EU/3/14/1328: 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 bones, where blood cells are produced) produces large numbers of abnormal, immature white blood cells. These abnormal cells quickly build up in large numbers in the bone marrow and are found in the blood.

AML is a long-term debilitating and life-threatening disease because these abnormal immature cells take the place of the normal white blood cells, causing bleeding episodes, blood clots and reducing the patient's ability to fight infections.

At the time of designation, AML affected approximately 1.2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 61,000 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 511,100,000 (Eurostat 2014).

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. At the time of designation, the main treatments for AML were chemotherapy (medicines to treat cancer) and haematopoietic (blood) stem-cell transplantation (a complex procedure where the patient receives stem cells from a matched donor to help restore the bone marrow).

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with AML because results of early studies showed improvements in patients with previously untreated and advanced disease. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine works by blocking the action of a protein known as MDM2. MDM2 normally regulates the action of a cancer-suppressing protein called p53 which prevents cancer by promoting cell death and repair.

In many cancers MDM2 is overactive, leading to reduced p53 activity. By attaching to MDM2 and blocking its action, this medicine is expected to increase the activity of p53 and restore the body's ability to prevent the growth of the cancer cells.

The effects of the medicine have been evaluated in experimental models.

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

At the time of submission, the medicine was not authorised anywhere in the EU for AML. Orphan designation of the medicine had been granted in the United States for the treatment of this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 10 July 2014 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.