EU/3/06/375: Orphan designation for the treatment of chronic myeloid leukaemia

Chronic myeloid leukemia (CML) is a disease 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 leukemia develops, the bone marrow produces large numbers of abnormal blood cells. There are several types of leukemias. In myeloid leukemia 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 leukemia. Chronic myeloid leukemia is life-threatening.

At the time of designation, chronic myeloid leukaemia affected approximately 1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 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 468,900,000 (Eurostat 2006).

Treatment for leukemia is complex and depends on a number of factors including the type of leukemia, the extent of the disease and whether the leukemia has been treated before. It also depends on the age, the symptoms, and the general health of the patient. At the time of submission of the application for orphan drug designation authorised treatments of chronic myeloid leukemia included chemotherapy agents (using drugs to kill cancer cells) and immunotherapy agents (using drugs that stimulate the body's own immune system to kill cancer cells). Sometimes a combination of immunotherapy and chemotherapies were used. Another product is also used which blocks (inhibits) growth signals within cancer cells and prevents a series of chemical reactions that cause the cell to grow and divide thus stopping cancer cells to grow. Bone marrow transplantation was also used.

Nilotinib could be of potential significant benefit for the treatment of chronic myeloid leukaemia mainly because it might improve the long-term outcome of the 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 transformation of certain substances into other substances. Nilotinib blocks (inhibits) a certain class of enzymes called tyrosine kinases. These enzymes play a role in a cascade of molecular reactions that bring a certain signal from outside the cell into the cell thereby controlling the growth of cells. In chronic myeloid leukaemia, the function of these enzymes is disturbed causing uncontrolled growth and multiplication of the cancer cells. Nilotinib might, by inhibition of one or more of these enzymes activity, at certain levels in the cascade, help in slowing down or stopping the further growth of the cancer cells.

The effects of nilotinib 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.

Nilotinib was not authorised anywhere worldwide for chronic myeloid leukaemia or designated as 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 April 2006 recommending the granting of this designation.

Update: Nilotinib (Tasigna) has been authorised in the EU for the treatment of adult patients with newly diagnosed Philadelphia chromosome positive chronic myelogenous leukaemia (CML) in the chronic phase.

More information on Tasigna can be found in the European public assessment report (EPAR) on the Agency's website.

• 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.