EU/3/08/548: Orphan designation for the treatment of multiple myeloma

Multiple myeloma is a cancer of a type of white blood cell called plasma cells. Plasma cells are found in the bone marrow, the spongy tissue inside the large bones in the body. In multiple myeloma, the division of plasma cells gets out of control, and results in abnormal, immature plasma cells multiplying and filling up the bone marrow. This interferes with production of the 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 life-threatening disease.

At the time of designation, multiple myeloma affected approximately 1.3 in 10,000 people in the European Union (EU). This was equivalent to a total of around 65,000 people*, and is below the threshold for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and 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. At the time of designation, this represented a population of 502,800,000 (Eurostat 2008).

At the time of submission of the application for orphan-drug designation, several medicines were authorised for multiple myeloma in the European Union. The main treatment for multiple myeloma is chemotherapy (medicines to treat cancer) usually combined with steroids (a group of chemical substances, the so-called hormones, which have an effect on the activity of certain organs). Interferon alfa can also be used in combination with chemotherapy although the way it works in cancer treatment is not fully understood. Radiotherapy (using radiation to kill cancer cells) can be very useful to treat pain and weakened bones.

The sponsor has provided satisfactory documentation to justify the assumption that carfilzomib could be of benefit in the treatment of multiple myeloma because it may offer a new way of killing cancer cells and stopping tumour growth. This assumption will need to be confirmed at the time of a marketing authorisation, to maintain the orphan status of the medicine.

Carfilzomib is a proteasome inhibitor. It blocks the proteasome, a system in cells that breaks down proteins when they are no longer needed. When the proteins in the cancer cells, such as the proteins that control the growth of the cells, are not broken down, the cells are affected and they eventually die. This is expected to reduce the number of multiple myeloma cells.

The effects of cafilzomib have been evaluated in experimental models. At the time of submission of the application for orphan designation, clinical trials in patients with multiple myeloma were ongoing.

At the time of submission, carfilzomib was not authorised anywhere in the world for the treatment of multiple myeloma, or designated as orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 8 April 2008 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 Community) 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.