EU/3/16/1650: 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 iron-rich 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, while beta thalassaemia intermedia is a less severe form, which may get worse with age. Both types of beta thalassaemia are caused by defects in the gene responsible for the production of beta globin, one of the components of haemoglobin, which result in low levels of haemoglobin in the blood.

Beta thalassaemia intermedia and major are life-long debilitating diseases. They may be life threatening because of severe anaemia (low red blood cell count due to 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 0.5 in 10,000 people in the European Union (EU). This was equivalent to a total of around 26,000 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 513,700,000 (Eurostat 2016).

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, allogeneic haematopoietic (blood) stem cell transplantation was used to cure the disease. This is a complex procedure where the bone marrow of the patient is cleared of cells and replaced with healthy bone marrow cells from a matched donor, allowing the patient to produce red blood cells with normal haemoglobin.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients because early data in experimental models suggest it may decrease the amount of excess iron that builds up in the body following repeated transfusions in patients with the condition. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

In patients with beta thalassaemia intermedia or major, excess iron can build up in the body following repeated transfusions and damage organs such as the heart and liver. This medicine is a small protein fragment that mimics the action of the hormone hepcidin, which is able to regulate the levels of iron in the body. Hepcidin reduces the amount of iron in the blood by blocking absorption of iron from food and by stopping the release of iron from iron-storage cells. The medicine is therefore expected to correct the iron overload and prevent organ damage due to iron accumulation in patients with beta thalassaemia intermedia or major.

At the time of submission of the application for orphan designation, the evaluation of the effects of the medicine in experimental models was ongoing.

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

At the time of submission, the medicine was not authorised anywhere in the EU for beta thalassaemia intermedia and major 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 23 March 2016 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.