EU/3/11/854: 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 2.6 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 132,000 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 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 507,700,000 (Eurostat 2011).

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 used 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 vorinostat might be of significant benefit for patients with multiple myeloma because early studies show that it might improve the treatment of patients with this condition, when used in combination with existing treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Vorinostat blocks the activity of enzymes called histone deacetylases, which are involved in turning genes 'on' and 'off' within cells. In multiple myeloma, vorinostat is expected to switch 'on' the genes that suppress the division and growth of the tumour cells. This is expected to lead to a reduction in the growth and division of the cancer cells.

The effects of vorinostat have been evaluated in experimental models.

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

At the time of submission, vorinostat was authorised in several countries outside the EU for the treatment of cutaneous T-cell lymphoma.

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

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 12 January 2011 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.