EU/3/15/1463: Orphan designation for the treatment of plasma cell myeloma

Plasma cell myeloma (also called multiple myeloma) is a cancer of a type of white blood cell called plasma cells. Plasma cells originate in the bone marrow, the spongy tissue inside the large bones of the body. In plasma cell myeloma the division of plasma cells becomes out of control, resulting in abnormal, immature plasma cells multiplying and filling up the bone marrow. These immature cells interfere with the 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.

Plasma cell 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, plasma cell myeloma affected approximately 3.6 in 10,000 people in the European Union (EU). This was equivalent to a total of around 185,000 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 512,900,000 (Eurostat 2015).

At the time of designation, several medicines were authorised for plasma cell myeloma in the EU. The main treatment for plasma cell myeloma was chemotherapy (medicines to treat cancer) usually combined with corticosteroids to reduce the activity of the immune system, the body's natural defences. Where chemotherapy did not work, some patients received an allogeneic stem-cell transplant (a complex procedure where the patient receives stem cells from a matched donor to help restore the bone marrow). Radiotherapy (using radiation to kill cancer cells) was used to treat pain due to bone damage and prevent further damage. Interferon alfa was sometimes used in combination with chemotherapy.

The sponsor has provided sufficient information to show that melphalan flufenamide might be of significant benefit to patients with plasma cell myeloma because early studies showed a response to treatment in patients whose disease had come back or was not responding to previous treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Melphalan flufenamide is a type of chemotherapy medicine known as an alkylating agent. It works by adding a small chemical group called alkyl group to the DNA in cells, altering the DNA and interfering with its function in cell division and growth. As a result, the cells cannot divide and grow and they ultimately die. The medicine acts mainly against fast growing cells, such as cancer cells.

Melphalan flufenamide consists of melphalan (a cancer medicine already authorised to treat plasma cell myeloma) attached to another molecule, flufenamide, which enables it to enter cells more easily. Once inside, free melphalan is released by certain enzymes that are present in higher levels in cancer cells, enabling it to act on their DNA and kill the cell.

The effects of melphalan flufenamide have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with melphalan flufenamide in patients with plasma cell myeloma were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for plasma cell myeloma or designated as an 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 12 February 2015 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.