EU/3/15/1599: 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 life-long debilitating disease that may be life threatening because it can lead to bleeding in the brain and spinal cord and from the throat and 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 512,900,000 (Eurostat 2015).

At the time of 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 produce 'inhibitors' (antibodies) against factor IX and thereby stop the factor IX medicine from working. 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. Early studies in experimental models showed that treatment with the medicine resulted in sustained production by the body of factor IX and restoration of its activity. 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 virus that has been modified to contain the gene for factor IX, which is lacking in patients with haemophilia B. After being given once to the patient as an injection into a vein, the virus is expected to carry the factor-IX gene into the liver cells, enabling them to produce the missing factor IX for a long period. This is expected to control the bleeding disorder.

The type of virus used in this medicine ('adeno-associated virus') does not cause disease in humans.

The effects of the 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, the medicine was not authorised anywhere in the EU for haemophilia B. Orphan designation of the medicine had been granted in the United States for haemophilia B.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 12 November 2015 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.