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| Primary information |
|---|
| ID | 10829 |
| Therapeutic ID | Th1195 |
| Protein Name | Simoctocog Alfa |
| Sequence | NA
|
| Molecular Weight | 170000 |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | 14.05 ± 4.70 h |
| 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. No animal proteins are used in the purification process and no human albumin is used as a stabiliser in the manufacture of Human-cl rhFVIII. 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. |
| Indication/Disease | Treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIII deficiency). |
| Pharmacodynamics | The factor VIII/von Willebrand factor complex consists of two molecules (factor VIII and von Willebrand factor) with different physiological functions. When infused into a haemophiliac patient, factor VIII binds to von Willebrand factor in the patient’s circulation. Activated factor VIII acts as a cofactor for activated factor IX, accelerating the conversion of factor X to activated factor X. Activated factor X converts prothrombin into thrombin. Thrombin then converts fibrinogen into fibrin and a clot can be formed. Haemophilia A is a sex-linked hereditary disorder of blood coagulation due to decreased levels of factor VIII:C and results in profuse bleeding into joints, muscles or internal organs, either spontaneously or as results of accidental or surgical trauma. By replacement therapy the plasma levels of factor VIII are increased, thereby temporarily enabling a correction of the factor VIII deficiency and correction of the bleeding tendencies. |
| Mechanism of Action | NA |
| 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 [L1115]. 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 [L1115]. 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 [L1115]. No cases of overdose have been reported with simoctocog alfa [L1115]. |
| Metabolism | NA |
| 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) [L1115]. The mean ± SD maximum plasma concentration divided by the dose (Cmaxnorm) was 0.022 ± 0.003 IU/mL/(IU/kg) [L1115]. 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 [L1115]. 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 [L1115]. |
| 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 [L1115]. The value in pediatric patients was 67.18 ± 13.27 mL/kg [L1115]. At 6-month assessment in adolescent or adult patients with the same dose, the value was 56.90 ± 9.07 mL/kg [L1115]. |
| 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 [L1115]. The mean CL in pediatric patients was 4.73 ± 1.87 mL/h/kg [L1115]. At 6-month assessment in adolescent or adult patients with the same dose, the value was 3.39 ± 1.42 mL/h/kg [L1115]. |
| Categories | Antihaemorrhagics: blood coagulation factor VIII |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | von Willebrand factor |
| Brand Name | Nuwiq |
| Company | Octapharma Pharmazeutika Produktionsges M B H |
| Brand Description | Octapharma Pharmazeutika Produktionsges M B H |
| Prescribed For | NA |
| Chemical Name | human coagulation factor VIII |
| Formulation | 250 IU |
| Physical Appearance | Powder and solvent for solution |
| Route of Administration | Intravenous infusion |
| Recommended Dosage | The calculation of the required dose of factor VIII is based on the empirical finding that 1 International Unit (IU) factor VIII per kg body weight raises the plasma factor VIII activity by approximately 2% of normal activity or 2 IU/dl. |
| Contraindication | Hypersensitivity to the active substance or to any of the excipients listed in section |
| Side Effects | Hypersensitivity which may include angiooedema, burning and stinging at the infusion site, chills, flushing, generalised urticaria, headache, hives, hypotension, lethargy, nausea, restlessness, tachycardia, tightness of the chest, tingling, vomiting, wheezing |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |