EU/3/19/2220: Orphan designation for the treatment of mantle cell lymphoma

Mantle cell lymphoma is an aggressive cancer of a type of white blood cell called B lymphocytes, or B cells. In mantle cell lymphoma, the B cells multiply quickly and live for too long, so they build up in the lymph nodes. The first sign of the disease is usually a lump in the neck, under the arm or in the groin, caused by an enlarged lymph node. Patients may also have fever, weight loss, tiredness and night sweats. Mantle cell lymphoma is usually diagnosed in people aged over 50 years. It is more common in men than in women.

Mantle cell lymphoma is a long-term debilitating and life-threatening disease associated with poor survival.

At the time of designation, mantle cell lymphoma affected approximately 0.6 in 10,000 people in the European Union (EU). This was equivalent to a total of around 31,000 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 518,400,000 (Eurostat 2019).

At the time of designation, the main treatments for mantle cell lymphoma included chemotherapy (medicines to treat cancer), immunotherapy (medicines that act on the body's immune system) and radiotherapy (treatment with radiation). Bortezomib, ibrutinib, lenalidomide and temsirolimus were specifically authorised in the EU for the treatment of mantle cell lymphoma that has come back after previous treatment or other treatments have not worked. Haematopoietic (blood) stem-cell transplantation was also used. This is a procedure where cells in the patient's bone marrow are replaced by stem cells to form new bone marrow that produces healthy blood cells.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with mantle cell lymphoma. Early studies showed improved survival in patients whose disease had come back after several treatments with other medicines. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine contains the patient’s own T cells (a type of white blood cell) that have been modified genetically in the laboratory so that they make a protein called chimeric antigen receptor (CAR). CAR can attach to another protein on the surface of cancer cells called CD19.

When the medicine is given to the patient, the modified T cells are expected to attach to CD19 on the cancer cells and kill them, and to activate other T cells to attack the cancer.

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

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

At the time of submission, the medicine was not authorised anywhere in the EU for the treatment of mantle cell lymphoma. Orphan designation had been granted in the United States for the condition.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 10 October 2019, 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.