EU/3/09/650: 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, acute lymphoblastic leukaemia affected approximately 1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 50,000 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 healthy bone marrow from a matched donor.

The sponsor has provided sufficient information to show that blinatumomab might be of significant benefit for patients with ALL because it works in a different way to existing treatments and preliminary studies indicate that it may be an alternative to existing treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Blinatumomab is a monoclonal antibody (a type of protein) that has been designed to specifically recognise and attach to the following proteins:

• CD19, a protein that is found on the surface of ALL cells;
• the 'T-cell-receptor/CD3 complex', which is responsible for the activation of some cells of the immune system (the body's natural defences) called T cells.

By attaching to the cancer cells and the T-cell-receptor/CD3 complex, the medicine is expected to stimulate the T cells to kill the cancer cells.

The effects of blinatumomab have been evaluated in experimental models.

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

At the time of submission, blinatumomab was not authorised anywhere in the EU for ALL. Orphan designation of blinatumomab had been granted in the United States for ALL.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 2 June 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 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.