Congenital Factor Xiii Recombinant For Clotting Disorder
The U.S. Food and Drug Administration on 23rd December 2013 approved Tretten, Coagulation Factor XIII A-Subunit (Recombinant), the first recombinant product for use in the routine prevention of bleeding in adults and children who have a rare clotting disorder, known as congenital Factor XIII A-subunit deficiency. Human Factor XIII (FXIII) is a pivotal factor for the formation of blood clots. In the absence of Factor XIII, loose clots are formed, leading to bleeding complications.
Tretten was developed by Novo Nordisk; a global healthcare company headquartered in Denmark, with 90 years of experiencein drug development and holds a leading position in Haemophilia care, growth hormone therapy and hormone replacement therapy.
Congenital Factor XIII deficiency is an extremely rare genetic disorder thatcausessevere bleeding due to the absence of the clotting factor.Patients with congenital FXIII A-subunit deficiency have a lifelong susceptibility towards bleeding, including spontaneous intracranial hemorrhage.The incidence is 1 in a million to 1 in 5 million people. This disease is mostly caused due to mutations in the A subunit gene which is located on chromosome 6p25-p24. This mutation is inherited as an autosomal recessive fashion.As Factor XIII is composed of two subunits,A and B, for which the genes are located on different chromosomes, administration of recombinant A subunit improves clot stability and thusbecomes a therapeutic option for patients with this condition.
Tretten is a recombinant analogue of the human Factor XIII A-subunit. This drugis manufactured as an intracellular, soluble protein in yeast strain Saccharomyces cerevisiae. The proteinis subsequently isolated by homogenization of cells and purified by several chromatographic methods, including hydrophobic interaction and ion exchange chromatography.Finally, it is sterile freeze-dried into powder form to be reconstituted with a diluent and injected intravenously. It is available as a white lyophilized powder in single-use vial containing nominally 2500 IU per vial of recombinant coagulation factor XIII A-subunit.
The dose for routine prophylaxis for bleeding in patients with congenital factor XIII (FXIII) A-subunit deficiency is 35 international units (IU) per kilogram body weight, once monthly to achieve a target trough level FXIII activity at or above 10%, as measured using a validated assay. Tretten should not be administered along with other infusion solutions or as drip and should be administered at a rate not exceeding 2-3ml per minute.
Tretten is a protransglutaminase (Recombinant Factor XIII [rA2] homodimer) that binds to free human Factor XIII B-subunit resulting in the formation of heterotetramer [rA2B2]. It has asimilar half-life likeHuman Factor XIII subunits[A2B2]. Itis activated by thrombin in the presence of Ca2+, andfunctions in a dose-dependent manner, increasingthe mechanical strength of fibrin clots, retarding fibrinolysis, and also enhancing platelet adhesion to the site of injury. Thus, Trettenproduces the same pharmacodynamic properties in plasma as Human Factor XIII.
The FDA approval of Tretten was based on a phase III, multi-centered, open-label, non-controlledclinical trial that was conducted for 52 weeks in 41subjects. When compared to an historic control group of subjects who did not receive routine FXIII infusions, preventive treatment with monthly 35 IU/kg Tretten injections significantly decreased the number of treatment-requiring bleeding episodes.
Adverse effects associated with the use of Tretten may include headache,pain in the extremities,injection site pain,hypersensitivity reactions, and thromboembolic risks. Tretten has no other contraindications except to those who have hypersensitivity towards the active pharmaceutical ingredients.
Thus, Tretten is a boon for congenital Factor XIII A-subunit deficiency patients, as the syndrome is considered to be an orphan disease. Tretten is the only recombinant treatment for this disease which was proven safe and effective offering patients once-monthly dosing with a short infusion time.
Tretten was developed by Novo Nordisk; a global healthcare company headquartered in Denmark, with 90 years of experiencein drug development and holds a leading position in Haemophilia care, growth hormone therapy and hormone replacement therapy.
Congenital Factor XIII deficiency is an extremely rare genetic disorder thatcausessevere bleeding due to the absence of the clotting factor.Patients with congenital FXIII A-subunit deficiency have a lifelong susceptibility towards bleeding, including spontaneous intracranial hemorrhage.The incidence is 1 in a million to 1 in 5 million people. This disease is mostly caused due to mutations in the A subunit gene which is located on chromosome 6p25-p24. This mutation is inherited as an autosomal recessive fashion.As Factor XIII is composed of two subunits,A and B, for which the genes are located on different chromosomes, administration of recombinant A subunit improves clot stability and thusbecomes a therapeutic option for patients with this condition.
Tretten is a recombinant analogue of the human Factor XIII A-subunit. This drugis manufactured as an intracellular, soluble protein in yeast strain Saccharomyces cerevisiae. The proteinis subsequently isolated by homogenization of cells and purified by several chromatographic methods, including hydrophobic interaction and ion exchange chromatography.Finally, it is sterile freeze-dried into powder form to be reconstituted with a diluent and injected intravenously. It is available as a white lyophilized powder in single-use vial containing nominally 2500 IU per vial of recombinant coagulation factor XIII A-subunit.
The dose for routine prophylaxis for bleeding in patients with congenital factor XIII (FXIII) A-subunit deficiency is 35 international units (IU) per kilogram body weight, once monthly to achieve a target trough level FXIII activity at or above 10%, as measured using a validated assay. Tretten should not be administered along with other infusion solutions or as drip and should be administered at a rate not exceeding 2-3ml per minute.
Tretten is a protransglutaminase (Recombinant Factor XIII [rA2] homodimer) that binds to free human Factor XIII B-subunit resulting in the formation of heterotetramer [rA2B2]. It has asimilar half-life likeHuman Factor XIII subunits[A2B2]. Itis activated by thrombin in the presence of Ca2+, andfunctions in a dose-dependent manner, increasingthe mechanical strength of fibrin clots, retarding fibrinolysis, and also enhancing platelet adhesion to the site of injury. Thus, Trettenproduces the same pharmacodynamic properties in plasma as Human Factor XIII.
The FDA approval of Tretten was based on a phase III, multi-centered, open-label, non-controlledclinical trial that was conducted for 52 weeks in 41subjects. When compared to an historic control group of subjects who did not receive routine FXIII infusions, preventive treatment with monthly 35 IU/kg Tretten injections significantly decreased the number of treatment-requiring bleeding episodes.
Adverse effects associated with the use of Tretten may include headache,pain in the extremities,injection site pain,hypersensitivity reactions, and thromboembolic risks. Tretten has no other contraindications except to those who have hypersensitivity towards the active pharmaceutical ingredients.
Thus, Tretten is a boon for congenital Factor XIII A-subunit deficiency patients, as the syndrome is considered to be an orphan disease. Tretten is the only recombinant treatment for this disease which was proven safe and effective offering patients once-monthly dosing with a short infusion time.
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