Drug name (Brand / Generic)
Corifact in US, Fibrogammin in other countries
Corifact is an intravenous drug indicated for the treatment of bleeding disorder in patients with factor XIII deficiency. It has been developed and is being manufactured by CSL Behring of Germany.
The drug received orphan drug designation in January 1985. The Biologics License Agreement was submitted in August 2010 under the accelerated approval regulation. The drug was approved by the US FDA in February 2011.
It is the first and the only XIII concentrate approved in the US. The approval was based on a pivotal study conducted on 14 patients including children and adults.
The drug is being marketed in 12 countries apart from the US under the trade name fibrogammin.
Factor XIII deficiency is the rarest form of Haemophilia and is caused due to the deficiency of factor XIII (fibrin stabilising factor deficiency) in blood. Factor XIII is necessary for the blood clotting and its deficiency may lead to severe bleeding. The disease can be caused due to ancestral inheritance.
In a factor XIII deficient patient, blood clotting takes place but the clots get disintegrated easily. The clot breaks, leading to further bleeding. The bleeding usually occurs due to trauma. Bleeding from the umbilical cord is the first symptom of the congenital bleeding disorder.
Other symptoms include poor wound healing, miscarriages, subcutaneous bleeding and excessive bleeding in joints.
Factor XIII is a transglutaminase enzyme which is required for clotting of blood and is activated by the calcium ions or the thrombin cleavage. It enhances the cross linking of fibrin chains during the coagulation of blood and prevents fibrinolysis that results in the removal of small blood clots. The absence of factor XIII leads to delayed clotting and severe bleeding.
Corifact is a factor XIII freeze dried concentrate prepared from the human plasma collected from healthy donors. It contains the subunits A and B.
Factor XIII is activated by the calcium ions and is then converted into factor XIIIA enzyme. This enzyme enhances the linking of the fibrin molecules. The cross linking converts the loose fibrin molecule to a tougher one with higher tensile strength.
The concentrate is first dissolved in sterile water provided during purchase and then injected intravenously. The drug acts as a substitute to the missing factor XIII and thereby prevents and corrects bleeding disorder.
More than 12 studies were conducted in patients with congenital factor XIII deficiency. Around 187 patients were recruited, of which 90 were aged under 16.
The patients were administered 40 units/kg dose of the recombinant factor XIII. The primary end point of the trials was to achieve an increase in factor XIII levels by more than 5% every 28 days.
A Phase I study was conducted in factor XIII deficient patients in 1997. Another Phase I trial was initiated to evaluate the safety of the drug in 12 congenital factor XIII deficient patients in February 2003.
Phase II trials to study the safety and efficacy of the drug in 15 patients were initiated in May 2009 and completed by April 2010. The patients were administered three doses of 40 units/kg of factor XIII every 28 days.
A Phase III trial was initiated in August 2009 to study the efficacy of the drug in treating the factor XIII deficient patients. Around 41 patients were enrolled and administered corifact every 28 days.
Patients who did not participate in the pharmacokinetic study were administered 40 units/kg dose intravenously. The primary outcome measure of the study was to determine the spontaneous bleeding events which require treatment.
A Phase III trial to determine the safety of recombinant factor XIII in patients with factor XIII deficiency was initiated in September 2009 in Europe, Asia and US. Around 60 patients have been enrolled.
The primary outcome measure is to determine the adverse affects of the drug and the secondary outcome measure is to evaluate the antibody and inhibitor development. The entire study is expected to be completed by May 2013.
Another Phase III trial to evaluate the safety and pharmacokinetics of the drug in children aged one to six was initiated in November 2010. Six children have been enrolled and will be administered a single intravenous dose of corifact. The trial is expected to be completed by January 2012.
A Phase III trial to evaluate the long term safety of the drug in European, Asian and US patients was initiated in January 2011.
Six children aged one to six with congenital factor XIII deficiency have been enrolled. The primary outcome measure is to assess the various adverse and non-adverse reactions in the patients. The study is scheduled for completion in December 2013.
A Phase IV study was initiated in August 2009 to evaluate the clinical efficacy of the drug.
The trial will also compare the incidence of bleeding in patients undergoing treatment to that of the patients without treatment. The trial has recruited around 41 patients. The entire study is expected to be completed by December 2011.
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