia A1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, powder, for solutionIntravenous500 U
Kit500 [USP'U]/1mL
Powder, for solutionIntravenous500 unit
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

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 on June 22, 2016 10:51 / Updated on July 21, 2019 06:38