EU/3/12/1091: 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 carry 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 severe 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 intermedia and major affected approximately 1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 51,000 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. At the time of designation, this represented a population of 512,200,000 (Eurostat 2013).

At the time of designation, the main treatments for beta thalassaemia intermedia and major were blood transfusion and the use of iron chelators (medicines for reducing 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 patients because, as a gene therapy, it offers the possibility of curing the genetic defect in the bone marrow cells that cause beta thalassaemia in contrast to transfusion and iron chelators, which only manage the effects of the disease. 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 that carries normal copies of the beta-globin gene into the cells. When these modified cells are transplanted back into the patient, they are expected to develop into healthy red blood cells that produce 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 (a 'lentivirus') is modified so that it does not cause disease in humans.

The effects of the medicinal product have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with the medicinal product in patients with beta thalassaemia intermedia and major had been started.

At the time of submission, the medicinal product was not authorised anywhere in the EU for beta thalassaemia intermedia and major or designated as an orphan medicinal product elsewhere for these conditions.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 6 December 2012 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.