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Orphan designation

On 29 November 2007, orphan designation (EU/3/07/506) was granted by the European Commission to Prof Etienne Sokal, Belgium, for heterologous human adult liver-derived stem cells for the treatment of Crigler-Najjar syndrome.

The sponsorship was transferred to Promethera Biosciences, Belgium, in June 2010.

What is Crigler-Najjar syndrome?

Crigler-Najjar syndrome is an inherited disorder that results in failure of proper bilirubin elimination from the liver via the bile. Bilirubin is a product that results from the breakdown of haemoglobin from old or damaged red blood cells. When bilirubin cannot be released from the liver, it accumulates in the body and becomes toxic for the brain. It is associated with jaundice (yellowish colour of the skin and the eyes). The condition is chronically debilitating and life-threatening.

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

At the time of designation, Crigler-Najjar syndrome affected affect less than 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 5,000 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 500,300,000 (Eurostat 2007).

What treatments are available?

Phototherapy, which breaks down bilirubin, is used in these patients. However, the only curative treatment is liver transplantation. Liver transplantation refers to a procedure in which a failed liver is removed from the patient's body and liver tissue from a healthy donor is transplanted into the same location. The procedure is the most common method used to transplant livers. However, liver transplantation is a complex operation, with important surgical risks, and is often associated with significant postoperative mortality. At the time of submission of the application for orphan drug designation, other methods of treatment for Crigler-Najjar syndrome were authorised in the Community.

Heterologous human adult liver derived stem cells might be of potential significant benefit for the treatment of Crigler-Najjar syndrome because they might improve the long-term outcome of the patients. The assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

How is this medicine expected to work?

Liver cells are specialised to perform certain specific functions. Heterologous human adult liver-derived stem cells are stem cells isolated from an adult liver with the capacity to differentiate (to change their characteristics and capacities and acquire new specific functions) into more mature liver cells. The cells will come from a donor and not the patient (heterologous). It is planned to isolate and treat the cells in such a way that they might be given to patients suffering from Crigler-Najjar syndrome. The mechanism of action is not fully understood but it is believed that the heterologous human adult liver derived stem cells will become mature and functional liver cells, giving support to the liver function.

What is the stage of development of this medicine?

At the time of submission of the application for orphan designation, the effects of heterologous human adult liver derived stem cells had been evaluated in experimental models.

Heterologous human adult liver-derived stem cells were not authorised anywhere in the world for the treatment of Crigler-Najjar syndrome, or designated as an orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 10 October 2007 recommending the granting of this designation.

Opinions on orphan medicinal products designations are based on the following cumulative criteria:
  • the seriousness of the condition, 
  • the existence of alternative methods of diagnosis, prevention or treatment and 
  • 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

Product details for <p>Heterologous human adult liver-derived stem cells</p>
Active substanceHeterologous human adult liver-derived stem cells
Medicine Name
Disease/conditionTreatment of Crigler-Najjar syndrome
Date of decision29/11/2007
Orphan decision numberEU/3/07/506

Review of designation

Sponsor’s contact details:

Promethera Biosciences
Watson & Crick Hill
11 Rue Granbonpré
1435 Mont-Saint-Guibert
Tel. +32 10 39 43 00
Fax +32 10 39 43 01

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.