EU/3/09/723: 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 human proteins involved in the blood 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 if bleeding happens in the brain, spinal cord, throat or gut.

At the time of designation, haemophilia B affected approximately 0.1 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 5,000 people, and is below the threshold for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and 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 27), Norway, Iceland and Liechtenstein. This represents a population of 504,800,000 (Eurostat 2009).

At the time of submission of the application for orphan designation, medicines containing factor IX were authorised in the EU for the treatment of haemophilia B. These medicines replace the missing protein. In some patients, other treatments were also needed, such as medicines containing other substances involved in blood clotting such as factor VIIa.

The sponsor has provided sufficient information to show that recombinant fusion protein linking human coagulation factor IX with human albumin might be of significant benefit for patients with haemophilia B because the medicine is expected to be given less often than currently used treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

The medicine is made of a copy of human factor IX, which is attached to albumin, a protein that acts as a carrier. In the body, the medicine is expected to replace the missing factor IX, making the patient less prone to bleeding. Attaching albumin to factor IX is expected to decrease the rate at which the factor IX is cleared from the body, allowing more time between injections than for medicines that contain only factor IX.

The medicine is made by a method known as 'recombinant DNA technology': it is made by a cell that has received a gene (DNA) that makes it able to produce factor IX linked to albumin.

The effects of recombinant fusion protein linking human coagulation factor IX with human albumin have been evaluated in experimental models.

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

At the time of submission, recombinant fusion protein linking human coagulation factor IX with human albumin was not authorised anywhere in the EU for haemophilia B or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 3 December 2009 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 Community) 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.