catridecacog; - Tretten; NovoThirteen; rFXIII; Factor XIII, recombinant
Status - BLA approved in Dec. 2013
Cross ref.: See also Corifact, a plasma-derived Factor XIII product
Organizations involved:
Novo Nordisk A/S – Manuf.; R&D; Tech; USA mark.
Novo Nordisk Pharmaceuticals, Inc. – USA mark.
ZymoGenetics, Inc. - R&D; Tech.; Former.
Description: This is a formulation of recombinant, yeast-expressed, human Factor XIII subunit A. The calculated molecular formula is C3708H5735N1013O1111S28.
Nomenclature: catridecacog [INN]; Factor XIII, rDNA [BIO]; Tretten [FDA]; human Factor XIII [A2] homodimer (allele F13A*1B), recombinant DNA origin [CAS]; rFXIII [SY]; NovoThirteen [SY]
Approved in the EU, Switzerland, & Australia as NovoThirteen.
Biology: Factor XIII deficiency patients need exogenous subunit A of factor XIII since they have a mutation which prevents production of the A subunit. Deficiency leads to defective cross-linking of fibrin and vulnerability to late re-bleeds when the primary hemostatic plug is overwhelmed. However, since the B-subunit is located on a separate chromosome, factor XIII deficient patients actually produce the B-subunit normally. When these two subunits interact in the plasma, the enzyme is activated and can act within the clotting cascade. rFXIII acts by inhibiting fibrinolysis factors which enzymatically cleave the fibrin matrix, leading to the ultimate formation of clots. Administration of recombinant A subunit improves clot stability.
Companies.: Developed and manufactured by Novo Nordisk A/S. Marketing in the U.S. by Novo Nordisk Pharmaceuticals, Inc.
Novo Nordisk licensed rFXIII from ZymoGenetics, Novo Nordisk paid ZymoGenetics $15 million upon signing, and pays up to $62 million in additional milestone payments. Novo Nordisk will also pay a royalty to ZymoGenetics on any products containing recombinant Factor XIII, including combinations with Factor VIIa, marketed by Novo Nordisk as NovoSeven.
FDA class: Biologic BLA
Status: The BLA was filed in Feb. 23, 2011. Approval was essentially denied, a "complete response" letter issued, citing manufacturing issues, in Feb. 2012. A second letter citing continuing manufacturing issues was issued in Aug. 2013.
The company had originally anticipated filing its marketing authorization application to the European Medicines Agency in Q2 2011, but this apparently remains in hold.
Trials: Results from a Phase III trial examining the efficacy and safety of rFXIII for the prevention of bleeds associated with congenital FXIII deficiency showed that when compared to a historic control group of individuals who did not receive routine FXIII infusions, preventive treatment with monthly recombinant FXIII injections significantly decreased the number of bleeding episodes requiring treatment. These data were presented at the American Society of Hematology (ASH) meeting in December 2010, and marked the first completed Phase III study conducted to study the use of a recombinant FXIII treatment to prevent bleeding episodes in congenital FXIII deficiency patients. In the trial, 41 patients were observed over one year, with rFXIII administered as a preventive, once-monthly replacement therapy for FXIII congenital deficiency. Over the course of the treatment period, a total of five bleeding episodes, all associated with trauma and requiring additional FXIII treatment, were observed in four patients. Additionally, no thromboembolic events or fatal adverse events were reported.
Disease: With an estimated 600 diagnosed patients worldwide, and about 150 in the U.S., FXIII deficiency is considered one of the rarest bleeding disorders.
Companies involvement:
Full monograph
152.2 Factor XIII, rDNA
Nomenclature:
NovoThirteen []
Factor XIII, rDNA [BIO]
catridecacog [INN]
human Factor XIII [A2] homodimer (allele F13A*1B), recombinant DNA origin [CAS]
rFXIII [SY]
FDA Class: Biologic BLA
Year of approval (FDA) = 2013
Date of 1st FDA approval = 20131223
(in format YYYYMMDD)
Index Terms:
antihemophilic factors
biopharmaceutical products
blood products
octoxynol (Triton X-100)
EU000 Not yet/Never filed with EU
UM001 Marketed Product in US
US200 Currently Approved in US
EM999 Not Available/Not Marketed in EU
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