EU/3/10/768: Orphan designation for the treatment of primary myelofibrosis

Primary myelofibrosis is a disease of unknown cause 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.

In this disease, 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 primary myelofibrosis can develop several symptoms, including pain in the bones, tiredness, weakness, infections and bleeding.

Primary 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, primary myelofibrosis affected approximately 0.3 in 10,000 people in the European Union (EU). This was equivalent to a total of around 15,000 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, hydroxyurea and busulfan (which are also used to treat cancer) were authorised in the EU for primary myelofibrosis. In addition, treatments aimed at relieving the symptoms of the disease were used. These 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 to remove the enlarged spleen. In some patients, haematopoietic (blood) 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.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with primary myelofibrosis because it works in a different way to existing treatments and because early studies show that it might improve the outcome of patients with this condition. These assumptions will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine is thought to work by blocking an enzyme known as Janus kinase 2 (JAK2). This enzyme can be found in some receptors on the surface of cells and is involved in the reproduction and growth of blood cells. In myelofibrosis, JAK2 is overactivated. By blocking this enzyme, this 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 this medicine including patients with primary myelofibrosis were ongoing.

At the time of submission, this medicine was not authorised anywhere in the EU for primary myelofibrosis. Orphan designation of this medicine had been granted in the United States of America for the treatment of myeloproliferative disorders with the JAK2 V617F mutation.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 2 June 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.