EU/3/16/1757: Orphan designation for the treatment of myelofibrosis

Myelofibrosis is a disease in which fibrous tissue forms in the bone marrow (the spongy tissue inside the large bones where blood cells are produced), interfering with normal blood cell production. This causes some immature blood cells to migrate from the bone marrow to other organs, such as the spleen and liver, which become enlarged. Symptoms of the disease include bone pain, tiredness, weakness, weight loss, fever and bleeding.

Myelofibrosis is a debilitating disease that is long-lasting and life-threatening because it can lead to severe anaemia (low red blood cell counts) and infections, and can result in leukaemia (cancer of the white blood cells).

At the time of designation, myelofibrosis affected less than 1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 51,000 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 513,700,000 (Eurostat 2016).

At the time of designation, busulfan, hydroxycarbamide and ruxolitinib were authorised in the EU for myelofibrosis. In addition, medicines were authorised to treat the symptoms, including erythropoietin (a hormone that stimulates the production of red blood cells) to treat anaemia, and surgery was used to remove the enlarged spleen. In some patients, haematopoietic (blood) stem cell transplantation was used to treat the disease. This is a procedure where the patient's bone marrow is cleared of cells and replaced with stem cells from a donor to form new bone marrow that produces healthy blood cells.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with myelofibrosis because laboratory studies have shown that the medicine may reduce spleen size and stop fibrous tissue forming in the bone marrow. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine blocks the activity of an enzyme called 'lysine-specific demethylase 1' (LSD1). LSD1 is present in high quantities in myelofibrosis patients, leading to the production of abnormal immature blood cells. Blocking its activity is expected to allow the production of normal blood cells and cause death of abnormal cells.

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

At the time of submission of the application for orphan designation, no clinical trials with the medicine in patients with myelofibrosis had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for myelofibrosis 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 8 September 2016 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.