EU/3/14/1300: 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, while beta thalassaemia intermedia is a less severe form, which may worsen with age.

Both beta thalassaemia intermedia and major are caused by defects in the gene responsible for the production of beta-globin, one of the components of haemoglobin, which result in low or no production of beta-globin.

Beta thalassaemia intermedia and major are long-lasting 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 major and minor 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 28), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 512,900,000 (Eurostat 2014).

At the time of designation, the main treatments for beta thalassaemia intermedia and major were blood transfusions 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 with beta thalassaemia intermedia or major because early studies show that it may improve anaemia, an aspect of the condition that is not targeted by currently authorised treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

In patients with beta-thalassemia, the bone marrow has too many precursor red blood cells that fail to develop into mature red blood cells.

This medicine is an engineered protein that has been designed to attach to certain proteins in the body which slow down (or inhibit) the maturation of red blood cells. By attaching to these 'inhibitory' proteins, it is expected to trap them so they do not have their normal effect on the red blood cells. As a result, production of red blood cells is increased. This is expected to improve the symptoms of patients with beta thalassaemia intermedia and major.

The effects of the medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with beta thalassaemia intermedia and major were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for beta thalassaemia intermedia and major. Orphan designation of the medicine had been granted in the United States for beta thalassaemia.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 12 June 2014 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.