EU/3/07/496

On 22 October 2007, orphan designation (EU/3/07/496) was granted by the European Commission to Only for Children Pharmaceuticals, France, for mercaptopurine (oral liquid) for the treatment of acute lymphoblastic leukaemia.

What is acute lymphoblastic leukaemia?

Acute lymphoblastic 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. Acute lymphoblastic leukaemia is a cancer of certain white blood cells called lymphocytes. In this disease the lymphocytes multiply continuously 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 also replace the normal white cells, red cells and platelets in the bone marrow, which causes anaemia, easy bleeding and bruising, and infections. It is the most common type of leukaemia in young children. This disease also affects adults, especially those aged 65 years and older. Many people with acute leukaemia can be cured; however, despite the available treatments, acute lymphoblastic leukaemia remains a serious and life threatening condition in a subgroup of patients.

What are the methods of treatment available?

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 patient's age, symptoms, and general health. The primary treatment of acute lymphoblastic leukaemia 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.

Mercaptopurine is already authorised in the European Union for the treatment of this condition, in a different pharmaceutical form.
The sponsor has submitted satisfactory argumentation to justify the assumption that mercaptopurine (oral liquid) might be of potential significant benefit for the treatment of acute lymphoblastic leukaemia, mainly because its administration in children will be easier and more precise dosing could be achieved. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain orphan status.

What is the estimated number of patients affected by the condition*?

Based on the information provided by the sponsor and previous knowledge of the Committee, acute lymphoblastic leukaemia was considered to affect 0.6 in 10,000 persons in the European Union, which, at the time of designation, corresponded to about 30,000 persons.

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed based on data from the European Union (EU 27), Norway, Iceland and Lichtenstein. This represents a population of 498,000,000 (Eurostat 2006). This estimate is based on available information and calculations presented by the sponsor at the time of the application.

How is this medicinal product expected to act?

Mercaptopurine is a drug that decreases the action of a enzyme (a protein, called HGPRTase, which speeds up a specific chemical reaction in the cells). This enzyme is necessary for cell growth and replication. There are many biochemical effects of mercaptopurine, and although it is not known which of these mechanisms is more important, mercaptopurine is particularly toxic to cells that are rapidly dividing, such as cancer cells (including leukaemia cells).

What is the stage of development of this medicinal product?

At the time of submission of the application for orphan designation, no clinical trials in patients with acute lymphoblastic leukaemia had been initiated.

Mercaptopurine was authorised in the European Union, in different pharmaceutical forms from mercaptopurine (oral liquid), for the treatment of acute lymphoblastic leukaemia at the time of submission of the application.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 12 September 2007 a positive opinion recommending the grant of the above-mentioned designation.

Opinions on orphan medicinal products designations are based on the following cumulative criteria:

• 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.