EU/3/13/1143 - orphan designation for treatment of acute liver failure
immortalised human C3A hepatoblastoma cells
OrphanHuman
Overview
On 19 June 2013, orphan designation (EU/3/13/1143) was granted by the European Commission to Vital Therapies Limited, United Kingdom, for immortalised human C3A hepatoblastoma cells for the treatment of acute liver failure.
The sponsorship was transferred to MWB Consulting S.A.R.L., France, in May 2019.
Acute liver failure is the sudden loss of normal liver functions in a patient with a previously normal liver and without evidence of chronic (long-term) liver disease.
The most common first sign of liver failure is jaundice (yellowing of the skin). Acute liver failure brings serious complications such as bruising and bleeding due to impaired blood clotting, cerebral oedema (swelling around the brain), convulsions (fits) and coma.
The most common causes of acute liver failure in Europe are toxic damage (for example due to consumption of large amounts of alcohol or overdose of medicines such as paracetamol) or viral hepatitis (an infectious disease that affects the liver).
Acute liver failure is a life-threatening disease because of its damaging effects on the liver, brain and other organs.
At the time of designation, acute liver failure affected less than 1 person in 10,000 per year in the European Union (EU). This was equivalent to a total of fewer than 50,000 people per year*, and is below the ceiling for orphan designation. 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, the main treatment option for acute liver failure was liver transplantation. Patients with acute liver failure caused by paracetamol overdose were treated with N-acetylcysteine.
The sponsor has provided sufficient information to show that immortalised human C3A hepatoblastoma cells might be of significant benefit for patients with acute liver failure, because early studies show that they may temporarily relieve some of the symptoms of the condition and delay the need for liver transplantation. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
This product consists of a cartridge containing many fine tubes lined with membranes, on the other side of which are cells derived from a type of liver tumour (hepatoblastoma). The cells are able to function like normal liver cells, but they can survive and grow inside the device (hence they are called 'immortalised').
The device is expected to act as a temporary 'artificial liver' outside the patient's body. The patient's blood is continuously drawn from a vein, and the plasma (the liquid part of the blood) is separated and passes through the tubes in the cartridge.
Toxins that affect the brain in patients with liver failure can pass through the membrane to the hepatoblastoma cells, which break them down. In turn, the cells produce substances needed for blood clotting and other functions, which can pass back into the plasma. The plasma is then recombined with the other parts of the blood and the blood is returned to the patient. In this way, the product is expected to carry out the liver's essential functions, thereby relieving the symptoms of acute liver failure.
The effects of the medicine have been evaluated in experimental models.
At the time of submission of the application for orphan designation, clinical trials with immortalised human C3A hepatoblastoma cells in patients with acute liver failure were ongoing.
At the time of submission, the medicine was not authorised anywhere in the EU for acute liver failure. Orphan designation had been granted in the United States for the treatment of acute liver failure.
In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 15 May 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
- immortalised human C3A hepatoblastoma cells
- Intended use
- Treatment of acute liver failure
- Orphan designation status
- Positive
- EU designation number
- EU/3/13/1143
- Date of designation
- Sponsor
MWB Consulting S.A.R.L.
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: