EU/3/10/847: Orphan designation for the treatment of haemophilia A

Haemophilia A is an inherited bleeding disorder that is caused by the lack of a substance called factor VIII. Factor VIII is one of the proteins involved in the blood coagulation (clotting) process. Patients with haemophilia A 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 A is a debilitating disease that is life-long and may be life threatening because bleeding can also happen in the brain, the spinal cord, the joints or the gut.

At the time of designation, haemophilia A affected approximately 0.6 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 30,000 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 27), Norway, Iceland and Liechtenstein. This represents a population of 506,500,000 (Eurostat 2010).

At the time of submission of the application for orphan drug designation, medicines containing factor VIII were authorised in the EU for the treatment of haemophilia A, to replace the missing protein.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with haemophilia A because it 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.

Pegylated B-domain-deleted sequence-modified recombinant human factor VIII is expected to work in the body in the same way as human factor VIII. When injected into the patient's vein, it is expected to replace the missing factor VIII, thereby correcting the deficiency and making the patient less prone to bleeding.

The medicine contains factor VIII, which is made by a method known as 'recombinant DNA technology': it is made by a cell that has received a gene (DNA) that makes the cell able to produce it. It has also been modified by a process called 'pegylation'. This means that a chemical called 'polyethylene glycol' has been attached to the factor VIII. This is expected to decrease the rate at which the substance is removed from the body, allowing the medicine to be given less often.

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 A had been started.

At the time of submission, this medicine was not authorised anywhere in the EU for haemophilia A 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 8 December 2010 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.