EU/3/11/850: Orphan designation for the treatment of peripheral T-cell lymphoma (nodal, other extranodal and leukaemic/disseminated)

Peripheral T-cell lymphoma is a cancer of the lymphatic system, a network of vessels that transport fluid from tissues through the lymph nodes and into the bloodstream. In peripheral T-cell lymphoma there is uncontrolled growth of T lymphocytes (T cells), a type of white blood cell found in the lymphatic system, which appear in the blood circulating in peripheral parts of the body. Different types of peripheral T-cell lymphoma have been identified and categorised as nodal, other extranodal and leukaemic/disseminated.

The symptoms of the disease vary according to the type of lymphoma, but the first sign is usually a lump in the neck, under the arm or in the groin area, which is caused by an enlarged lymph node. The lymphoma may also affect other organs in the body such as the bone marrow, liver and the skin.

Peripheral T-cell lymphoma is a serious and life-threatening condition because in most cases the disease comes back within one year after initial treatment and is associated with poor overall survival.

At the time of designation, peripheral T-cell lymphoma affected less than 0.7 in 10,000 people in the European Union (EU)*. This is equivalent to a total of fewer than 35,000 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 27), Norway, Iceland and Liechtenstein. This represents a population of 506,300,000 (Eurostat 2011).

At the time of designation, there were no specific treatments for peripheral T-cell lymphoma, but the disease was treated in the same way as the broader class of lymphomas known as non-Hodgkin's lymphomas, for which several medicines were authorised in the EU. The main treatment was chemotherapy (medicines to treat cancer), sometimes in combination with radiotherapy (treatment with radiation).

The sponsor has provided sufficient information to show that darinaparsin might be of significant benefit for patients with peripheral T-cell lymphoma because it works in a different way to available medicines and early studies in experimental models show that it might improve the treatment of patients with this condition. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Darinaparsin is a substance based on arsenic. It is expected to work by damaging and killing cancer cells through various mechanisms. Its main target is the 'mitochondria', a small energy-producing structure within cells. Darinaparsin is expected to stimulate the production of toxic molecules containing oxygen, which might stop the normal functioning of mitochondria in the cancer cells and thereby leading to cell death. Darinaparsin is also thought to interfere with certain enzymes necessary for cell growth and multiplication. Through these actions, darinaparsin is expected to slow down the uncontrolled growth of T cells.

The effects of darinaparsin have been evaluated in experimental models.

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

At the time of submission, darinaparsin was not authorised anywhere in the EU for the treatment of peripheral T-cell lymphoma. Orphan designation of darinaparsin had been granted in the United States of America for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 12 January 2011 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.