EU/3/09/620 - orphan designation for treatment of myelofibrosis secondary to polycythaemia vera or essential thrombocythaemia

(R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphate
OrphanHuman

Overview

Please note that this product was withdrawn from the Community Register of designated Orphan Medicinal Products in February 2015 on request of the sponsor.

On 3 April 2009, orphan designation (EU/3/09/620) was granted by the European Commission to Incyte Corporation Ltd, United Kingdom, for (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphate for the treatment of myelofibrosis secondary to polycythaemia vera or essential thrombocythaemia.

The sponsorship was transferred to Novartis Europharm Limited, United Kingdom, in September 2010.

R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphate in treatment of myelofibrosis secondary to polycythaemia vera or essential thrombocythaemia has been authorised in the EU as Jakavi since 23 August 2012.

Myelofibrosis is a disease in which the bone marrow (the spongy tissue inside the large bones in the body) becomes very dense and rigid, and produces abnormal and immature blood cells that replace the normal blood cells. It can develop as a reaction to polycythaemia vera (overproduction of red blood cells) or 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, tiredness, weakness, infections and bleeding.

Myelofibrosis secondary to polycythaemia vera or essential thrombocythaemia 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, myelofibrosis secondary to polycythaemia vera or essential thrombocythaemia affected approximately 0.01 in 10,000 people in the European Union (EU). This was equivalent to a total of around 500 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 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 502,800,000 (Eurostat 2008).

At the time of designation, although hydroxyurea was authorised in the EU for idiopathic myelofibrosis (myelofibrosis of unknown cause), it was not authorised for myelofibrosis secondary to polycythaemia vera or essential thrombocythaemia.

Treatments for this condition were aimed at relieving the symptoms of the disease, and 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, bone-marrow transplantation was used. This is a complex procedure where the bone marrow of the patient is destroyed and replaced with bone marrow from a matched donor.

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 overactivated. By blocking the enzymes, 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 in patients with myelofibrosis secondary to polycythaemia vera or essential thrombocythaemia were ongoing.

At the time of submission, this medicine was not authorised anywhere in the EU for myelofibrosis secondary to polycythaemia vera or essential thrombocythaemia. Orphan designation of this medicine had been granted in the EU for chronic idiopathic myelofibrosis and 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 9 February 2009 recommending the granting of this designation.

Update: (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphate (Jakavi) was authorised in the EU on 23 August 2012 for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis (also known as chronic idiopathic myelofibrosis), post-polycythaemia-vera myelofibrosis or post-essential-thrombocythaemia myelofibrosis.

  • 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 European Union) 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

Active substance
(R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphate
Medicine name
Jakavi
Intended use
Treatment of myelofibrosis secondary to polycythaemia vera or essential thrombocythaemia
Orphan designation status
Withdrawn
EU designation number
EU/3/09/620
Date of designation
Sponsor

Novartis Europharm Limited

Review of designation

Please note that this product was withdrawn from the Community Register of designated Orphan Medicinal Products in February 2015 on request of the sponsor.

During its meeting of 10-11 May 2012, the Committee for Orphan Medicinal Products (COMP) reviewed the designations EU/3/08/572 and EU/3/09/620 for Jakavi (ruxolitinib1) as an orphan medicinal product for the treatment of chronic idiopathic myelofibrosis and myelofibrosis secondary to polycythaemia vera or essential thrombocythaemia. The COMP assessed whether, at the time of marketing authorisation, the medicinal product still met the criteria for orphan designation. The Committee looked at the seriousness and prevalence of the conditions, and the existence of other satisfactory methods of treatment. As other satisfactory methods of treatment for patients with chronic idiopathic myelofibrosis are authorised in the European Union (EU), the COMP also looked at the significant benefit of the product over existing treatments. The COMP recommended that the orphan designation of the medicine be maintained2.


1At time of orphan designation ruxolitinib was known as (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphate.
2The maintenance of the orphan designation at time of marketing authorisation would, except in specific situations, give an orphan medicinal product 10 years of market exclusivity in the EU. This means that in the 10 years after its authorisation similar products with a comparable therapeutic indication cannot be placed on the market.

Documents related to this orphan designation evaluation

EMA list of opinions on orphan medicinal product designation

EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:

Patients' organisations

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

  • European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.

  • Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe.

EU register of orphan medicines

The list of medicines that have received an orphan designation in the EU is available on the European Commission's website:

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