EU/3/08/596: Orphan designation for the treatment of Hodgkin's lymphoma

Hodgkin's lymphoma is a type of cancer that develops in the lymphatic system. The lymphatic system is part of the body's immune system: the body's natural defense 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), thymus and spleen, and a network of lymph nodes throughout the body that are connected by lymphatic vessels. As lymphatic tissue is found throughout the body, Hodgkin's lymphoma can begin in almost any part of the body and can spread to almost any tissue or organ in the body. Normally, the growth and duplication of lymphatic cells takes place in a controlled manner, however in Hodgkin's lymphoma this process is out of control and the cells continue to divide, developing into a tumour. Hodgkin's lymphoma can occur in both adults and children; however, treatment for adults may be different from treatment for children. Hodgkin's lymphoma can usually be cured, if found and treated early. Despite the available treatments Hodgkin's lymphoma remains a serious and life threatening condition in certain patients.

At the time of designation, Hodgkin lymphoma affected approximately 1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 50,000 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 on the basis of data from the European Union (EU 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 504,800,000 (Eurostat 2009).

Three different types of standard treatment are available and used: chemotherapy (using drugs to kill cancer cells), radiotherapy (using high-energy x-rays or other types of high-energy rays to kill cancer cells) and surgery (removing all possible cancer tissue in an operation). Bone marrow transplantation is also used. Several treatments had been authorized at the time of submission of the application for orphan drug designation.

The monoclonal antibody against CD30 covalently linked to the cytotoxin monomethylauristatin E could be of significant benefit for the treatment of Hodgkin's lymphoma. The main reasons are that it may offer a new way of targeting and killing cancer cells and it might improve the long-term outcome of the patients. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

CD30 is a molecule that Hodgkin lymphoma cells have on their surface (surface marker). One part of the medicinal product is an antibody against CD30 (anti-CD30), therefore is able to recognise and bind to CD30. The antibody is linked to a small molecule called monomethyl auristatin E, which is cytotoxic (kills rapidly dividing cancer cells). The CD30 antibody part of the product acts as a carrier for the cytotoxic substance. The product is thought to bind specifically on CD30 receptor of the lymphoma cells. Once bound on the cell surface, it is taken up by the cells. Once inside the cancer cells, the cytotoxic molecule, monomethyl auristatin E, gets released and stops cell division. The cancer cells are then expected to undergo programmed cell death.

The effects of monoclonal antibody against human CD30 covalently linked to the cytotoxin monomethylauristatin E have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials in patients with Hodgkin's lymphoma had been started.

At the time of submission, the antibody against human CD30 covalently linked to the cytotoxin monomethylauristatin E was not authorised anywhere in the world for Hodgkin lymphoma or designated as orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 8 October 2008 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 five in 10,000 people in the Community) or the 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 the quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.