EU/3/20/2252: Orphan designation for the treatment of multiple myeloma

Multiple myeloma (also called plasma cell myeloma) is a cancer of a type of white blood cell called plasma cells. Plasma cells are produced in the bone marrow, the spongy tissue inside the large bones in the body. In multiple myeloma, the division of plasma cells becomes uncontrolled, resulting in abnormal, immature plasma cells multiplying and filling up the bone marrow. This interferes with production of normal white blood cells, red blood cells and platelets (components that help the blood to clot), leading to complications such as anaemia (low red blood cell counts), bone pain and fractures, raised blood calcium levels and kidney disease.

Multiple myeloma is a debilitating and life-threatening disease particularly because it disrupts the normal functioning of the bone marrow, damages the bones and causes kidney failure.

At the time of designation, multiple myeloma affected approximately 4 in 10,000 people in the European Union (EU). This was equivalent to a total of around 208,000 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 519, 200,000 (Eurostat 2020).

At the time of designation, several medicines were authorised for multiple myeloma in the EU. The main treatment for multiple myeloma was chemotherapy (medicines to treat cancer) usually combined with corticosteroids to reduce the activity of the immune system, the body's natural defences. After chemotherapy, patients received a stem-cell transplant if they were considered suitable for it. Stem-cell transplantation is a procedure where the patient's bone marrow is replaced with 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 multiple myeloma. This is because clinical data in patients who had previously received other types of treatment showed that the medicine was effective in many patients and a high number of them had no signs of the disease after treatment (complete response). This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

The medicine is made up of 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). With this receptor on their surface, the modified cells, called CAR-T cells, can attach to a target on the surface of plasma cells called B-cell maturation antigen (BCMA). When the medicine is given to the patient, the modified T cells are expected to attach to and kill the abnormal plasma cells, thereby helping to clear the cancer from the body.

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 multiple myeloma were ongoing.

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

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 22 January 2020, 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.