EU/3/14/1319: Orphan designation for the treatment of haemophilia B

Haemophilia B is an inherited bleeding disorder that is caused by the lack of factor IX, which is one of the proteins involved in the blood coagulation (clotting) process. Patients with haemophilia B are more prone to bleeding than normal and have poor wound healing after injury or surgery. Bleeding can also happen within muscles or the spaces in the joints, such as the elbows, knees and ankles. This can lead to permanent injury if it happens repeatedly.

Haemophilia B is a debilitating disease that is life long and may be life threatening because bleeding can also happen in the brain and spinal cord, the throat or the gut.

At the time of designation, haemophilia B affected approximately 0.2 in 10,000 people in the European Union (EU). This was 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 on the basis of data from the European Union (EU 28), Norway, Iceland and Liechtenstein. This represents a population of 511,100,000 (Eurostat 2014).

At the time of submission of the application for orphan drug designation, medicines containing factor IX were authorised in the EU for the treatment of haemophilia B, to replace the missing protein. However, not all patients with haemophilia B could benefit from these medicines because the immune system (the body's natural defences) can react against them by producing 'inhibitors' (antibodies) against factor IX. In these cases, other treatments needed to be used, such as factor VIIa (the activated form of factor VII, another protein involved in blood clotting), either alone or as part of a combination treatment.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with haemophilia B because it could be used in patients who have developed inhibitors against factor IX. The medicine is also expected to last longer inside the body and thus may be given less often than existing treatments. These assumptions will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine is made of a copy of human factor VIIa, to which a chain made of three copies of a fragment of the 'human chorionic gonadotropin' (hCG) hormone has been added. In the body, the medicine is expected to work in the same way as human factor VIIa. Factor VIIa is involved in blood clotting. It activates another factor called factor X, which starts the clotting process. By activating factor X, this medicine is expected to control the bleeding disorder in patients who have developed inhibitors to factor IX because it acts directly on factor X, independently of factor IX.

Attaching the hCG chain to factor VIIa is expected to decrease the rate at which the factor VIIa is cleared from the body, allowing injections to be given less frequently than medicines that contain only factor VII or VIIa.

The medicine is made by a method known as 'recombinant DNA technology': it is made by cells into which a gene (DNA) has been introduced that makes them able to produce factor VIIa linked to a chain made of fragments of hCG.

The effects of this medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with the medicine in patients with haemophilia B had been started.

At the time of submission, this medicine was not authorised anywhere in the EU for haemophilia B. Orphan designation of the medicine had been granted in the United States for the treatment and prophylaxis of bleeding episodes in patients with haemophilia A or B with inhibitors.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 10 July 2014 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.