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Orphan designation

On 5 August 2011, orphan designation (EU/3/11/886) was granted by the European Commission to Cres Pharmaceuticals Limited, United Kingdom, for N-(cyanomethyl)-4-(2-{[4-(morpholin-4-yl)phenyl]amino}pyrimidin-4-yl)benzamide, dihydrochloride salt for the treatment of post-polycythaemia vera myelofibrosis.

The sponsorship was transferred to YM BioSciences (UK) Limited, United Kingdom, in February 2012 and subsequently to Gilead Sciences International Ltd, United Kingdom, in May 2013.

For a list of the administrative updates to this public summary of opinion, please refer to the PDF document below.

What is post-polycythaemia vera myelofibrosis?

Myelofibrosis is a disease in which the bone marrow (the spongy tissue inside the large bones where blood cells are produced) becomes dense and fibrous, and starts producing abnormal immature blood cells that replace the normal blood cells. It can develop following polycythaemia vera (overproduction of red blood cells), in which case the disease is known as post-polycythaemia vera myelofibrosis.

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 the disease can develop several symptoms, including bone pain, fever, tiredness, weakness, weight loss, infections and bleeding.

Post-polycythaemia vera 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).

What is the estimated number of patients affected by the condition?

At the time of designation, post-polycythaemia vera myelofibrosis affected less than 0.15 in 10,000 people in the European Union (EU)*. This is equivalent to a total of fewer than 8,000 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 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 507,700,000 (Eurostat 2011).

What treatments are available?

At the time of designation, although hydroxycarbamide and busulfan were authorised in the EU for primary myelofibrosis (myelofibrosis of unknown cause), there were no treatments authorised specifically for post-polycythaemia vera myelofibrosis. Medicines were authorised to treat the symptoms, including 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 to treat the disease. This is a complex procedure where the patient receives stem cells from a matched donor to help restore the bone marrow.

How is this medicine expected to work?

This medicine is thought to work by blocking some enzymes known as Janus kinases (JAKs). These enzymes can be found in some receptors on the surface of cells and are involved in the reproduction and growth of blood cells. In myelofibrosis, JAKs are more active than normal. By blocking these enzymes, this medicine is expected to slow down the abnormal growth of blood cells, reducing the symptoms of the disease.

What is the stage of development of this medicine?

The effects of N-(cyanomethyl)-4-(2-{[4-(morpholin-4-yl)phenyl]amino}pyrimidin-4-yl)benzamide, dihydrochloride salt 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 myelofibrosis were ongoing.

At the time of submission, this medicine was not authorised anywhere in the EU for post-polycythaemia vera myelofibrosis. Orphan designation of the medicine had been granted in the United States for myelofibrosis.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 5 May 2011 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:
  • 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.

Key facts

Product details for <p>N-(cyanomethyl)-4-(2-{[4-(morpholin-4-yl)phenyl]amino}pyrimidin-4-yl)benzamide, dihydrochloride salt</p>
Active substanceN-(cyanomethyl)-4-(2-{[4-(morpholin-4-yl)phenyl]amino}pyrimidin-4-yl)benzamide, dihydrochloride salt
Medicine Name
Disease/conditionTreatment of post-polycythaemia vera myelofibrosis
Date of decision05/08/2011
Orphan decision numberEU/3/11/886

Review of designation

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.

Sponsor’s contact details:

Gilead Sciences International Ltd.
Flowers Building
Granta Park
CB21 6GT
United Kingdom
Tel. +44 (0)1223 897300
Fax + 44 (0)1223 897284

Patients' organisations:

For contact details of patients’ organisations whose activities are targeted at rare diseases, see:

  • Orphanet, a database containing information on rare diseases which includes a directory of patients’ organisations registered in Europe;
  • European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.