EU/3/13/1165 - orphan designation for treatment of N-acetylglutamate synthetase (NAGS) deficiency
heterologous human adult liver-derived progenitor cells
OrphanHuman
Overview
On 17 July 2013, orphan designation (EU/3/13/1165) was granted by the European Commission to Promethera Biosciences, Belgium, for heterologous human adult liver-derived progenitor cells for the treatment of N-acetylglutamate-synthetase (NAGS) deficiency.
NAGS deficiency is one of the inherited disorders known as 'urea-cycle disorders', which cause ammonia to accumulate in the blood. Patients with this disorder lack NAGS, one of the liver enzymes that are needed to get rid of excess nitrogen. In the absence of this liver enzyme, excess 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.
NAGS deficiency is a long-term debilitating and life-threatening disease that leads to mental retardation and is associated with a high mortality rate.
At the time of designation, NAGS deficiency 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 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 509,000,000 (Eurostat 2013).
At the time of designation, carglumic acid was authorised in the EU for the treatment of NAGS 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. The only cure for the disease was liver transplantation.
The sponsor has provided sufficient information to show that heterologous human adult liver-derived progenitor cells might be of significant benefit for patients with NAGS deficiency because early studies in experimental models show that it might lead to healthy liver cells that can produce the NAGS enzyme, thereby improving the treatment of patients with this condition. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
This medicine is an advanced-therapy medicine that belongs to the group called 'somatic-cell-therapy products'. These are medicines that contain cells or tissues that have been manipulated to change their biological characteristics so that they can be used to cure, diagnose or prevent a disease. The medicine is made up of progenitor (immature) cells derived from the liver of an adult donor ('heterologous'). When implanted into the liver of a patient, it is believed that these heterologous liver-derived progenitor cells will develop into mature, healthy liver cells that can produce the NAGS enzyme. The new cells are thereby expected to reduce the accumulation of ammonia and to relieve the symptoms of the disease.
The effects of heterologous human adult liver-derived progenitor cells have been evaluated in experimental models.
At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with urea-cycle disorders were ongoing.
At the time of submission, the medicine was not authorised anywhere in the EU for NAGS deficiency. Orphan designation of the medicine had been granted in the United States for urea-cycle disorders.
In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 13 June 2013 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.
Key facts
- Active substance
- heterologous human adult liver-derived progenitor cells
- Intended use
- Treatment of N-acetylglutamate synthetase (NAGS) deficiency
- Orphan designation status
- Positive
- EU designation number
- EU/3/13/1165
- Date of designation
- Sponsor
Cellaion
Review of designation
The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.
Update history
| Date | Update |
|---|---|
| May 2024 | The sponsorship was transferred to Cellaion in May 2024. |
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: