EU/3/07/444: Orphan designation for the treatment of peripheral T-cell lymphoma (nodal, other extranodal and leukaemic/disseminated)

Peripheral T-cell lymphoma belongs to the group of non-Hodgkin's lymphomas, which are cancers originating from the lymphatic system. The lymphatic system is part of the body's immune system and helps to fight infections. It is a complex system, made up of organs such as the bone marrow, the thymus (a gland behind the breast bone), the spleen (an organ in the abdomen, near the stomach), and the lymph nodes (or lymph glands, located throughout the body). The main type of cells in the lymphatic tissue are called lymphocytes, and belong to the broader group of white blood cells. There are two main types of lymphocytes: the B lymphocytes (B cells), and the T lymphocytes (T cells). Normally, the lymphatic cells grow in a controlled manner. Peripheral T-cell lymphoma is caused by the uncontrolled growth of T-lymphocytes, in different stages of maturity. Several different types of peripheral T-cell lymphomas have been identified and categorised (nodal, other extranodal and leukaemic/disseminated). Patients most often present with generalised lymph node enlargement, liver enlargement and bone marrow involvement; sometimes fever is present. Peripheral T-cell lymphoma is a serious and life-threatening condition.

At the time of designation, peripheral T-cell lymphoma (nodal, other extranodal and leukaemic/disseminated) affected less than 1 in 10,000 people in the European Union (EU)*. This is equivalent to a total of fewer than 46,000 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 based on data from the European Union (EU 25), Norway, Iceland and Lichtenstein. This represents a population of 459,700,000 (Eurostat 2004). This estimate is based on available information and calculations presented by the sponsor at the time of the application.

There are currently several medicinal products authorised in the Community for treatment of non-Hodgkin lymphoma. The choice of treatment depends in particular on the extension of the disease as well as on the response to therapies previously prescribed. Although chemotherapy (using medicines to kill cancer cells) is the current standard of care for peripheral T-cell lymphoma, most tumours will come back, and then more intensive treatments are given, using several chemotherapeutic agents together.

Pralatrexate might be of potential significant benefit for the treatment of peripheral T-cell lymphoma (nodal, other extranodal and leukaemic/disseminated) because it acts as other drugs used currently for the treatment of the condition but might have a different activity. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

Enzymes are proteins produced by the cells of the body that speed up the conversion of certain substances into other substances. Pralatrexate inhibits (blocks) the activity of an enzyme, called dihydrofolate reductase, which is necessary for cell growth and multiplication. As these enzymes are less available to help many chemical reactions in growing cells, this might lead to the arrest of cell growth. Since peripheral T-cell lymphoma is caused by the uncontrolled growth of the T-lymphocytes, pralatrexate might help in slowing down or stopping this uncontrolled cell growth.

The effects of pralatrexate were evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with peripheral T cell lymphoma (nodal, other extranodal and leukaemic/disseminated) were ongoing.

Pralatrexate was not authorised anywhere in the world for the treatment of peripheral T-cell lymphoma, at the time of submission. Orphan designation of pralatrexate was granted in the United States for the treatment of T-cell lymphoma.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 8 March 2007 recommending the granting of this designation.

• 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.