EU/3/10/732: Orphan designation for the treatment of Hodgkin's lymphoma

Hodgkin's lymphoma is a type of cancer of the lymphatic system, a network of vessels that transport fluid from tissues through the lymph nodes and into the bloodstream. Because lymph nodes are found throughout the body, the cancer can begin in almost any part of the body. In Hodgkin's lymphoma, white blood cells in the lymphatic system multiply too quickly and live for too long. These cancer cells can spread through the lymphatic system to other lymph nodes or through the bloodstream to other organs such as the spleen, where they can form new tumours.

Many people with Hodgkin's lymphoma can be cured if the disease is found and treated early. However, despite the treatments available, Hodgkin's lymphoma remains a serious and life-threatening disease, mainly because it leads to poor survival in patients whose disease does not respond to treatment or has come back after previous treatment.

At the time of designation, Hodgkin's lymphoma affected between 1 and 4 in 10,000 people in the European Union (EU). This was equivalent to a total of between 51,000 and 203,000 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 506,300,000 (Eurostat 2010).

At the time of designation, several medicines were authorised for the treatment of Hodgkin's lymphoma in the EU. The main treatments for Hodgkin's lymphoma included chemotherapy (medicines to treat cancer) and radiotherapy (treatment with radiation). Autologous bone-marrow transplantation was also used when the disease had not responded to treatment or had come back after treatment. This is a complex procedure where the bone marrow of the patient is destroyed and replaced with healthy bone marrow previously obtained from the same patient.

The sponsor has provided sufficient information to show that entinostat might be of significant benefit for patients with Hodgkin's lymphoma because it works in a different way to existing treatments and may represent an alternative treatment option for patients. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Entinostat is expected to work by blocking the activity of proteins called class-I histone deacetylases, which are involved in turning genes 'on' and 'off' within cells. In Hodgkin's lymphoma, entinostat is expected to keep the genes that suppress the division and growth of the tumour cells switched 'on'. This is expected to lead to a reduction in the growth and division of the lymphoma cells.

The effects of entinostat have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with entinostat in patients with Hodgkin's lymphoma were ongoing.

At the time of submission, entinostat was not authorised anywhere in the EU for Hodgkin's lymphoma or designated as an 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 3 February 2010 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.