EU/3/09/623: Orphan designation for the treatment of beta thalassaemia intermedia and major

Beta thalassaemia is an inherited disease in which patients are unable to make enough haemoglobin, the protein found in red blood cells that carries oxygen around the body. Beta thalassaemia major is a severe form of the disease in which patients need frequent blood transfusions. Beta thalassaemia intermedia is a less severe form, which may get worse with age.
Beta thalassaemia intermedia and major are caused by abnormalities in a gene that is responsible for the production of beta globin. Beta globin is one of the proteins that make up haemoglobin.
Beta thalassaemia intermedia and major are debilitating diseases that are long lasting and may be life threatening because of the anaemia (the lack of haemoglobin), the need for repeated blood transfusions and the risk of complications associated with them.

At the time of designation, beta thalassaemia major and intermedia affected approximately 1 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 50,000 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 designation, blood transfusion was used to treat the symptoms of beta thalassaemia intermedia and major. This was usually combined with iron chelators, medicines used to reduce the high iron levels in the body caused by repeated blood transfusions.
In some cases, bone marrow transplantation was used to cure the disease. This is a complex procedure in which the bone marrow of the patient is destroyed and replaced with bone marrow from a matched donor, to allow the patient to produce red blood cells with normal levels of haemoglobin.
The sponsor has provided sufficient information to show that this medicine might be of significant benefit for the patients, particularly because it may represent an alternative to bone marrow transplantation. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine is made up of 'haematopoietic stem cells' that are taken from the patient. Haematopoietic stem cells are cells that can develop into different types of blood cell. To make this medicine, the cells are modified by a virus so that they contain normal copies of the beta-globin gene. When these modified cells are transplanted back into the patient, they are expected to start producing beta globins that can be assembled into haemoglobin, avoiding the need for blood transfusion or bone marrow transplantation. The type of virus used in this medicine ('lentivirus') is modified so that it does not cause disease in humans.

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 in patients with beta thalassaemia intermedia or major had been started.
At the time of submission, this medicine was not authorised anywhere in the EU for beta thalassaemia intermedia and major. Orphan designation of this medicine had been granted in United States of America for these conditions.
In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 4 March 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.