EU/3/14/1244: Orphan designation for the treatment of polycythaemia vera

Polycythaemia vera is a disease in which the bone marrow (the spongy tissue inside the large bones where blood cells are produced) produces too many red blood cells. This makes the blood thicker and can result in reduced blood flow to the organs and occasionally the formation of blood clots. While some patients with polycythaemia vera do not have any symptoms, others may have itching, tiredness, headache, blurred vision and an enlarged liver and spleen. Patients who develop blood clots in the small blood vessels can also experience a wide range of symptoms including burning pains in the hands. Patients with blood clots in the arteries can have strokes.

Polycythaemia vera is a long-term debilitating and life-threatening condition because it may lead to the formation of blood clots and bleeding, and can result in leukaemia (cancer of the white blood cells) and myelofibrosis (a disease of the bone marrow).

At the time of designation, polycythaemia vera affected less than 5 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 256,000 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 28), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 512,900,000 (Eurostat 2014).

At the time of designation, hydroxycarbamide, pipobroman and busulfan were authorised in some Member States to reduce the number of red blood cells in patients with polycythaemia vera. In addition, phlebotomy (removal of some of the blood from the body) and long-term treatment with low-dose aspirin were recommended in some patients to reduce the risk of blood clot formation.

The sponsor has provided sufficient information to show that ruxolitinib might be of significant benefit for patients with polycythaemia vera because early studies indicate that it might improve the outcome of patients whose disease does not respond to hydroxycarbamide. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Ruxolitinib is a medicine that is already authorised under the name of Jakavi for the treatment of myelofibrosis. It works by blocking a group of enzymes known as Janus kinases (JAKs), which are involved in the production and growth of blood cells. In polycythaemia vera, these enzyme are overactive, leading to the production of too many red blood cells. By blocking these enzymes, ruxolitinib is expected to decrease the abnormal production of red blood cells, relieving the symptoms of polycythaemia vera.

The effects of ruxolitinib have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with ruxolitinib in patients with polycythaemia vera were ongoing.

At the time of submission, ruxolitinib was authorised in the EU for the treatment of myelofibrosis.

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

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 9 January 2014 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.