EU/3/04/192: Orphan designation for the treatment of myelodysplastic syndromes

Myelodysplastic syndromes are a distinct group of disorders in which the production of blood cells by the bone marrow is abnormal. The bone marrow is the spongy tissue found in the large bones. It has the function of producing red cells (which are the main carriers of oxygen to body tissues), white blood cells (which fight infection), and platelets (which make the blood clot). In myelodysplastic syndromes these cells do not grow and mature normally. Consequently, several symptoms can develop: fatigue or weakness (due to anaemia, red-cell deficit), infections (due to an decrease in white blood cells) or easy bruising or abnormal bleeding (platelet deficit). Myelodysplastic syndromes are life-threatening because they can result in severe anaemia, infections or haemorrhage and they can progress to acute leukaemia.

At the time of designation, myelodysplastic syndromes affected between 1 and 3 in 10,000 people in the European Union (EU). This was equivalent to a total of around 46,000 to 139,000 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 25), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 464,200,000 (Eurostat 2004).

At the time of submission of the application for orphan-drug designation, there were no treatments authorised in the European Union. Available therapeutic options for myelodysplastic syndromes included supportive care methods (e.g. antibiotics to treat infections, blood or platelet transfusions for anaemia or bleeding respectively), the use of products such as erythropoietin (a substance that stimulates the bone marrow to produce red cells), chemotherapy (using drugs that can kill the abnormal cells), and bone-marrow transplantation.

3-(4'Aminoisoindoline-1'-one)-1-piperidine-2,6-dione mechanism of action is quite complex and only partly understood.

This substance acts at different levels: by modulating the immune system activity, by stimulating the growth of red blood cells (thus reducing the anaemia), and by inhibiting the growth of new blood vessels.

The effects of 3-(4'aminoisoindoline-1'-one)-1-piperidine-2,6-dione have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with myelodysplastic syndromes were ongoing.

The medicinal product was not marketed anywhere worldwide for myelodysplastic syndromes designated as an orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 5 February 2004 recommending the granting of this designation.

Update: 3-(4'aminoisoindoline-1'-one)-1-piperidine-2,6-dione (Revlimid) was authorised in the EU on 13 June 2013 for the treatment of patients with transfusion-dependent anaemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate.

• 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.