EU/3/18/2033 - orphan designation for treatment of ornithine transcarbamylase deficiency
codon-optimised human ornithine transcarbamylase mRNA complexed with lipid-based nanoparticles
OrphanHuman
Overview
On 27 June 2018, orphan designation (EU/3/18/2033) was granted by the European Commission to Real Regulatory Limited, Ireland, for codon-optimised human ornithine transcarbamylase mRNA complexed with lipid-based nanoparticles (also known as MRT5201) for the treatment of ornithine transcarbamylase deficiency.
Please note that this product was withdrawn from the Union Register of orphan medicinal products in April 2021 on request of the Sponsor.
Ornithine transcarbamylase deficiency is one of the inherited disorders known as urea-cycle disorders, which cause ammonia to build up in the blood. Patients with ornithine transcarbamylase deficiency lack ornithine transcarbamylase, one of the liver enzymes 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 harmful at high levels, especially to the brain. Symptoms of the disease may appear in the first few days of life (particularly in boys) and include lethargy (lack of energy), vomiting, loss of appetite, seizures (fits) and coma, often leading to death. However, the age at which symptoms start is highly variable, particularly in females.
Ornithine transcarbamylase deficiency is a long-term debilitating and life-threatening disease that can alter brain function and is associated with poor overall survival.
At the time of designation, ornithine transcarbamylase deficiency affected approximately 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 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 28), Norway, Iceland and Liechtenstein. This represents a population of 517,400,000 (Eurostat 2018).
At the time of designation, glycerol phenylbutyrate (Ravicti) and sodium phenylbutyrate (Ammonaps, Pheburane) were 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 was used to manage the condition in some people.
The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with ornithine transcarbamylase deficiency. Laboratory studies show that it restores the levels of ornithine transcarbamylase in the liver, which is missing in patients affected by the condition. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
The medicine consists of genetic material (messenger RNA) containing the instructions that liver cells need to make the missing enzyme, ornithine transcarbamylase. The genetic material is enclosed in tiny fatty particles to protect it and help it enter liver cells. When given by infusion (drip) into a vein, the medicine is expected to enable liver cells to produce ornithine transcarbamylase and to reduce the symptoms caused by its deficiency.
The effects of the medicine have been evaluated in experimental models.
At the time of submission of the application for orphan designation, no clinical trials with the medicine in patients with ornithine transcarbamylase deficiency had been started.
At the time of submission, the medicine 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 24 May 2018 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
- codon-optimised human ornithine transcarbamylase mRNA complexed with lipid-based nanoparticles
- Intended use
- Treatment of ornithine transcarbamylase deficiency
- Orphan designation status
- Withdrawn
- EU designation number
- EU/3/18/2033
- Date of designation
- Sponsor
Transcrip Ireland Limited
Review of designation
The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.
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: