EU/3/07/442

Diffuse large B-cell lymphoma (DLBCL) is the most common cancer of the lymphatic system. 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 bone marrow, thymus (a gland behind the breast bone), 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. In addition, there are isolated lymphatic cells in most tissues of the body, including the skin. The main cells of the lymphatic system are the lymphocytes that belong to the group of white blood cells. There are two main types of lymphocytes: B-lymphocytes (B cells) and T-lymphocytes (T cells). DLBCL is characterised by uncontrolled growth of the B-lymphocytes and mainly affects the lymph nodes. DLBCL is life-threatening.

At the time of submission of the application for orphan drug designation, treatments included medicines such as cytotoxic agents (medicines that kill cells). One monoclonal antibody was authorised for the treatment of DLBCL within the Community at the time of submission of the application for orphan drug designation.
Enzastaurin hydrochloride might be of potential significant benefit for the treatment of DLBCL because it might improve the long-term outcome of the patients. The assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

Based on the information provided by the sponsor and previous knowledge of the Committee, DLBCL was considered to affect less than 2 in 10,000 persons in the European Union, which, at the time of designation, corresponded to about 100,000 persons.

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed based on data from the European Union (EU 27), Norway, Iceland and Lichtenstein. This represents a population of 498,000,000 (Eurostat 2006). This estimate is based on available information and calculations presented by the sponsor at the time of the application.

Cancer cells need to produce a network of new blood vessels in order to grow. Enzastaurin hydrochloride blocks (inhibits) the function of certain proteins such as protein kinases that are involved in cell growth and multiplication and in the progression of some types of cancer, including DLBCL. The theory is that enzastaurin hydrochloride, through its interference with the function of these proteins, will prevent the DLBCL from growing by preventing tumour cell replication and development of new blood vessels.

The evaluation of the effects of enzastaurin hydrochloride in experimental models is ongoing.

At the time of submission of the application for orphan designation, clinical trials in patients with DLBCL were ongoing.

Enzastaurin hydrochloride was not authorised anywhere worldwide for DLBCL or designated as orphan medicinal product elsewhere for this condition, at the time of submission.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 7 February 2007 a positive opinion recommending the grant of the above-mentioned designation.

• the seriousness of the condition,
• the existence or not of alternative methods of diagnosis, prevention or treatment and
• either the rarity of the condition (considered to affect not more than five in ten thousand persons in the Community) or the insufficient return of development investments.

Designated orphan medicinal products are still investigational products which were considered for 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 will be necessary before this product can be granted a marketing authorisation.