EU/3/09/628: Orphan designation for the treatment of acute lymphoblastic leukaemia

Acute lymphoblastic leukaemia (ALL) is a cancer of the white blood cells called lymphocytes. In this disease, the lymphocytes multiply too quickly and live for too long, so there are too many of them circulating in the blood. These abnormal lymphocytes are not fully developed and do not work properly. Over a period of time, they replace the normal white cells and red blood cells and platelets in the bone marrow (the spongy tissue inside the large bones in the body).

ALL is the most common type of leukaemia in young children, but the disease also affects adults, especially those aged 65 years and older. Many people with ALL can be cured. However, despite the available treatments, ALL remains a serious and life-threatening disease in some patients.

At the time of designation, ALL 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 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 504,800,000 (Eurostat 2009).

Treatment for ALL 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 treatment of ALL was chemotherapy (medicines used to kill cancer cells) followed by or combined with radiotherapy (using radiations to kill cancer cells). Bone-marrow transplantation was also used. This is 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 mercaptopurine (oral suspension) might be of significant benefit for the patients because of the way in which the medicine is given. Mercaptopurine is already available in the European Union as tablets for the treatment of ALL. Mercaptopurine (oral suspension) is a liquid form of mercaptopurine, which could be given to children who have difficulty swallowing tablets. This may make it easier for children to take the medicine and allow the dose to be adjusted more precisely according to the patient's weight. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Mercaptopurine (oral suspension) is expected to work in the same way as mercaptopurine tablets.

Mercaptopurine is an anticancer medicine that belongs to the group 'antimetabolites'. It works by interfering with the production of DNA within cells, preventing them from making more copies of their DNA. This means that cancer cells cannot divide and eventually die.

At the time of submission of the application for orphan designation, a 'bioequivalence' study in adults had been planned, to find out whether the oral suspension of mercaptopurine was treated by the body in the same way as the tablets.

At the time of submission, mercaptopurine (oral suspension) was not authorised anywhere in the EU for ALL 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 4 March 2009 recommending the granting of this designation.

Update: Mercaptopurine (oral suspension) (Xaluprine) was authorised in the EU on 9 March 2012 for the treatment of acute lymphoblastic leukaemia (ALL) in adults, adolescents and children.

• 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 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 a marketing authorisation.