EU/3/14/1298: Orphan designation for the treatment of haemophilia B

Haemophilia B is an inherited bleeding disorder that is caused by the lack of a substance called factor IX. Factor IX 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, which can lead to permanent injury if it happens repeatedly.

Haemophilia B is a debilitating disease that is lifelong 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 less than 0.2 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 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 designation, medicines containing factor IX were authorised in the EU for the treatment of haemophilia B, to replace the missing factor-IX 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 were used, such as medicines containing other coagulation factors such as factor VIIa, 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 early studies in experimental models indicate that it could be used to control bleeding episodes in haemophilia B patients who have developed inhibitors against factor IX. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine is made of a small strand of synthetic genetic material, called 'small interfering RNA' (siRNA), that has been designed to interfere with or block the gene for the protein antithrombin, thereby reducing its production. In the body, antithrombin blocks thrombin, one of the substances involved in blood clotting. By reducing the production of antithrombin, the medicine is expected to increase the clotting capacity of the blood in patients with haemophilia B.

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

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

At the time of submission, the medicine was not authorised anywhere in the EU for haemophilia B. Orphan designation of the medicine had been granted in United States for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 12 June 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.