NOVOTHIRTEEN (catridecacog)

Key points

Favourable opinion for reimbursement in long-term prophylaxis of bleeding in patients with congenital Factor XIII A-subunit deficiency.

What therapeutic improvement?

No clinical added value compared to FIBROGAMMIN human plasma-derived factor XIII.

Role in the care pathway?

Therapeutic management is based on fresh frozen plasma and on FIBROGAMMIN human plasma-derived FXIII concentrate.

Bleeding episodes can be treated with factor XIII concentrate or, otherwise, with frozen fresh plasma.

Prophylactic replacement therapy with factor XIII concentrate is generally initiated in all diagnosed patients, often from the first inaugural bleeding episode, to prevent the most frequent and most serious bleeding, more particularly intracranial bleeding, which can occur spontaneously from childhood. In the absence of prophylaxis during pregnancy, the risk of spontaneous miscarriage is very high.

In practice, the use of fresh frozen plasma (FFP) is limited - and very rarely used prophylactically - as long-term treatment due to the long duration of the injections and the risk of volume overload and allergic reactions (large number of substances in addition to factor XIII). The advantages of FIBROGAMMIN compared to FFP are the FXIII concentration (62.5 IU/mL versus 1 IU/ml in FFP) making it possible to administer smaller volumes, the high degree of viral safety ensured by pasteurisation, and the good tolerance of the concentrate.

Role of the medicinal product in the care pathway

NOVOTHIRTEEN (catridecacog) is an alternative to the only FXIII concentrate currently available, FIBROGAMMIN, for the long-term prophylaxis of bleeding in patients with congenital Factor XIII A-subunit deficiency. Both are administered once monthly.

NOVOTHIRTEEN (catridecacog) is the first recombinant FXIII concentrate and therefore offers the advantage of a higher degree of safety compared to blood-derived products, such as FIBROGAMMIN, which expose patients to a potential risk of transmission of infectious diseases.

In addition, this recombinant FXIII is significantly more concentrated than the plasma-derived FXIII (FIBROGAMMIN) available (833 IU/ml versus 62.5 IU/ml after reconstitution), enabling the injection of a smaller volume and administration as a bolus injection. However, given this high concentration, for young children weighing less than 24 kg it is necessary to dilute the solution after reconstitution to allow the necessary dose to be taken, and consequently to use another volume calculation formula to be taken to that used in patients with a higher bodyweight.

It should be highlighted that NOVOTHIRTEEN (catridecacog) is only intended for the management of patients with FXIII A-subunit deficiency, unlike FIBROGAMMIN, which is also indicated in patients with B-subunit deficiency. Although A-subunit deficiency is largely more common (around 95% of cases), it is necessary to identify the type of subunit missing before using catridecacog to ensure that this concentrate is appropriate. This identification is currently not systematic across in all centres treating these patients.

The Committee recalls that, in accordance with the SPC, the data are very limited in pregnant women. Consequently, it considers that the use of NOVOTHIRTEEN (catridecacog) should only be considered if duly justified and following multidisciplinary discussion.