EU/3/07/453: Orphan designation for the treatment of haemophilia B (congenital factor IX deficiency)

Haemophilia B is an inherited blood disorder where the body's ability to control blood clotting (coagulation) is impaired. Patients suffering from this condition have an in-born deficiency of coagulation factor IX, which is one of the enzymes (proteins that speed up the conversion of certain substances into other substances) that help to stabilise the blood clot by mechanically linking certain big molecules to one another and thereby increasing the strength of blood clots. In affected individuals, the blood clot is not strong enough, resulting in longer bleeding time and poor wound healing in case of injury or surgery. Bleedings may also occur into muscles or joint spaces of the elbows, knees and ankles. Recurrent bleedings in the same location may lead to permanent injury of the joint. Rare, but life-threatening bleedings may occur in the central nervous system, throat or gastro-intestinal tract. Haemophilia B is chronically debilitating and may be life threatening.

At the time of designation, haemophilia B affected approximately 0.2 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 10,000 people, and is below the ceiling for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed based on data from the European Union (EU 27), Norway, Iceland and Lichtenstein. This represents a population of 498,000,000 (Eurostat 2006). This estimate is based on available information and calculations presented by the sponsor at the time of the application.

Several products to treat haemophilia B (congenital factor IX deficiency) have been authorised in member states of the European Union. These products contain different levels of factor IX and aim to replace or increase the level of the deficient enzyme. Satisfactory argumentation has been submitted by the sponsor to justify the assumption that the medicinal product recombinant fusion protein consisting of human coagulation factor IX attached to the Fc domain of human IgG1 might be of potential significant benefit for the treatment of haemophilia B, because it may provide a major contribution to patient care. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

Recombinant fusion protein consisting of human coagulation factor IX attached to the Fc domain of human IgG1 is a synthetic construct of the coagulation factor IX and a part from IgG antibodies (proteins that are part of the immune system). When given to a patient with haemophilia B, it is expected that the product replaces the deficient enzyme and shortens and decreases the bleedings into the surrounding tissues.. It is thought that this product is more stable than pure factor IX and therefore patients could potentially be treated less frequently with this product than with currently available products.

The effects of recombinant fusion protein consisting of human coagulation factor IX attached to the Fc domain of human IgG1 were evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with haemophilia B were ongoing.

Recombinant fusion protein consisting of human coagulation factor IX attached to the Fc domain of human IgG1 was not authorised anywhere worldwide for treatment of haemophilia B nor designated as orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 12 April 2007 recommending the granting of this designation.

• the seriousness of the condition;
• the existence of alternative methods of diagnosis, prevention or treatment;
• either the rarity of the condition (affecting not more than 5 in 10,000 people in the EU) or insufficient returns on investment.

Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy is necessary before a product can be granted a marketing authorisation