EU/3/05/340: Orphan designation for the treatment of myelodysplastic / myeloproliferative diseases

Myelodysplastic / myeloproliferative diseases (MDS / MPD) are a distinct group of disorders in which cancer cells are found in the blood and in the bone marrow. The bone marrow is the spongy tissue inside the large bones in the body. Normally, the bone marrow makes cells called “blasts” that mature into several different types of blood cells that have specific functions in the body. These include red cells, white cells and platelets. Red blood cells carry oxygen and other materials to all tissues of the body. White blood cells fight infection. Platelets make the blood clot. When the disease develops, the bone marrow produces large amounts of one or several types of abnormal blood cells. Even when mature, because of their abnormality, these blood cells are not able to exercise their normal function and will lead to a variety of symptoms such as fatigue or weakness (due to anaemia, the red cells deficit), infections (due to decrease in normal white blood cells) or easy bruising or abnormal bleeding (platelet deficit). Various organs can be infiltrated by these cells and can, apart from increased size, start to malfunction because of this. MDS / MPD are life-threatening.

At the time of designation, myelodysplastic / myeloproliferative diseases affected less than 1.6 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 75,000 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 466,600,000 (Eurostat 2005).

Treatment for MDS / MPD is complex and depends on a number of factors including the type and the extent of the disease and whether this has been treated before. It also depends on the patient's age, symptoms, and general health. Current treatments for MDS / MPD include bone marrow transplantation and chemotherapy (using drugs to kill cancer cells). Some anticancer agents were authorised in the Community for the treatment of MDS / MPD at the time of submission of the application for orphan designation. Satisfactory argumentation has been submitted by the sponsor to justify the assumption that imatinib mesilate might be of potential significant benefit for the treatment of MDS / MPD, because it may act in a different way than the available methods and it might improve the long-term outcome of the patients. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Enzymes are proteins produced by the human body that speed up the conversion of certain substances into other substances. Imatinib mesilate blocks (inhibits) the enzyme tyrosine kinase. This enzyme plays a role in a cascade of molecular reactions to bring a certain signal from outside the cell into the cell thereby controlling the growth of the cells. In cancer cells, the function of this enzyme is disturbed causing uncontrolled growth and multiplication of the cancer cells. Imatinib mesilate might, by inhibition of this enzyme activity, help in slowing down or stopping the further growth of the cancer cells.

At the time of submission of the application for orphan designation, clinical trials in patients with MDS / MPD were ongoing.

Imatinib mesilate was not marketed anywhere worldwide for MDS / MPD, at the time of submission. Orphan designation of imatinib mesilate was granted in Europe and in the United States for chronic myeloproliferative leukaemia and for gastrointestinal stromal tumours.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 10 November 2005 recommending the granting of this designation.

Update: Imatinib mesilate (Glivec) has been authorised in the EU since 28 November 2006 for treatment of adult patients with myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with PDGFR gene re-arrangements.

• 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.