EU/3/15/1585

On 14 December 2015, orphan designation (EU/3/15/1585) was granted by the European Commission to Rare Partners srl Impresa Sociale, Italy, for sirolimus for the treatment of beta-thalassaemia intermedia and major.

What is 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 types of beta thalassaemia are caused by defects in the gene responsible for producing 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.

What is the estimated number of patients affected by the condition?

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 isbased on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

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* 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).

What treatments are available?

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 ‘iron overload’ - 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 involves destruction of the patient’s bone marrow and replacing it with bone marrow from a matched donor, to allow the patient to produce healthy red blood cells with normal haemoglobin.

The sponsor has provided sufficient information to show that sirolimus might be of significant benefit for patients with beta thalassaemia intermedia and major. Sirolimus works in a different way to existing treatments and early studies in experimental models indicate that it may improve the outcome of patients with this condition by stimulating the production of a type of haemoglobin called fetal haemoglobin. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

In the womb, the baby produces a form of haemoglobin known as fetal haemoglobin but switches to adult haemoglobin at birth. However, patients with beta thalassaemia are unable to produce functional adult haemoglobin, because of their inability to produce beta-globin.

This medicine is expected to work by stimulating the bone marrow to start producing fetal haemoglobin again. As fetal haemoglobin works in the same way as the adult form, it can make up for the missing adult haemoglobin in patients with beta thalassaemia and thereby reduce the need for blood transfusions. Production of fetal haemoglobin is not compromised in beta thalassaemia patients because it does not contain beta-globin.

What is the stage of development of this medicine?

The effects of sirolimus have been evaluated in experimental models.

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

At the time of submission, sirolimus 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 12 November 2015 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:

• 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.

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.