EU/3/20/2267 - orphan designation for treatment of progressive familial intrahepatic cholestasis
Adeno-associated viral vector serotype 3B encoding human multidrug resistance protein 3A
OrphanHuman
Overview
On 22 April 2020, orphan designation EU/3/20/2267 was granted by the European Commission to Vivet Therapeutics S.A.S., France, for adeno-associated viral vector serotype 3B encoding human multidrug resistance protein 3A (also known as VTX-803) for the treatment of progressive familial intrahepatic cholestasis.
Progressive familial intrahepatic cholestasis is an inherited condition that causes progressive liver disease, which normally leads to liver failure. In progressive familial intrahepatic cholestasis, bile acids, essential components of bile (a fluid produced by the liver which helps digestion), build up in liver cells, becoming toxic to the liver and causing cirrhosis (scarring). Symptoms usually begin in infancy and include severe itching, jaundice (yellowing of the skin and eyes), delayed growth, pancreatitis (inflammation of the pancreas) and bleeding inside the stomach or the gut. At later stages, high blood pressure in the vein that supplies blood to the liver and liver failure will occur.
Progressive familial intrahepatic cholestasis is a long-term debilitating and life-threatening condition because, when the disease progresses, it may lead to liver cirrhosis and liver failure, and may increase the risk of liver cancer. Patients often need liver transplantation.
At the time of designation, progressive familial intrahepatic cholestasis affected approximately 0.2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 10,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).
* 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, Iceland, Liechtenstein, Norway and the United Kingdom. This represents a population of 519,200,000 (Eurostat 2020).
At the time of designation, ursodeoxycholic acid (UDCA) was authorised in France for a type of the condition called progressive familial intrahepatic cholestasis type III. Several medicines, including UDCA, were also used in the EU to treat the itching.
The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with progressive familial intrahepatic cholestasis because early laboratory data indicated that the medicine could improve liver function in the long term, potentially avoiding the need for continuous daily treatment. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
Progressive familial intrahepatic cholestasis type III is caused by mutations (changes) in the gene for a protein known as multidrug resistance protein 3 (MDR3). MDR3 helps to transport certain lipids that inactivate bile acids and help to protect liver cells from toxic substances in the bile fluid. Because of the mutations, MDR3 does not work properly and toxic bile acids build up in liver cells. This medicine is made of a virus that contains a normal copy of the gene for MDR3. When given to the patient, the virus is expected to carry the gene into the cells of the liver, enabling the cells to produce working MDR3, thus reducing build-up of toxic bile acids and preventing development of symptoms.
The virus used in this medicine ('adeno-associated virus') does not cause disease in humans.
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 had been started.
At the time of submission, the medicine was not authorised anywhere in the EU for the treatment of progressive familial intrahepatic cholestasis or designated as an orphan medicinal product elsewhere for this condition.
In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 19 March 2020, 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
- Adeno-associated viral vector serotype 3B encoding human multidrug resistance protein 3A
- Intended use
- Treatment of progressive familial intrahepatic cholestasis
- Orphan designation status
- Positive
- EU designation number
- EU/3/20/2267
- Date of designation
- Sponsor
Vivet Therapeutics SAS
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: