EU/3/10/740: 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 becomes out of control, 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 that is associated with poor long-term survival.

At the time of designation, multiple myeloma affected less than 2.2 in 10,000 people in the European Union (EU)*. This is equivalent to a total of fewer than 111,000 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 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 27), Norway, Iceland and Liechtenstein. This represents a population of 506,500,000 (Eurostat 2010).

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 steroids to reduce the activity of the immune system, the body's natural defences. Radiotherapy (treatment with radiation) was considered to be very useful in treating pain and weakened bones.

Interferon alfa, a protein normally produced by the body during viral infections, was sometimes used in combination with chemotherapy.

The sponsor has provided sufficient information to show that perifosine might be of significant benefit for patients with multiple myeloma because it works in a different way to existing treatments, and early studies show that it might be used in patients who do not respond to existing treatments. In addition, perifosine will be available as tablets, whereas most of the existing treatments need to be given by injection. These assumptions will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Perifosine is expected to work by blocking some enzymes, known as protein kinases B (or Akt). These enzymes are involved in stimulating cells to grow and divide. Cancerous cells grow and divide uncontrollably. By blocking these enzymes, the medicine is expected to help control the growth and division of the cancerous cells and slow down the development of multiple myeloma.

The effects of perifosine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with perifosine in patients with multiple myeloma were ongoing.

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

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 3 February 2010 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.