EU/3/03/175

Mantle-cell lymphoma belongs to the group of non-Hodgkin's lymphoma. Lymphoma is a type of cancer that originates from the lymphatic system. The lymphatic system is part of the immune system, the body's natural defence against infection and disease. It is a complex system made up of organs such as bone marrow (the spongy tissue inside the large bones in the body), the thymus and the spleen, and a network of lymph nodes throughout the body that are connected by lymphatic vessels.

Normally, the lymphatic cells grow in a controlled manner. However, in lymphoma a lymphatic cell clone continues to grow and divides in an uncontrolled manner, developing into a tumour. Lymphoma cells generally grow in lymph nodes. There are several different types of lymphoma depending on the type of lymphatic cancer cells. In mantle-cell lymphoma, the cancer cells are related to the blood cells called B lymphocytes. This disease affects mainly adult males of over 50 years. Mantle-cell lymphoma is a serious and life-threatening condition.

At the time of designation, mantle-cell lymphoma affected approximately 0.4 in 10,000 people in the European Union (EU). This was equivalent to a total of 15,000 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 of mantle-cell lymphoma includes chemotherapy (using drugs to kill cancer cells), radiotherapy (using high-dose X-rays or other high-energy rays to kill cancer cells) and immunotherapy (using drugs that stimulate the body's own immune system to kill the cancer cells).

There are currently several medicinal products authorised in the Community for treatment of non-Hodgkin lymphomas. The choice of treatment depends in particular on the extension of the disease as well as on the responses to therapies previously prescribed. Recombinant antibody derivative against human CD19 and CD3 could be of potential significant benefit for the treatment of mantle-cell lymphoma. The potential benefit is mainly because it may act in a different way to other drugs. 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 and link 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 to lymphoma cells (that display a protein called CD19 on the surface) as well as to cells of the immune system called T lymphocytes (that display CD3). By binding both these cells, it is thought that the antibody may help the body's immune system to recognise 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, phase-I clinical trials including patients with mantle-cell lymphoma were ongoing.

Recombinant antibody derivative against human CD19 and CD3 was not marketed anywhere worldwide for mantle-cell lymphoma 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 October 2003 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 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.