The only recombinant therapy for congenital FXIII A-subunit deficiency1

Previous treatments for congenital FXIII A-subunit deficiency were limited to plasma-derived products accompanied by the risk of infectious-agent contamination.2,3 But Tretten® is recombinant, so it is made without human- or animal-derived products.1

Tretten® displays the same pharmacodynamic properties as human FXIII when it binds with the body's FXIII B-subunit, and has been shown to effectively prevent bleeding through once-monthly, low-volume prophylaxis.1,a

The Medical and Scientific Advisory Council (MASAC) recommends the use of Tretten® for patients with congenital FXIII A-subunit deficiency.2

aIn patients with congenital FXIII A-subunit deficiency.

Young man, living with factor XIII A-subunit deficiency, seated on an outdoor balcony while reading


Andy has congenital FXIII deficiency


 



 

Shown to be safe and effective in clinical trials1

Low annualized bleeding rate (ABR) observed over 52 weeks in mentor™11,b,c

  • ≈4-fold increase in FXIII activity (≈0.19 IU/mL to ≈0.77 IU/mL at 1 hour)4
  • 0.14 bleeds requiring treatment per subject-year1
  • 5 trauma-related bleeds (n=4)1 (no intracranial or severe bleeds into internal organs reported)4,b
    • The most common adverse reactions reported in clinical trials (≥1%) were headache, pain in the extremities, pain at injection site, and increase in fibrin D dimer levels

Half-life supports once-monthly dosing4

  • Provides adequate FXIII trough levels (>0.10 IU/mL) to support monthly treatment across all age groups (0.19 in mentor™1; with a 35-IU/kg dose 0.21 in mentor™4)4,5,c,d
  • No dose adjustment required for pediatric patients (aged 1 to <6 years) as found in mentor™41,5


b
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug may not reflect the rates observed in practice.
cData from a multicenter, multinational, open-label, single-arm, multiple-dosing, phase 3 prophylaxis trial evaluating the efficacy and safety of Tretten® for bleeding prevention in patients with congenital FXIII A-subunit deficiency. Patients aged ≥6 years weighing ≥20 kg (N=41) received monthly intravenous (IV) doses of Tretten® 35 IU/kg over a 52-week treatment period. Efficacy was measured as the mean annualized frequency of bleeding events requiring treatment with FXIII-containing products during the Tretten®prophylaxis treatment period versus the historical bleeding rate in patients with congenital FXIII deficiency treated on demand.4
d
Data from a multicenter, multinational, open-label, nonrandomized trial investigating the pharmacokinetic properties and safety profile of Tretten® in patients with congenital FXIII A-subunit deficiency. Children aged 1 to <6 years weighing ≥10 kg (N=6) were each given a single 35-IU/kg IV dose of Tretten® after a 4-week washout period of their previous prophylactic treatment. Pharmacokinetic results were measured from a comparison of the area under the concentration value with the 30-day time curve. Safety assessments included post-dose adverse event occurrence and development of neutralizing and non-neutralizing antibodies.5


 



 

Convenient once-monthly, low-volume infusion1,a

With up to 15 times less volume per infusion, Tretten® takes under 2 minutes once every 28 days to infuse—less than 26 minutes per year1,6

Up to 15x less volumee

Tretten®1

Plasma-derived FXIII concentrate6

Up to 7x faster infusione

Tretten®1

Plasma-derived FXIII concentrate6


e
Dosages based on a 70-kg person infusing 35 IU/kg from a nominally 2500-IU vial of Tretten® at 2 mL/minute or 40 IU/kg from a 1300-IU vial of plasma-derived FXIII concentrate at 4 mL/minute.


 



 

Dosing1

  • Tretten® is available in single-use vials containing nominally 2500 IU (2000 IU to 3125 IU) of lyophilized powder
  • The recommended dose for routine prophylaxis for bleeding in patients with congenital FXIII A-subunit deficiency is 35 IU/kg body weight, administered as a once-monthly IV bolus injection
    • No dose adjustment is required for pediatric patients (aged 1 to < 6 years), as found in mentor™4
    • If adequate coverage is not achieved with a 35 IU/kg dose, consider dose adjustment to reach a target trough level ≥10% using a validated assay
    • For smaller doses requiring less than a full vial, further dilute Tretten® with 0.9% sodium chloride—discard remaining product


 



 

Storage

Before reconstitution

Refrigerate at 36°F to 46°F—do not freeze—and keep away from direct light until ready for reconstitution.1

After reconstitution

Use immediately—however, storage at room temperature (up to 77°F) or in a refrigerator (do not freeze) for up to 3 hours is acceptable if necessary. After 3 hours, discard any reconstituted Tretten®.1


 



 

Tretten®—purely because they are one in a million7

The only recombinant
therapy for congenital FXIII
A-subunit deficiency1

Proven efficacy and safety in clinical trials1,f

Convenient once-monthly,
low-volume prophylaxis1,a


f
Tretten® showed a statistically significant lower ABR compared with the historical control of on-demand treatment (0.14 vs 1.68 bleeds, respectively).1


 



 

Novo Nordisk Representative


 



 

References: 1. Tretten [package insert]. Plainsboro, NJ: Novo Nordisk Inc; 2014. 2. National Hemophilia Foundation. MASAC recommendation regarding the use of recombinant clotting factor products with respect to pathogen transmission. http://www.hemophilia.org/sites/default/files/document/files/masac-226.pdf. Approved April 13, 2014. Adopted May 6, 2014. Accessed January 28, 2016. 3. National Hemophilia Foundation. MASAC recommendations concerning products licensed for the treatment of hemophilia and other bleeding disorders. http://www.hemophilia.org/sites/default/files/document/files/230Text2014-09.pdf. Approved September 20, 2014. Adopted September 21, 2014. Accessed January 28, 2016. 4. Inbal A, Oldenburg J, Carcao M, Rosholm A, Tehranchi R, Nugent D. Recombinant factor XIII: a safe and novel treatment for congenital factor XIII deficiency. Blood. 2012;119(22):5111-5117. 5. Williams M, Will A, Stenmo C, Rosholm A, Tehranchi R. Pharmacokinetics of recombinant factor XIII in young children with congenital FXIII deficiency and comparison with older patients. Haemophilia. 2014;20(1):99-105. 6. Corifact [package insert]. Kankakee, IL: CSL Behring LLC; 2013. 7. Kohler HP, Ichinose A, Seitz R, Ariens RAS, Muszbek L; Factor XIII and Fibrinogen SSC Subcommittee of the ISTH. Diagnosis and classification of factor XIII deficiencies. J Thromb Haemost. 2011;9(7):1404-1406.

Selected Important Safety Information

Tretten® is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients.

Tretten® may cause allergic reactions. If signs or symptoms of anaphylaxis or hypersensitivity reactions (including urticaria, rash, tightness of the chest, wheezing, hypotension) occur, discontinue immediately and institute appropriate treatment.

Indications and Usage

Tretten® (Coagulation Factor XIII A-Subunit [Recombinant]) is indicated for routine prophylaxis of bleeding in patients with congenital Factor XIII A-subunit deficiency.

Tretten® is not for use in patients with congenital Factor XIII B-subunit deficiency.

Important Safety Information

Tretten® is contraindicated in patients with hypersensitivity to the active substance or to any of the exicipients.

Tretten® may cause allergic reactions. If signs or symptoms of anaphylaxis or hypersensitivity reactions (including urticaria, rash, tightness of the chest, wheezing, hypotension) occur, discontinue immediately and institute appropriate treatment.

Thromboembolic complications may occur. Monitor patients with conditions that predispose to thrombosis for signs and symptoms of thrombosis after administration of Tretten®.

Inhibitory antibodies may occur with Tretten®. Patients with inhibitory antibodies may manifest as an inadequate response to treatment. If expected plasma FXIII activity levels are not attained, or if breakthrough bleeding occurs while receiving prophylaxis, perform an assay that measures FXIII inhibitory antibody concentrations.

The most common adverse reactions reported in clinical trials (≥1%) were headache, pain in the extremities, pain at injection site, and increase in fibrin D dimer levels. 

Thrombosis may occur if Tretten® is administered concomitantly with Factor VIIa.

There are no adequate and well-controlled studies using Tretten® in pregnant women to determine whether there is a drug-associated risk. Animal reproduction studies have not been conducted with Tretten®.

Please click here for Tretten® Prescribing Information.