EU/3/06/370: 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 leukaemias. 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 less than 1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 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 28), Norway, Iceland and Liechtenstein. This represents a population of 512,200,000 (Eurostat 2013).

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.

Decitabine might be of potential significant benefit for the treatment of acute myeloid leukaemia, because it may act in a different way than other medicines, which might potentially be easier to use in the older patient population. The assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

Decitabine is a chemical substance, which is related to cytidine. Cytidine is part of the fundamental genetic material of cells (DNA and RNA). Decitabine blocks (inhibits) the building up (synthesis) of DNA and thereby could inhibit the growth of tumour cells.

The effects of decitabine were evaluated in experimental models.

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

Decitabine was not authorised anywhere worldwide for acute myeloid leukaemia, at the time of submission. Orphan designation of decitabine was granted in the European Union and in the United States for treatment of myelodysplastic syndromes.

In accordance with to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted a positive opinion on 5 April 2006 recommending the granting of the above-mentioned designation.

Update: Decitabine (Dacogen) was authorised in the EU on 20 September 2012 for treatment of adult patients aged 65 years and above with newly diagnosed de novo or secondary acute myeloid leukaemia (AML), according to the World Health Organization (WHO) classification, who are not candidates for standard induction chemotherapy.

• 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 that are considered for designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy will be necessary before this product can be granted a marketing authorisation.