EU/3/08/572 - orphan designation for treatment of chronic idiopathic myelofibrosis

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

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Please note that this product was withdrawn from the Community Register of designated orphan medicinal products in February 2015 on request of the sponsor.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 7 November 2008, orphan designation (EU/3/08/572) 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 chronic idiopathic myelofibrosis.

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 chronic idiopathic myelofibrosis has been authorised in the EU as Jakavi since 23 August 2012.

What is chronic idiopathic myelofibrosis?

Chronic idiopathic myelofibrosis is a disease in which cancer cells are found in the blood and in the bone marrow. The bone marrow is the spongy tissue inside the large bones in the body. Normally the bone marrow makes cells called 'blasts' that mature into several different types of blood cell that have specific functions in the body. These include red cells, white cells and platelets. Red blood cells carry oxygen and other materials to all tissues of the body. White blood cells fight infection. Platelets make the blood clot. When myelofibrosis develops, the bone marrow produces large number of abnormal blood cells. In chronic idiopathic myelofibrosis, the abnormal population of cells produces substances that alter the growth media of bone marrow and makes bone marrow very dense and rigid. As the abnormal bone-marrow environment is no more adequate for the cells, some migrate to other sites where proliferation and maturation take place.

Chronic idiopathic myelofibrosis is life-threatening, in particular due to the decreased life expectancy of patients.

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

At the time of designation, chronic idiopathic myelofibrosis affected less than 0.5 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 25,000 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).

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*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).

What treatments are available?

At the time of submission, hydroxyurea was authorised in the Community for the treatment of the condition. Other drugs were used for the treatment of symptoms of the disease such as androgen, glucocorticoids or erythropoietin for anaemia. Splenectomy (surgical removal of the spleen) was performed in case of excessive enlargement of the spleen (splenomegaly), and bone-marrow transplantation in some patients.

How is this medicine expected to work?

Protein kinases are enzymes that regulate many functions in the cell. In chronic idiopathic myelofibrosis, a chain of these molecules are involved in the development of the disease. This is known as the Janus-kinase (JAK) pathway. The product is an inhibitor of the JAK pathway and, by doing this, it is expected to inhibit the development of the disease and reverse some of the negative consequences derived form the condition.

What is the stage of development of this medicine?

The effects of (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphate have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with chronic idiopathic myelofibrosis were ongoing.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 10 September 2008 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 since 23 August 2012 for 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.

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 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.

EU/3/08/572: Public summary of positive opinion for orphan designation of (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphate for the treatment of chronic idiopathic myelofib...

AdoptedReference Number: EMEA/COMP/488810/2008 Rev. 5

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 chronic idiopathic myelofibrosis
• Orphan designation status:
  Withdrawn
• EU designation number:
  EU/3/08/572
• Date of designation:
  07/11/2008
• 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.

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¹ At 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.
² The 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.