EU/3/13/1187

Splenic marginal-zone lymphoma is a cancer of a type of white blood cell called B lymphocytes or B cells. In splenic marginal-zone lymphoma, the B cells multiply too quickly and live for too long, so there are too many of them. The abnormal B cells affect the spleen, causing it to become enlarged, and the bone marrow (the spongy tissue inside the large bones in the body, where blood cells are produced).

Splenic marginal-zone lymphoma is a life-threatening disease and long-term debilitating due to damage to the spleen and bone marrow and the risk of the disease transforming into a more aggressive form of lymphoma.

At the time of designation, splenic marginal-zone lymphoma affected approximately 0.05 in 10,000 people in the European Union (EU). This was equivalent to a total of around 2,500 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 509,000,000 (Eurostat 2013).

At the time of designation, the main treatments for splenic marginal-zone lymphoma used in the EU included immunotherapy (using the body's own immune system to kill cancer cells) with the medicine rituximab, chemotherapy (anticancer medicines), and radiotherapy (treatment with radiation).

The sponsor has provided sufficient information to show that idelalisib might be of significant benefit for patients with splenic marginal-zone lymphoma because early studies show that it might improve the outcome of patients with marginal-zone lymphoma whose disease was resistant to or had come back after existing treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Idelalisib blocks the effects of an enzyme called PI3K-delta which is a member of a family of enzymes called phosphoinositide-3-kinases (PI3K) that plays an important role in the growth, migration and survival of white blood cells. PI3K-delta is active in the abnormal B cells of patients with splenic marginal-zone lymphoma, stimulating their growth and survival. By blocking its effects, the medicine is expected to reduce the growth and survival of the abnormal B cells.

The effects of idelalisib have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with idelalisib in patients with splenic marginal-zone lymphoma were ongoing.

At the time of submission, idelalisib was not authorised anywhere in the EU for splenic marginal-zone lymphoma. Orphan designation of idelalisib had been granted in the EU for lymphoplasmacytic lymphoma and follicular lymphoma, and in the United States for chronic lymphocytic leukaemia.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 11 July 2013 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.