EU/3/15/1487: 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 from the bone marrow, the spongy tissue inside the large bones in 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. This interferes 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 already 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 the medicine might be of significant benefit for patients with plasma cell myeloma because early studies in experimental models have shown that it might improve the outcome of patients with this condition, in particular when added to existing treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Most cancer cells, including plasma cell myeloma cells, produce excess heparanase, an enzyme that is involved in the growth and spread of tumours. This medicine is made up of a modified (oxidised) form of heparin, a natural substance that normally prevents blood from clotting. This modified heparin blocks the action of heparanase and so is expected to slow down the progression of the disease.

The effects of the medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicine 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 16 April 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.