EU/3/08/569: 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 leukaemic lymphocytes look normal, but they are not fully developed and do not work properly. Over a period of time, these abnormal cells replace the normal white and red blood cells and platelets in the bone marrow (the spongy tissue inside the large bones in the body that produces blood cells). ALL is the most common type of leukaemia in young children but the disease also affects adults, especially those aged 65 and older. Many people with acute leukaemia can be cured. However, despite the available treatments, ALL remains a serious and life-threatening condition in some patients.

At the time of designation, ALL affected approximately 0.7 in 10,000 people in the European Union (EU). This was equivalent to a total of around 35,000 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. At the time of designation, this represented a population of 502,800,000 (Eurostat 2008).

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. The main treatment is chemotherapy (medicines used to kill cancer cells) followed by or combined with radiotherapy (using radiation to kill cancer cells). Bone-marrow transplantation is also used.

The sponsor has provided sufficient information to show that pegylated L-asparaginase might be of potential significant benefit for the treatment of ALL because it is a new formulation of L-asparaginase that is given less often than conventional forms of the medicine. It is also expected to increase the medicine's tolerability by decreasing the response of the immune system to the L-asparaginase. These assumptions will have to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine consists of L-asparaginase that has been 'pegylated' (coated with a chemical called polyethylene glycol or PEG). This reduces the rate at which it is cleared from the body and reduces the interaction between L-asparaginase and the immune system.

L-asparaginase is an enzyme that breaks down the substance L-asparagine in the blood. L-asparagine is produced by the normal cells in the human body. Certain cancer cells, such as the cancerous cells in ALL, cannot make L-asparagine, so they need take it up from the blood in order to grow. By reducing the levels of L-asparagine in the blood, the cancerous ALL cells are deprived of their supply of L-asparagine and die.

The effects of pegylated L-asparaginase have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials in patients with pegylated L-asparaginase had been started.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 9 July 2008 recommending the granting of this orphan designation.

• the seriousness of the condition;
• the existence of alternative methods of diagnosis, prevention or treatment;
• and 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.