EU/3/05/272: Orphan designation for the treatment of acute myeloid leukaemia

Acute 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 leukaemia. 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. Leukaemia can be acute (when it develops quickly with many blasts). Acute myeloid leukaemia is life-threatening.

At the time of designation, acute myeloid leukaemia affected approximately 0.7 in 10,000 people in the European Union (EU). This was equivalent to a total of around 33,000 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 age, the symptoms, and the general health of the patient. The primary treatment of acute myeloid leukaemia is chemotherapy (using drugs to kill cancer cells) Several products were authorised for the condition in the Community at the time of submission of the application for orphan drug designation. Histamine dihydrochloride in combination with existing treatment could be of potential significant benefit for the treatment of acute myeloid leukaemia because it might improve the long-term outcome of the patients. The assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

It is not completely understood how histamine dihydrochloride works. It is suggested by the sponsor that it only acts together with another medicinal product (interleukin 2). Together they cause the destruction of the tumour cells through specific cells of the human defence system (the so-called 'natural killer' cells).

The effects of histamine dihydrochloride have been evaluated in experimental models.

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

Histamine dihydrochloride was not marketed anywhere worldwide for acute myeloid leukaemia at the time of submission. Orphan designation of histamine dihydrochloride had been granted in the United States for the use as an adjunct to cytokine therapy in the treatment of acute myeloid leukaemia.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 3 March 2005 recommending the granting of this designation.

Update: Histamine dihydrochloride (Ceplene) was authorised in the EU on 7 October 2008. Ceplene maintenance therapy is indicated for adult patients with acute myeloid leukaemia in first remission concomitantly treated with interleukin-2 (IL-2). The efficacy of Ceplene has not been fully demonstrated in patients older than age 60.

• the seriousness of the condition;
• the existence or not of alternative methods of diagnosis, prevention or treatment;
• 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 have been 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.