Identification
- Summary
Simoctocog alfa is an antihemorrhagic agent used for the treatment and prophylaxis of bleeding in patients of all ages with haemophilia A (congenital factor VIII deficiency).
- Brand Names
- Nuwiq
- Generic Name
- Simoctocog alfa
- DrugBank Accession Number
- DB09108
- Background
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.
- Type
- Biotech
- Groups
- Approved
- 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
- Simoctocog alfa
Pharmacology
- Indication
Simoctocog alfa is a recombinant antihemophilic factor [blood coagulation factor VIII (Factor VIII) indicated in adults and children with Hemophilia A for the on-demand treatment and control of bleeding episodes, perioperative management of bleeding, and routine prophylaxis to reduce the frequency of bleeding episodes. It is not indicated for the treatment of von Willebrand Disease.3,4
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Prophylaxis of Bleeding caused by hemophilia a •••••••••••• Management of Bleeding caused by hemophilia a •••••••••••• Management of Bleeding caused by hemophilia a •••••••••••• - Associated Therapies
- Contraindications & Blackbox Warnings
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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.
Target Actions Organism Avon Willebrand factor bindingHumans - 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.
- Adverse Effects
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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.
- 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.Not Available
- Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Nuwiq Injection, powder, for solution 2000 IU Intravenous Octapharma Ab 2021-01-12 Not applicable EU 
Nuwiq Injection, powder, for solution 250 IU Intravenous Octapharma Ab 2021-01-12 Not applicable EU Nuwiq Injection, powder, for solution 1500 IU Intravenous Octapharma Ab 2022-05-04 Not applicable EU Nuwiq Kit 1000 [iU]/2.5mL Intravenous Octapharma USA Inc 2016-01-01 Not applicable US 
Nuwiq Kit 3000 [iU]/2.5mL Intravenous Octapharma USA Inc 2017-08-01 Not applicable US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Nuwiq Simoctocog alfa (4000 unit / vial) + Water (2.5 mL / syr) Kit; Powder, for solution Intravenous Octapharma Pharmazeutika Produktionsges M B H 2018-07-25 Not applicable Canada 
Nuwiq Simoctocog alfa (2000 unit / vial) + Water (2.5 mL / syr) Kit; Powder, for solution Intravenous Octapharma Pharmazeutika Produktionsges M B H 2015-12-22 Not applicable Canada Nuwiq Simoctocog alfa (1500 unit / vial) + Water (2.5 mL / syr) Kit; Powder, for solution Intravenous Octapharma Pharmazeutika Produktionsges M B H Not applicable Not applicable Canada Nuwiq Simoctocog alfa (3000 unit / vial) + Water (2.5 mL / syr) Kit; Powder, for solution Intravenous Octapharma Pharmazeutika Produktionsges M B H 2018-07-25 Not applicable Canada Nuwiq Simoctocog alfa (500 unit / vial) + Water (2.5 mL / syr) Kit; Powder, for solution Intravenous Octapharma Pharmazeutika Produktionsges M B H 2015-12-22 Not applicable Canada
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- 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
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- U50VWW6XH6
- CAS number
- 1219013-68-9
References
- General References
- 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. [Article]
- Nuwiq Product Monograph [Link]
- EMA Summary of Product Characteristics: Nuwiq (simoctocog alfa) Intraveous Injection [Link]
- FDA Approved Drug Products: NUWIQ [Antihemophilic Factor (Recombinant)] Lyophilized Powder for Solution for Intravenous Injection [Link]
- External Links
- PubChem Substance
- 347910409
- 1729084
- Wikipedia
- Factor_VIII_(medication)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Not Yet Recruiting Treatment Hemophilia A 1 4 Recruiting Treatment Severe Hemophilia A 1 3 Withdrawn Prevention Hemophilia A 1 2 Recruiting Treatment Hemophilia A With Inhibitors 1 Not Available Completed Not Available Hemophilia 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, for solution Intravenous 1000 IU Injection, powder, for solution Intravenous 1500 IU Injection, powder, for solution Intravenous 2000 IU Injection, powder, for solution Intravenous 2500 IU Injection, powder, for solution Intravenous 3000 IU Injection, powder, for solution Intravenous 4000 IU Kit Intravenous 1000 [iU]/2.5mL Kit Intravenous 1500 [iU]/2.5mL Kit Intravenous 2000 [iU]/2.5mL Kit Intravenous 250 [iU]/2.5mL Kit Intravenous 2500 [iU]/2.5mL Kit Intravenous 3000 [iU]/2.5mL Kit Intravenous 4000 [iU]/2.5mL Kit Intravenous 500 [iU]/2.5mL Kit; powder, for solution Intravenous Injection, powder, lyophilized, for solution Intravenous 1000 IU Injection, powder, lyophilized, for solution Intravenous 2000 IU Injection, powder, for solution Intravenous Injection, powder, for solution Intravenous 250 IU Injection, powder, for solution Intravenous 500 IU - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- 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 at September 17, 2015 20:59 / Updated at March 11, 2022 14:12