EU/3/03/176: Orphan designation for the treatment of chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia is a disease in which cancer cells are found in the blood and the bone marrow. The bone marrow is the spongy tissue inside the large bones in the body. Normally, the bone marrow makes cells called 'blasts' that mature into several different types of blood cells that have specific functions in the body. These include red cells, white cells and platelets. Red blood cells carry oxygen and other materials to all tissues of the body. White blood cells fight infection. Platelets support blood clotting. When leukaemia develops, the bone marrow produces large numbers of abnormal blood cells.

There are several types of leukaemia. Chronic lymphocytic leukaemia is a cancer of the white blood cells called lymphocytes. The lymphocytes multiply too quickly and live 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 cells, red cells and platelets in the bone marrow.

Chronic lymphocytic leukaemia is the most common type of leukaemia. It mainly affects older people and is rare in people under the age of 40. Chronic lymphocytic leukaemia is chronically debilitating and life-threatening due to the severe prognosis and the poor long-term survival for high-risk patients.

At the time of designation, chronic lymphocytic leukaemia affected approximately 4 in 10,000 people in the European Union (EU). This was equivalent to a total of around 153,000 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. At the time of designation, this represented a population of 382,800,000 (Eurostat 2003).

Treatment for leukaemia is complex and depends on a number of factors including the type of leukaemia, the extent of the disease and whether the leukaemia has been treated before. It also depends on the age, the symptoms, and the general health of the patient. Some people with chronic lymphocytic leukaemia do not have treatment if their illness is not causing any symptoms and is progressing only very slowly. Treatment is only started if and when the symptoms become troublesome.

Currently, the main treatment for chronic lymphocytic leukaemia is chemotherapy (using drugs to kill cancer cells). Several products were authorised for the condition in the Community at the time of submission of the application for orphan drug designation. Recombinant antibody derivative against human CD19 and CD3 could be of potential significant benefit for the treatment of chronic lymphocytic leukaemia because it may act in a different way to other available medicines. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

Antibodies are proteins in the body that target specific shapes on the surface of foreign bodies, such as bacteria or cancer cells. Recombinant antibody derivative against human CD19 and CD3 is an antibody that is thought to bind both to leukaemia cells (that display a protein called CD19 on their surface) as well as to cells of the immune system called T lymphocytes (that display CD3). By binding these two types of cells at the same time, it is thought that this antibody may help the body's immune system to attack and kill the cancer cells.

The effects of recombinant antibody derivative against human CD19 and CD3 have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials in patients with chronic lymphocytic leukaemia had been initiated.

Recombinant antibody derivative against human CD19 and CD3 was not marketed anywhere worldwide for chronic lymphocytic leukaemia or designated as orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted a positive opinion on 10 October 2003 recommending the granting of this designation.

• the seriousness of the condition;
• the existence or not of alternative methods of diagnosis, prevention or treatment;
• either the rarity of the condition (considered to affect not more than five in ten thousand persons in the Community) or the insufficient return of development investments.

Designated orphan medicinal products are still-investigational products, which are considered for designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of the quality, safety and efficacy will be necessary before this product can be granted a marketing authorisation.