EU/3/10/745: 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 not more than 2.2 in 10,000 people in the European Union (EU)*. This is equivalent to a total of not more 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 high-dose dexamethasone. 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 dexamethasone (40 mg tablet) might be of significant benefit for patients with multiple myeloma because this high-dose formulation will allow patients to take only one tablet instead of the multiple tablets they take with the currently available formulations, which contain between 0.5 and 8 mg dexamethasone. In addition, it might offer a wider availability than the existing formulations, which are not available in some EU countries. These two elements are expected to result in a major contribution to patient care. These assumptions will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Dexamethasone belongs to a group of medicines known as corticosteroids, which reduce the activity of the immune system (the body's natural defences) by attaching to receptors in various types of immune cells. In multiple myeloma, high-dose dexamethasone is used together with chemotherapy to make chemotherapy more effective and to reduce certain side effects of cancer treatment, such as nausea (feeling sick) and vomiting.

The sponsor of this application has not conducted any studies in experimental models with dexamethasone (40 mg tablet). However, it provided the results of studies on the effect of high-dose dexamethasone from the published literature to support its application for orphan designation.

At the time of submission of the application for orphan designation, no clinical trials with dexamethasone (40 mg tablet) in patients with multiple myeloma had been started.

At the time of submission, dexamethasone (40 mg tablet) was not authorised anywhere in the EU for multiple 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 3 March 2010 recommending the granting of this designation.

• the seriousness of the condition,
• the existence of alternative methods of diagnosis, prevention or treatment and
• 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.