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Orphan designation

On 27 September 2011, orphan designation (EU/3/11/904) was granted by the European Commission to Fresenius Medical Care Deutschland GmbH, Germany, for heterologous human adult liver-derived stem cells for the treatment of ornithine transcarbamylase deficiency.

What is ornithine transcarbamylase deficiency?

Ornithine transcarbamylase deficiency is one of the inherited disorders known as ‘urea cycle disorders’, which cause ammonia to accumulate in the blood. Patients with ornithine transcarbamylase deficiency lack ‘ornithine transcarbamylase’, one of the liver enzymes that are needed to get rid of excess nitrogen. In the absence of this enzyme, nitrogen accumulates in the body in the form of ammonia, which can be toxic at high levels, especially to the brain. Symptoms of the disease usually appear in the first few days of life and include lethargy (lack of energy), vomiting, loss of appetite, seizures (fits) and coma.

The disease is usually milder in females than in males, because it is caused by a damaged gene on the X chromosome. As females have two X chromosomes, the normal gene on their other X chromosome usually compensates for the damage. Men have an X and a Y chromosome.

Ornithine transcarbamylase deficiency is a long-term debilitating and life-threatening disease due to the irreversible damage it can cause to the nervous system.

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

At the time of designation, ornithine transcarbamylase deficiency affected less than 0.1 in 10,000 people in the European Union (EU)*. This is equivalent to a total of fewer than 5,000 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. This represents a population of 506,300,000 (Eurostat 2011).

What treatments are available?

At the time of designation, sodium phenylbutyrate was authorised in the EU for the treatment of some urea cycle disorders, including ornithine transcarbamylase deficiency. In addition, patients were advised to control their dietary intake of proteins, which are rich in nitrogen, to reduce the amount of ammonia formed in the body. Liver transplantation had also been used in some patients.

The sponsor has provided sufficient information to show that heterologous human adult liver-derived stem cells might be of significant benefit for patients with ornithine transcarbamylase deficiency because it works in a different way to existing treatments and early studies in experimental models show that it might improve the treatment of patients with this condition by re-establishing a normally functioning urea cycle. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

This medicine is made up of stem cells derived from the liver of an adult donor (‘heterologous’). Stem cells are cells that can develop into different types of cell. When implanted in a patient, it is believed that these heterologous liver-derived stem cells will develop into mature, healthy liver cells that can produce the ornithine transcarbamylase enzyme. The new cells are therefore expected to restore the normal urea cycle and thereby relieve the symptoms of the disease.

What is the stage of development of this medicine?

The effects of heterologous human adult liver-derived stem cells have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with the medicinal product in patients with ornithine transcarbamylase deficiency had been started.

At the time of submission, the medicinal product was not authorised anywhere in the EU for ornithine transcarbamylase deficiency or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 8 July 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>Heterologous human adult liver-derived stem cells</p>
Active substanceHeterologous human adult liver-derived stem cells
Medicine Name
Disease/conditionTreatment of ornithine transcarbamylase deficiency
Date of decision27/09/2011
Orphan decision numberEU/3/11/904

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:

Fresenius Medical Care Deutschland GmbH
Else-Kröner-Straße 1
61352 Bad Homburg v.d. Höhe
Telephone: +49 61 726 092417
Telefax: +49 6172 609 2381

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.