EU/3/15/1567: Orphan designation for the treatment of blastic plasmacytoid dendritic cell neoplasm

Blastic plasmacytoid dendritic cell neoplasm is an aggressive type of blood cancer in which the bone marrow (the spongy tissue inside the large bones, where blood cells are produced) produces large numbers of immature white blood cells called 'plasmacytoid dendritic cells'. These may build up in the bone marrow and take the place of normal blood cells. Most patients develop non-itchy damaged areas in the skin, which often look like bruises or nodules. The disease may also cause enlargement of the spleen or liver and a reduction of the number of circulating blood cells.

Blastic plasmacytoid dendritic cell neoplasm is a life-threatening disease that is associated with poor overall survival.

At the time of designation, blastic plasmacytoid dendritic cell neoplasm affected approximately 1.2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 62,000 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, no satisfactory methods were authorised in the EU for the treatment of blastic plasmacytoid dendritic cell neoplasm. Patients often received radiotherapy and medicines authorised for other types of blood cancers. Some patients were also given stem cell transplantation, a complex procedure where the patient receives stem cells from a matched donor to help restore the bone marrow.

This medicine contains a toxin (a substance which is poisonous for cells) called diphtheria toxin, which has been 'fused' to a protein called 'interleukin-3'. Although is it not fully clear how the medicine works, it is expected that the interleukin-3 will attach to interleukin-3 receptors, which are found at high levels on the surface of some cancer cells. Once attached to cancer cells, the medicine is expected to be taken up by the cells. The toxin would then be released inside cancer cells, thus killing them.

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 blastic plasmacytoid dendritic cell neoplasm were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for blastic plasmacytoid dendritic cell neoplasm. Orphan designation of the medicine 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 8 October 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.