EU/3/10/810: Orphan designation for the treatment of post-essential thrombocythaemia myelofibrosis

Myelofibrosis is a disease in which the bone marrow (the spongy tissue inside the large bones) becomes dense and fibrous, and starts producing abnormal immature blood cells that replace the normal blood cells. It can develop as a reaction to essential thrombocythaemia (overproduction of platelets, components that help the blood to clot). 'Essential' means that the thrombocythaemia is not caused by any known condition.

In myelofibrosis, some immature blood cells migrate from the bone marrow to other organs, such as the spleen and liver, where they mature. This causes the organs to become enlarged. Patients with myelofibrosis can develop several symptoms, including pain in the bones, fever, tiredness, weakness, weight loss, infections and bleeding.

Post-essential thrombocythaemia myelofibrosis is a debilitating disease that is long-lasting and may be 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, post-essential thrombocythaemia myelofibrosis affected less than 0.15 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 7,600 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. At the time of designation, this represented a population of 506,300,000 (Eurostat 2010).

At the time of designation, although hydroxyurea and busulfan were authorised in the EU for primary myelofibrosis (myelofibrosis of unknown cause), there were no treatments authorised specifically for post-essential thrombocythaemia myelofibrosis.

Treatments for this disease were aimed at relieving symptoms. They included androgens (male hormones), glucocorticoids (a type of steroid) and erythropoietin (a hormone that stimulates the production of red blood cells) to treat anaemia, and surgery or radiation to remove or shrink the enlarged spleen. In some patients, allogeneic stem-cell transplantation was used. This is a complex procedure where the patient receives stem cells from a matched donor to help restore the bone marrow.

This medicine is thought to work by blocking an enzyme known as Janus kinase 2 (JAK2), which can be found in some receptors on the surface of cells and is involved in the production and growth of blood cells. In myelofibrosis, JAK2 is overactivated. By blocking this enzyme, the medicine is expected to slow down the abnormal growth of blood cells, reducing the symptoms of the disease.

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

At the time of submission of the application for orphan designation, clinical trials with the medicine including patients with post-essential thrombocythaemia myelofibrosis were ongoing.

At the time of submission, this medicine was not authorised anywhere in the EU for post-essential thrombocythaemia myelofibrosis. Orphan designation of the medicine had been granted in the United States for the treatment of secondary and primary myelofibrosis.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 9 September 2010 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.