EU/3/07/516

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', which mature into several different types of blood cell 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 should develop into a type of white blood cell called granulocytes are affected. The blasts do not mature, and become too many. These blast cells are then found in the blood. They also accumulate in the bone marrow where they take the place of the other types of normal blood cells, causing anaemia, easy bruising, and frequent infections. Myeloid 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 2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 100,000 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 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 500,300,000 (Eurostat 2007).

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.

Satisfactory argumentation has been submitted by the sponsor to justify the assumption that recombinant human histone H1.3 and recombinant human N-bis-met-histone H1.3 might be of potential significant benefit for the treatment of acute myeloid leukaemia because of its mechanism of action, which is different from that of existing treatments. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

Histones including histone H1.3 are naturally occurring proteins of the human body where they predominantly occur in the nucleus of cells. Recombinant N-bis-met-histone H1.3 is an artificial molecule (a prodrug) which is transformed in the body to histone H1.3. Tumour cells differ from healthy cells as their outer membrane bear receptors (proteins that bind specific molecules), which bind histone H1.3 and N-bis-met-histone H1.3. These histones and the receptors form large aggregates in the membrane, leading to membrane ruptures and the ultimate death of the cancer cells.

The effects of recombinant human histone H1.3 and recombinant human N-bis-met-histone H1.3 have been 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.

Recombinant human histone H1.3 and recombinant human N-bis-met-histone H1.3 was not authorised anywhere worldwide for the treatment of acute myeloid leukaemia, at the time of submission.

Orphan designation of amonafide l-malate was granted in the United States for 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 8 November 2007 recommending the granting of this designation.

• 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.