EU/3/16/1745

Diffuse large B-cell lymphoma is a type of blood cancer and the most common form of a group of blood cancers known as non-Hodgkin lymphomas.

Diffuse large B-cell lymphoma affects a type of white blood cell called B lymphocytes, or B cells. In patients with this cancer, the B cells multiply too quickly and live for too long, so there are too many of them in the lymph nodes. The first sign of the disease is usually a lump in the neck, under the arm or in the groin area, which is caused by an enlarged lymph node. Patients with diffuse large B-cell lymphoma may also have fever, tiredness, night sweats or weight loss that have no obvious cause.

Although some people with diffuse large B-cell lymphoma can be cured, it remains a serious and life-threatening disease, particularly when the disease is diagnosed late or has come back after treatment.

At the time of designation, diffuse large B-cell lymphoma affected less than 4.5 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 231,000 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 28), Norway, Iceland and Liechtenstein. This represents a population of 513,700,000 (Eurostat 2016).

At the time of designation, several medicines were authorised for the treatment of diffuse large B-cell lymphoma in the EU. The main treatment was chemotherapy (medicines to treat cancer) usually in combination with medicines called monoclonal antibodies and sometimes with radiotherapy (treatment with radiation). Autologous haematopoietic (blood) stem-cell transplantation was also used in patients at risk of the disease coming back after treatment. This is a procedure where the patient's bone marrow is replaced with the patient's own stem cells to form new bone marrow that produces healthy blood cells.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with diffuse large B-cell lymphoma because an early clinical study showed that it may be effective in patients whose disease had come back after previous treatment. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

The B cells in patients with diffuse large B-cell lymphoma produce a protein on their surface called CD19. To make this medicine, T cells (a different type of white blood cells that are part of the body's natural defences) are taken from the patient. They are then modified in the laboratory by a virus that carries a gene into the cells which allows them to target CD19. The modified T cells are grown to increase their numbers before being given back to the patient. Once the modified T cells are returned to the patient, they are expected to recognise CD19 on the cancerous B cells, allowing the T cells to target and kill them.

The virus used in this medicine ('lentivirus') is modified in order not to cause disease in humans.

The effects of the medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with diffuse large B-cell lymphoma were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for diffuse large B-cell lymphoma. Orphan designation of the medicine had been granted in EU for the treatment of B lymphoblastic leukaemia/lymphoma and in the United States for the treatment of acute lymphoblastic leukaemia, of chronic lymphocytic leukaemia and of diffuse large B-cell lymphoma.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 8 September 2016 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.