Simoctocog alfa

Identification

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Name
Simoctocog alfa
Accession Number
DB09108
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Blood factors
Description

Simoctocog alfa is a recombinant B-domain deleted (BDD) rFVIII produced in genetically modified human embryonic kidney (HEK) 293F cells. The harvested product is concentrated and purified by a series of chromatography steps. It is an antihemorrhagic agent used as a replacement therapy in individuals with Haemophilia A who lack the factor VIII in the intrinsic pathway of blood coagulation system. As patients with haemophilia A are predisposed to episodes of recurrent bleeding 2, simoctocog alfa can be administered for the treatment or prevention of bleeding such as prior to surgical procedures.

Simoctocog alfa is a glycoprotein consisting of 1440 amino acids with an approximate molecular mass of 170 kDa, comprising the FVIII domains A1-A2 + A3-C1-C2 whereas the B-domain, present in the full-length plasma-derived FVIII, has been deleted and replaced by a 16 amino acid linker. Simoctocog alfa is a fourth-generation BDD FVIII product made in the human embryonic kidney (HEK) cell line. Full human post-translational modifications via elimination of potentially immunogenic glycosylation patterns found in non-human cell lines led to decreased immunogenicity and longer half-life 1.

Simoctocog alfa is marketed in Europe under the trade name Nuwiq for intravenous injection.

Protein chemical formula
Not Available
Protein average weight
170000.0 Da (Approximate, B-Domain deleted)
Sequences
Not Available
Synonyms
Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NuwiqKit250 [iU]/2.5mLIntravenousOctapharma2016-01-01Not applicableUs
NuwiqKit3000 [iU]/2.5mLIntravenousOctapharma2017-08-01Not applicableUs
NuwiqKit500 [iU]/2.5mLIntravenousOctapharma2016-01-01Not applicableUs
NuwiqKit4000 [iU]/2.5mLIntravenousOctapharma2017-08-01Not applicableUs
NuwiqKit1000 [iU]/2.5mLIntravenousOctapharma2016-01-01Not applicableUs
NuwiqKit2000 [iU]/2.5mLIntravenousOctapharma2016-01-01Not applicableUs
NuwiqKit2500 [iU]/2.5mLIntravenousOctapharma2017-08-01Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
NuwiqSimoctocog alfa (1000 unit) + Water (2.5 ml)Kit; Powder, for solutionIntravenousOctapharma Pharmazeutika Produktionsges M B H2015-12-22Not applicableCanada
NuwiqSimoctocog alfa (2000 unit) + Water (2.5 ml)Kit; Powder, for solutionIntravenousOctapharma Pharmazeutika Produktionsges M B H2015-12-22Not applicableCanada
NuwiqSimoctocog alfa (250 unit) + Water (2.5 ml)Kit; Powder, for solutionIntravenousOctapharma Pharmazeutika Produktionsges M B H2015-12-22Not applicableCanada
NuwiqSimoctocog alfa (500 unit) + Water (2.5 ml)Kit; Powder, for solutionIntravenousOctapharma Pharmazeutika Produktionsges M B H2015-12-22Not applicableCanada
NuwiqSimoctocog alfa (4000 unit) + Water (2.5 ml)Kit; Powder, for solutionIntravenousOctapharma Pharmazeutika Produktionsges M B HNot applicableNot applicableCanada
NuwiqSimoctocog alfa (3000 unit) + Water (2.5 ml)Kit; Powder, for solutionIntravenousOctapharma Pharmazeutika Produktionsges M B HNot applicableNot applicableCanada
NuwiqSimoctocog alfa (2500 unit) + Water (2.5 ml)Kit; Powder, for solutionIntravenousOctapharma Pharmazeutika Produktionsges M B HNot applicableNot applicableCanada
Categories
Not Available
UNII
U50VWW6XH6
CAS number
1219013-68-9

Pharmacology

Indication

Indicated for the treatment and prophylaxis of bleeding in patients of all ages with haemophilia A (congenital factor VIII deficiency) Label.

Associated Conditions
Pharmacodynamics

Simoctocog alfa is an antihemorrhagic agent that displays comparable hemostatic efficacy as the endogenous coagulation factor VIII. Following administration of simoctocog alfa, an increase plasma levels of factor VIII is observed to temporarily correct factor VIII deficiency and bleeding tendencies 2.

Mechanism of action

Haemophilia A is a sex-linked hereditary disorder of blood coagulation due to decreased levels of factor VIII:C. The disorder is associated with episodes of recurrent bleeding and profuse bleeding into joints, muscles or internal organs, either spontaneously or as results of accidental or surgical trauma Label.

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 2,Label.

Simoctocog alfa is an antihemophilic factor that circulates as part of a protein complex with coagulant activity. As a replacement therapy, simoctocog alfa serves to restore the normal levels of factor VIII and allow effective blood clot formation in patients with haemophilia A.

TargetActionsOrganism
Avon Willebrand factor
binding
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

Learn more
Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

Learn more
Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

Learn more
Absorption

At initial assessment following administration of 50 IU/kg simoctocog alfa in adolescent or adult patients with severe haemophilia A, the mean ± SD AUC (FVIII:C) was 17.95 ± 5.57 h·IU/mL/(IU/kg) 2. The mean ± SD maximum plasma concentration divided by the dose (Cmaxnorm) was 0.022 ± 0.003 IU/mL/(IU/kg) 2. The values of mean ± SD AUC (FVIII:C) and Cmaxnorm in pediatric patients were 10.92 ± 3.80 h·IU/mL/(IU/kg) and 0.017 ± 0.003 IU/mL/(IU/kg), respectively 2.

At 6-month assessment in adolescent or adult patients with the same dose, the mean ± SD AUC (FVIII:C) and Cmaxnorm were 16.86 ± 6.12 h·IU/mL/(IU/kg) and 0.021 ± 0.003 IU/mL/(IU/kg), respectively 2.

Volume of distribution

It is observed that simoctocog alfa is mainly distributed in the intravascular compartment.

At initial assessment following administration of 50 IU/kg simoctocog alfa in adolescent or adult patients with severe haemophilia A, the mean ± SD volume of distribution at steady state is 59.75 ± 19.76 mL/kg 2. The value in pediatric patients was 67.18 ± 13.27 mL/kg 2.

At 6-month assessment in adolescent or adult patients with the same dose, the value was 56.90 ± 9.07 mL/kg 2.

Protein binding

Circulating simoctocog alfa binds to endogenous von Willebrand factor endogenously present in the circulation 2.

Metabolism
Not Available
Route of elimination

In a non-bleeding state, simoctocog alfa is assumed to be cleared by low-density lipoprotein receptor-related protein (LRP) and low-density lipoprotein receptor (LDLR) as expected of endogenous factor VIII. In cases of bleeding or surgery, simoctocog alfa is believed to be consumed at the bleeding site as expected of factor VIII 2.

Half life

At initial assessment following administration of 50 IU/kg simoctocog alfa in adolescent or adult patients with severe haemophilia A, the mean terminal half-life (T1/2) was 17.05 ± 11.23 h 2. The mean T1/2 in pediatric patients was 12.50 ± 4.17 h 2.

At 6-month assessment in adolescent or adult patients with the same dose, the value was 14.05 ± 4.70 h 2.

Clearance

At initial assessment following administration of 50 IU/kg simoctocog alfa in adolescent or adult patients with severe haemophilia A, the mean clearance rate (CL) was 2.96 ± 0.97 mL/h/kg 2. The mean CL in pediatric patients was 4.73 ± 1.87 mL/h/kg 2.

At 6-month assessment in adolescent or adult patients with the same dose, the value was 3.39 ± 1.42 mL/h/kg 2.

Toxicity

Simoctocog alfa is not expected to cause any adverse effects on the human reproductive functions or the human fetus. As genotoxicity studies and carcinogenicity studies are not applicable for recombinant products, such studies were not performed.

According to the single-dose toxicity study in rats, there were no deaths or notable life-threatening changes to the treatment and the highest non-lethal intravenous dose was determined to be < 10,000 IU/kg 2. In a repeated-dose toxicity study in monkeys, there was no evidence of systemic toxicity. There were no observable local reactions at the injection sites based on the findings of a rabbit local tolerance study 2.

Although the formation of neutralizing antibodies (inhibitors) to FVIII is a specified warning/precaution of simoctocog alfa treatment, there have been no cases of inhibitior development throughout clinical studies 2.

No cases of overdose have been reported with simoctocog alfa 2.

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

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Lieuw K: Many factor VIII products available in the treatment of hemophilia A: an embarrassment of riches? J Blood Med. 2017 Jun 15;8:67-73. doi: 10.2147/JBM.S103796. eCollection 2017. [PubMed:28670147]
  2. Nuwiq Product Monograph [Link]
External Links
PubChem Substance
347910409
FDA label
Download (725 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
Not AvailableRecruitingNot AvailableHemophilia1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
KitIntravenous1000 [iU]/2.5mL
KitIntravenous2000 [iU]/2.5mL
KitIntravenous250 [iU]/2.5mL
KitIntravenous2500 [iU]/2.5mL
KitIntravenous3000 [iU]/2.5mL
KitIntravenous4000 [iU]/2.5mL
KitIntravenous500 [iU]/2.5mL
Kit; powder, for solutionIntravenous
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 September 17, 2015 14:59 / Updated on July 13, 2019 00:52