EU/3/05/304: Orphan designation for the treatment of acute lymphoblastic leukaemia

Acute lymphoblastic leukemia 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 leukemia develops, the bone marrow produces large numbers of abnormal blood cells. There are several types of leukemias. Acute lymphoblastic leukemia is a cancer of certain white blood cells called lymphocytes. In this disease the lymphocytes multiply too quickly and live too long, so there are too many of them circulating in the blood. These leukaemic lymphocytes look normal, but they are not fully developed and do not work properly. Over a period of time these abnormal cells replace the normal white cells, red cells and platelets in the bone marrow. Acute lymphoblastic leukemia is the most common type of leukemia in young children. This disease also affects adults, especially those aged 65 and older. Many patients with acute leukemia can be cured. However, despite the available treatments, acute lymphoblastic leukemia remains a serious and life threatening condition in a subgroup of patients.

At the time of designation, acute lymphoblastic leukaemia affected approximately 0.5 in 10,000 people in the European Union (EU). This was equivalent to a total of around 23,000 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 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 patient's age, symptoms, and general health. The primary treatment of acute lymphoblastic leukemia is chemotherapy (using drugs to kill cancer cells) followed or combined with radiotherapy (using high-energy x-rays or other types of high-energy rays to kill cancer cells). Bone marrow transplantation is also available.

The sponsor has provided sufficient information to show that imatinib mesilate might be of significant benefit for patients with acute lymphoblastic leukemia because 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 acute lymphoblastic leukaemia were ongoing.

Imatinib mesilate was not marketed anywhere worldwide for acute lymphoblastic leukaemia, 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 13 July 2005 recommending the granting of this designation.

Update: Imatinib mesilate (Glivec) has been authorised in the EU since 13 September 2006 for the treatment of adults patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) integrated with chemotherapy.

• 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