EU/3/05/328

Peripheral T-cell lymphoma belongs to the group of non-Hodgkin's lymphoma, which is a type of cancer that originates from the lymphatic system. The lymphatic system is part of the body's immune system and helps fighting 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), which are connected by a network of tiny lymphatic vessels. There are two main types of cells, which make up the lymphatic tissue. These cells are called lymphocytes and belong to the group of white blood cells. The two types are called B lymphocytes (B cells) and T lymphocytes (T cells). Most lymphocytes start growing in the bone marrow. The T cells go from the bone marrow to the thymus where they continue to mature. Normally, the lymphatic cells grow in a controlled manner. Peripheral T-cell lymphoma is caused by the uncontrolled growth of T-lymphocytes originating from the thymus in different stages of maturity. Different types of peripheral T-cell lymphoma 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. 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 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 25), Norway, Iceland and Liechtenstein. This represents a population of 459,700,000 (Eurostat 2004).

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 responses 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 regimens of several chemotherapeutic agents are given.

Depsipeptide might be of potential significant benefit for the treatment of peripheral T-cell lymphoma because it is expected to act in a different way than 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.

Enzymes are proteins produced by the cells of the body that speed up the conversion of certain substances into other substances. Depsipeptide appears to inhibit or reduce the activity of an enzyme, called histone deacetylase, which is necessary for cell growth and multiplication. As these enzymes are no more available to help the formation of new genetic material, this might lead to the arrest of cell growth. Since peripheral T-cell lymphoma is caused by the uncontrolled growth of the T-lymphocytes, depsipeptide might help in slowing down or stopping this uncontrolled cell growth.

The effects of depsipeptide 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 were ongoing.

Depsipeptide was not authorised anywhere worldwide for the treatment of peripheral T-cell lymphoma, at the time of submission. Orphan designation of depsipeptide was granted in Europe and in the United States for the treatment of cutaneous T-cell lymphoma.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 9 September 2005 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 Community) 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.