EU/3/05/320: Orphan designation for the treatment of chronic eosinophilic leukaemia and the hypereosinophilic syndrome

Chronic eosinophilic leukaemia is a disease in which cancer cells are found in the blood, the bone marrow and in tissues. 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 leukaemia develops, the bone marrow produces large numbers of abnormal blood cells. There are several types of leukaemias. In chronic eosinophilic leukaemia, blasts that are developing into white blood cells called eosinophils are affected. The eosinophils become too numerous and are then found in the bone marrow, blood and in other tissues such as the heart, lungs, nerves and skin. The excess of eosinophils in tissues can cause disturbances in the function and thereby damage the affected organs. In many cases, it is impossible to find the origin of the cancer cells and then the disease is called hypereosinophilic syndrome. The disease can develop very slowly, which is why it is called chronic. Chronic eosinophilic leukaemia and the hypereosinophilic syndrome are life-threatening.

At the time of designation, chronic eosinophilic leukaemia and the hypereosinophilic syndrome affected less than 1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 47,000 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).

No satisfactory methods existed that were authorised at the time of application.

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 chronic eosinophilic leukaemia and the hypereosinophilic syndrome were ongoing.

Imatinib mesilate was not marketed anywhere worldwide for chronic eosinophilic leukaemia and the hypereosinophilic syndrome, 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 19 August 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 hypereosinophilic syndrome (HES) and chronic eosinophilic leukaemia (CEL).

• 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.