ATC Group: B02BD Blood coagulation factors

Factor IX is a single chain glycoprotein with a molecular mass of about 68,000 Dalton. It is a vitamin-K dependent coagulation factor and it is synthesised in the liver. Factor IX is activated by factor XIa in the intrinsic coagulation pathway and by the factor VII/tissue factor complex in the extrinsic pathway. Activated factor IX, in combination with activated factor VIII, activates factor X.

Pharmacological doses of rFVIIa activate factor X directly on the surface of activated platelets, localized to the site of injury, independently of tissue factor. This results in the conversion of prothrombin into large amounts of thrombin independently of tissue factor.

Activated factor VIII acts as a cofactor for activated factor IX, accelerating the conversion of factor X to activated factor X (factor Xa). Haemophilia A is a sex-linked hereditary disorder of blood coagulation due to decreased levels of factor VIII:C. By replacement therapy the plasma levels of factor VIII are increased, thereby enabling a temporary correction of the factor deficiency and correction of the bleeding tendencies.

Coagulation factor X is derived from human plasma and used as a replacement for the naturally existing coagulation factor X in patients with hereditary factor X deficiency.

Factor XIII connects the amino group of lysine with glutamine via its enzymatic function (transamidase activity), thereby leading to the cross-linking of fibrin molecules. This is the final stage of blood coagulation. Fibrin cross-linking and stabilisation promote the penetration of fibroblasts and support wound healing.

Eftrenonacog alfa is a long-acting, fully recombinant, fusion protein comprising human coagulation factor IX covalently linked to the Fc domain of human immunoglobulin G1, and produced by recombinant DNA technology. Haemophilia B is an X-linked hereditary disorder of blood coagulation due to decreased levels of factor IX and results in bleeding into joints, muscles or internal organs, either spontaneously or as a result of accidental or surgical trauma. By replacement therapy the plasma level of factor IX is increased thereby enabling a temporary correction of the factor deficiency and correction of the bleeding tendencies.

Etranacogene dezaparvovec is a gene therapy product designed to introduce a copy of the human Factor IX coding DNA sequence into hepatocytes to address the root cause of the Haemophilia B disease. Etranacogene dezaparvovec partially or completely ameliorates the deficiency of circulating Factor IX procoagulant activity in patients with Haemophilia B.

Fidanacogene elaparvovec is a gene therapy designed to introduce a functional copy of the high activity Padua variant of the factor IX gene (FIX-R338L) in the transduced cells to address the monogenic root cause of haemophilia B.

Lonoctocog alfa is a recombinant human protein that replaces the missing coagulation factor VIII needed for effective hemostasis. Lonoctocog alfa is a single polypeptide chain with a truncated B-domain that allows for a covalent bridge to link the factor VIII heavy and light chains. Lonoctocog alfa has demonstrated a higher VWF affinity relative to full-length rFVIII. VWF stabilizes factor VIII and protects it from degradation. Activated lonoctocog alfa has an amino acid sequence identical to endogenous FVIIIa.

Moroctocog alfa is a B-domain deleted recombinant coagulation factor VIII. Moroctocog alfa has functional characteristics comparable to those of endogenous factor VIII. Haemophilia A is a sex-linked hereditary disorder of blood coagulation due to decreased levels of factor VIII:C. By replacement therapy, the plasma levels of factor VIII are increased, thereby enabling a temporary correction of the factor deficiency and correction of the bleeding tendencies.

Nonacog alfa is a recombinant coagulation factor IX. Recombinant coagulation factor IX is a recombinant DNA-based protein therapeutic which has structural and functional characteristics comparable to endogenous factor IX. Haemophilia B is a sex-linked hereditary disorder of blood coagulation due to decreased levels of factor IX. By replacement therapy the plasma levels of factor IX is increased, thereby enabling a temporary correction of the factor deficiency and correction of the bleeding tendencies.

Octocog alfa (Full length recombinant human coagulation factor VIII (rDNA)) is a purified protein that has 2,332 amino acids. It is produced by recombinant DNA technology in baby hamster kidney cells (BHK) into which the human factor VIII gene has been introduced.

Rurioctocog alfa pegol, is a pegylated recombinant human factor VIII with an extended half-life. Rurioctocog alfa pegol is a covalent conjugate of octocog alfa consisting of 2,332 amino acids with polyethylene glycol (PEG) reagent (MW 20 kDa). The therapeutic activity of rurioctocog alfa pegol is derived from octocog alfa, which is produced by recombinant DNA technology from a Chinese hamster ovary cell line. Octocog alfa is then covalently conjugated with the PEG reagent. The PEG moiety is conjugated to octocog alfa to increase the plasma half-life.

Susoctocog alfa is a recombinant, B-domain deleted, porcine sequence Factor VIII. It is a glycoprotein. Acquired haemophilia is a rare bleeding disorder in which patients with normal Factor VIII genes develop inhibitory autoantibodies directed against Factor VIII. These autoantibodies neutralize circulating human Factor VIII thus creating a deficiency of available Factor VIII. Susoctocog alfa temporarily replaces the inhibited endogenous Factor VIII that is needed for effective haemostasis.

Valoctocogene roxaparvovec is an adeno-associated virus serotype 5 (AAV5) based gene therapy vector causing the expression of the B-domain deleted SQ form of a recombinant human factor VIII (hFVIII-SQ) under the control of a liver-specific promoter. The expressed hFVIII-SQ replaces the missing coagulation factor VIII needed for effective haemostasis.

Administration of von Willebrand factor allows correction of the haemostatic abnormalities exhibited by patients who suffer from von Willebrand factor deficiency.