EU/3/14/1321 - orphan designation for treatment of Crigler-Najjar syndrome
Adeno-associated viral vector serotype 8 containing the human UGT1A1 gene (volrubigene ralaparvovec)
OrphanHuman
Overview
This medicine is now known as volrubigene ralaparvovec.
On 22 August 2014, orphan designation (EU/3/14/1321) was granted by the European Commission to Fondazione Telethon, Italy, for adeno-associated viral vector serotype 8 containing the human UGT1A1 gene for the treatment of Crigler-Najjar syndrome.
For a list of the administrative updates to this public summary of opinion please refer to the PDF document below.
Please note that this product was withdrawn from the Union Register of orphan medicinal products in March 2021 on request of the Sponsor.
Crigler-Najjar syndrome is a genetic disorder in which there is an accumulation of high amounts of toxic bilirubin in the body.
Bilirubin is a waste product that results from the breakdown of haemoglobin from old or damaged red blood cells. Normally bilirubin is converted in the liver to a less toxic, soluble form called 'conjugated' bilirubin that can be excreted into the bile and so removed from the body via the gut. However, patients with this condition lack the enzyme required to convert the bilirubin and as a result it accumulates in the liver and then in the blood stream and body tissues, where it can lead to damage.
Because of the yellow colour of bilirubin, jaundice, which is the yellowing of the skin and eyes, is usually seen within a few days of birth. The most severe complication is kernicterus, where bilirubin causes damage to the brain tissue that can lead to serious problems with muscle tone, movement, hearing and intellectual ability.
The condition is long-term debilitating and life threatening due to the development of kernicterus.
At the time of designation, Crigler-Najjar syndrome affected less than 0.1 in 10,000 people in the European Union (EU). This was 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 isbased 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. At the time of designation, this represented a population of 512,900,000 (Eurostat 2014).
At the time of designation, there was no satisfactory method of treatment authorised in the EU for patients with Crigler-Najjar syndrome. Some patients were given treatments such as phototherapy (using light of certain wavelengths to break down some of the bilirubin), blood transfusions and liver transplantation.
Crigler-Najjar syndrome is caused by mutations (defects) in a gene called UGT1A1, which is needed for the body to produce the enzyme that converts unconjugated bilirubin into the conjugated form that can be easily removed from the body. This medicine is made of a virus that contains a normal copy of the UGT1A1 gene. When given to the patient the virus is expected to carry the gene into the cells of the liver, enabling the cells to produce the required enzyme, thus reducing levels of bilirubin in the body and preventing development of symptoms.
The type of 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 in patients with Crigler-Najjar syndrome had been started.
At the time of submission, the medicine was not authorised anywhere in the EU for Crigler-Najjar syndrome 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 10 July 2014 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 8 containing the human UGT1A1 gene (volrubigene ralaparvovec)
- Intended use
- Treatment of Crigler-Najjar syndrome
- Orphan designation status
- Withdrawn
- EU designation number
- EU/3/14/1321
- Date of designation
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: