EU/3/10/742

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) 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 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. This represents a population of 506,500,000 (Eurostat 2010).

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 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 2-methoxymethyl-2-hydroxymethyl-1-azabicyclo[2,2,2]octan-3-one might be of significant benefit for patients with AML because it works in a different way to existing treatments and early studies show that it might improve the treatment of patients with this condition, particularly those who do not respond to existing treatments. These assumptions will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Some AML patients have modified forms of a protein called p53 in their cancer cells. The p53 protein is involved in causing cell death, and cancer cells carrying a modified form of the p53 protein are less able to respond to standard treatments. The exact way that 2-methoxymethyl-2-hydroxymethyl-1-azabicyclo[2,2,2]octan-3-one works in AML is not known, but it is thought to restore the normal function of the p53 protein. As a result, this medicine is expected to restore the ability of p53 to cause death of cancer cells, slowing down the progression of AML. It may also restore the ability of cancer cells to respond to other treatments.

The effects of 2-methoxymethyl-2-hydroxymethyl-1-azabicyclo[2,2,2]octan-3-one have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with 2-methoxymethyl-2-hydroxymethyl-1-azabicyclo[2,2,2]octan-3-one that included patients with AML were ongoing.

At the time of submission, 2-methoxymethyl-2-hydroxymethyl-1-azabicyclo[2,2,2]octan-3-one was not authorised anywhere in the EU for AML or designated as an orphan medicinal product elsewhere for this condition.

• 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.