EU/3/08/592: Orphan designation for the treatment of hairy cell leukaemia

Hairy cell leukaemia is a cancer of the blood, when too many B-lymphocytes (a type of white blood cell) are produced. The term 'hairy cell' refers to the hair-like projections that can be seen on the surface of the lymphocytes when they are examined under a microscope. In this disease, the cancerous cells build up in the blood, bone marrow and spleen. This can cause an enlarged spleen, anaemia (low red blood cell counts), leucopenia (low white blood cell counts), problems with blood clotting including bruising and bleeding, and repeated infections. Patients also have general symptoms such as weakness, weight loss and shortness of breath. Hairy cell leukaemia makes up 2% of all leukaemias.

Hairy cell leukaemia is life-threatening. Patients with this disease have poor long-term survival.

At the time of designation, hairy cell leukaemia affected less than 1 in 10,000 people in the European Union (EU) *. This is below the threshold for orphan designation, which is 5 in 10,000 people, and is equivalent to a total of around 50,000 people. This estimate 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 based on data from the European Union (EU 27), Norway, Iceland and Liechtenstein. This represents a population of 502,282,000 (Eurostat 2008).

Treatment for hairy cell leukaemia 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. Treatment is usually started when symptoms become troublesome: some people with hairy cell leukaemia never need treatment if they do not have any symptoms and the disease is progressing slowly. Currently, the main treatment is chemotherapy (using medicines to kill cancer cells). At the time of submission of the application for orphan drug designation, several medicines were authorised for the disease in the EU.

The sponsor has provided sufficient information to show that murine anti-CD22 antibody variable region fused to truncated Pseudomonas exotoxin 38 might be of potential significant benefit for the treatment of hairy cell leukaemia, because it might act in a different way to other medicines. This assumption will have to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Murine anti-CD22 antibody variable region fused to truncated Pseudomonas exotoxin 38 is made up of an antibody attached to part of a toxin from the bacterium Pseudomonas. Antibodies are proteins that are able to recognise and attach to structures called antigens. The part of the antibody in this medicine recognises and attaches to an antigen called CD22 cell-surface receptor, which is found on the surface of cancerous cells in hairy cell leukaemia. After attaching itself to CD22, the antibody and the attached toxin are taken up into the cells, where the toxin is activated. The toxin then stops the cancerous cells from making new proteins, eventually killing them.

The effects of murine anti-CD22 antibody variable region fused to truncated Pseudomonas exotoxin 38 have been evaluated in experimental models.
At the time of submission of the application for orphan designation, clinical trials in patients with hairy cell leukaemia were ongoing.

At the time of submission, murine anti-CD22 antibody variable region fused to truncated Pseudomonas exotoxin 38 was not authorised anywhere worldwide for hairy cell leukaemia 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 8 October 2008 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 five in 10,000 people in the Community) or the 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.