EU/3/05/293: Orphan designation for the treatment of 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 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. It is the most common type of leukaemia in young children. This disease also affects adults, especially those aged 65 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.

At the time of designation, acute lymphoblastic leukaemia affected approximately 1.1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 51,000 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 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.
Satisfactory argumentation has been submitted by the sponsor to justify the assumption that nelarabine might be of potential significant benefit for the treatment of acute lymphoblastic 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 orphan status.

Enzymes are proteins produced by the human body that speed up the conversion of certain substances into other substances. Once in the blood, an enzyme naturally present in the body, converts nelarabine in a substance called arabinofuranosylguanine (ara-G). Ara-G is incorporated in the human genetic material (DNA) of the cancer cell and might lead to induce the so-called programmed cell death (apoptosis), which is an important process for the natural death of cells. Thus, it is believed that nelarabine could trigger cancer cell death in patients with acute lymphoblastic leukaemia.

The effects of nelarabine were evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with acute lymphoblastic leukaemia were ongoing.

Nelarabine was not marketed anywhere worldwide for acute lymphoblastic leukaemia, at the time of submission.

Orphan designation of acute lymphoblastic leukaemia was granted in the United States for treatment of acute lymphoblastic leukaemia and lymphoblastic lymphoma.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 12 May 2005 recommending the granting of this designation.

Update: Nelarabine (Atriance) has been authorised in the EU since 22 August 2007 for the treatment of patients with T-cell acute lymphoblastic leukaemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens. Due to the small patient populations in these disease settings, the information to support these indications is based on limited data.

• 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.