EU/3/09/622: Orphan designation for the treatment of acute myeloid leukaemia

Acute myeloid leukaemia (AML) is a cancer of the white blood cells (cells that fight against infections). In patients with AML, the bone marrow (the spongy tissue inside the large bone) produces large numbers of abnormal, immature white blood cells called 'blasts'. These abnormal cells quickly build up in large numbers in the bone marrow and are found in the blood.

AML is a life-threatening disease because these immature cells take the place of the normal white blood cells, reducing the patient's ability to fight infections.

At the time of designation AML affected less than 2 in 10,000 people in the European Union (EU)*. This is equivalent to a total of fewer than 101,000 people, and is below the threshold for orphan designation, which is 5 in 10,000. This is based on the information provided by the sponsor and 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. This represents a population of 504,800,000 (Eurostat 2009).

Treatment for AML is complex and depends on a number of factors including the extent of the disease, whether it has been treated before, and the patient's age, symptoms and general state of health. The primary treatments of AML are chemotherapy (medicines to treat cancer) and bone marrow transplantation (a complex procedure where the bone marrow of the patient is destroyed and replaced with bone marrow from a matched donor).

The sponsor has provided sufficient information to show that N-(5-tert-Butylisoxazol-3-yl)-N'-{4-[7-(2-(morpholin-4-yl)ethoxy) imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea di-hydrochloride salt might be of significant benefit for the treatment of AML, mainly because it works in a different way to other medicines and may be used in combination with other treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine is a chemically produced substance that is expected to work by blocking a protein called receptor tyrosine kinase. This protein can be found on the surface of the cancerous cells in AML, and is involved in stimulating the cell to grow and divide uncontrollably. The medicine blocks the receptor tyrosine kinase of the type FLT3. By blocking this receptor, the medicine is expected to control the division of the cancerous cells and slow down the development of the disease.

The effects of N-(5-tert-Butylisoxazol-3-yl)-N'-{4-[7-(2-(morpholin-4-yl)ethoxy) imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea di-hydrochloride salt have been evaluated in experimental models.

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

At the time of submission, this medicine was not authorised anywhere in the EU for treatment of AML or designated as orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 9 February 2009 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 5 five in 10,000 people in the Community) 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 marketing authorisation.