EU/3/01/021: Orphan designation for the treatment of chronic myeloid leukaemia

Chronic myeloid leukaemia is a disease in which cancer cells are found in the blood and 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 leukaemia develops, the bone marrow produces large numbers of abnormal blood cells.

There are several types of leukaemias. In myeloid leukaemia blasts that are developing into white blood cells called granulocytes are affected. The blasts do not mature and become too many. These blast cells are then found in the blood and also accumulate in the bone marrow. The disease can develop very slowly, which is why it is called chronic myeloid leukaemia. Chronic myeloid leukaemia is life-threatening.

At the time of designation, chronic myeloid leukaemia affected approximately 0.9 in 10,000 people in the European Union (EU). This was equivalent to a total of around 34,000 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. At the time of designation, this represented a population of 378,800,000 (Eurostat 2001).

Treatment for leukaemia is complex and depends on a number of factors including the type of leukaemia, the extent of the disease and whether the leukaemia has been treated before. It also depends on the age, the symptoms, and the general health of the patient. Current treatment of chronic myeloid leukaemia is chemotherapy (using drugs to kill cancer cells) and immunotherapy (using drugs that stimulate the body's own immune system to kill cancer cells) Sometimes a combination of immunotherapy and chemotherapy may be used. Bone marrow transplantation is also used. Several treatments were authorised at the time of submission of the application for orphan drug designation

Imatinib mesilate could be of potential significant benefit for the treatment of chronic myeloid leukaemia, because it may act in a different way to other drugs and it might improve the long-term outcome of patients. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary 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 of bringing a certain external signal inside the cell itself, thereby controlling the growth of the cell. 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.

The effects of imatinib mesilate were evaluated in experimental models. At the time of submission of the application for orphan designation, clinical trials in patients with chronic myeloid leukaemia were ongoing.
Imatinib mesilate was not marketed or designated as orphan medicinal product elsewhere, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 19 December 2000 recommending the granting of this designation.

Update: Imatinib mesilate (Glivec) has been authorised in the EU since 7 November 2001 for the treatment of adult and paediatric patients with newly diagnosed Philadelphia chromosome (bcr-abl) positive (Ph+) chronic myeloid leukaemia (CML) for whom bone marrow transplantation is not considered as the first line of treatment.

Glivec is also indicated for the treatment of adult and paediatric patients with Ph+ CML in chronic phase after failure of interferon-alpha therapy, or in accelerated phase or blast crisis.

• the seriousness of the condition,
• the existence or not of alternative methods of diagnosis, prevention or treatment and
• either the rarity of the condition (considered to affect not more than five in ten thousand persons in the Community) or the insufficient return of development investments.

Designated orphan medicinal products are still investigational products, which were considered for designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of the quality, safety and efficacy will be necessary before this product can be granted a marketing authorisation.