EU/3/04/205: Orphan designation for the treatment of cutaneous T-cell lymphoma

Cutaneous T-cell lymphoma is a type of cancer of the lymphatic system localised in the skin. It belongs to a group of lymphomas called non-Hodgkin's lymphomas (there are more than 20 different types of non-Hodgkin's lymphoma). The lymphatic system is part of the body's immune system and helps 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), 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 and mature there. Cutaneous T-cell lymphoma is a cancer of the T lymphocytes and most often occurs in people aged between 40 and 60. Unlike other forms of non-Hodgkin's lymphomas, cutaneous T-cell lymphoma mainly affects the skin. It is caused by the uncontrolled growth of T-cells within the skin. Cutaneous T-cell lymphoma is a serious and life-threatening condition.

Treatments for cutaneous T-cell lymphoma can be local (limited to the part of the body concerned by the disease) and systemic (distributed throughout the patients body). Local treatments include medicines applied to the skin, therapies using light of a particular wavelength (ultraviolet light) and X-rays. Systemic treatments include medicines such as glucocorticosteroids (a group of medicines derived from cortisone, also used as agents against itching), cytotoxic agents (medicines that kill cells), immunotherapy (using drugs that stimulate the body's own immune system to kill the cancer cells) and photopheresis (white blood cells are modified by exposure to ultraviolet light). Several products were authorised for the treatment of cutaneous T-cell lymphoma within the Community at the time of submission of the application for orphan drug designation. Suberoylanilide hydroxamic acid (SAHA) might be of potential significant benefit for the treatment of cutaneous T-cell lymphoma. This assumption remains to be proven. This will be necessary to maintain the orphan status.

At the time of designation, cutaneous T-cell lymphoma affected approximately 1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 46,000 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 (EU 25), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 464,200,000 (Eurostat 2004).

Enzymes are proteins produced by the human body that speed up the conversion of certain substances into other substances. SAHA appears to block 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 cutaneous T-cell lymphoma is caused by the uncontrolled growth of the T cells, SAHA might help in slowing down or stopping this uncontrolled cell growth.

At the time of submission of the application for orphan designation, clinical trials in patients with cutaneous T-cell lymphoma were ongoing.

Suberoylanilide hydroxamic acid (SAHA) was not marketed anywhere worldwide for cutaneous T-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 14 May 2004 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.