EU/3/08/581: 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”, which mature into several different types of blood cells with 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. Over a period of time these abnormal cells replace the normal white cells, red cells and platelets in the bone marrow, which reduces the number of normal cells in the blood and leads to anaemia, coagulation problems (bruising, haemorrhages) and repeated infections.

There are several types of leukaemias. Chronic lymphocytic leukaemia is a cancer of a type of white blood cell called the B-lymphocyte. The lymphocytes multiply 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. Chronic lymphocytic leukaemia is the most common type of leukaemia; it mainly affects older people, being 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 3.5 in 10,000 people in the European Union (EU). This was equivalent to a total of around 176,000 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 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, symptoms, and the general health of the patient. Some people with B-cell chronic lymphocytic leukaemia never have treatment, if their illness is not causing any symptoms and is progressing slowly. Treatment is often started only if and when the symptoms become troublesome. Current main treatment of 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.

Ofatumumab could be of potential significant benefit for the treatment of chronic lymphocytic leukaemia, because it might act differently from other medicinal products. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

Ofatumumab is a monoclonal antibody. A monoclonal antibody is an antibody (a type of protein) that has been designed to recognise and bind to a specific structure (called an antigen) that is found on certain cells in the body.

Ofatumumab has been designed to target an antigen called CD20, which is present on the surface of all B-lymphocytes. When ofatumumab binds to the antigen, this causes lysis (cell death). This is expected to help in chronic lymphocytic leukaemia by destroying the cancerous B-lymphocytes.

The effects of ofatumumab were evaluated in experimental models.

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

Ofatumumab was not authorised 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 COMP adopted a positive opinion on 10 September 2008 recommending the granting of this designation.

Update: Ofatumumab (Arzerra) has been authorised in the EU since 19 April 2010 for the treatment of chronic lymphocytic leukaemia (CLL) in patients who are refractory to fludarabine and alemtuzumab.

• 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 European Union) 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.