EU/3/16/1772 - orphan designation for treatment of Crigler-Najjar syndrome
Adeno-associated viral vector serotype 8 containing the human UGT1A1 gene (volrubigene ralaparvovec)
OrphanHuman
Overview
Please note that this product was withdrawn from the Union Register of orphan medicinal products in January 2021 on request of the sponsor.
On 18 November 2016, orphan designation (EU/3/16/1772) was granted by the European Commission to Audentes Therapeutics UK Limited, United Kingdom, for adeno-associated viral vector serotype 8 containing the human UGT1A1 gene (also known as AT342) for the treatment of Crigler-Najjar syndrome.
The sponsorship was transferred to Audentes Therapeutics Netherlands B.V., Netherlands in May 2019.
This medicine is now known as volrubigene ralaparvovec.
Crigler-Najjar syndrome is an inherited disorder in which harmful levels of bilirubin build up in the body. Bilirubin is a waste product of the breakdown of haemoglobin from old or damaged red blood cells.
Normally bilirubin is converted in the liver to a less toxic form called 'conjugated' bilirubin that is removed from the body via the gut. However, patients with Crigler-Najjar syndrome lack the enzyme that converts bilirubin into the less toxic form and as a result it builds up in the liver and then in the blood stream and body tissues, where it can cause 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 damages brain tissue and leads 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 people1, 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).
1Disclaimer: 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 513,700,000 (Eurostat 2016).
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) and liver transplantation.
Crigler-Najjar syndrome is caused by mutations (changes) in a gene called UGT1A1. This gene is needed for the liver to produce the enzyme that converts unconjugated bilirubin into the conjugated form that can be 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 virus used in this medicine ('adeno-associated virus') does not cause disease in humans.
At the time of submission of the application for orphan designation, the evaluation of the effects of the medicine in experimental models was ongoing.
At the time of submission, 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. Orphan designation for this medicine has been granted in the United States for this condition.
In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 6 October 2016 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/3/16/1772
- Date of designation
- Sponsor
Audentes Therapeutics Netherlands B.V.
Schiphol Boulevard 359
Schiphol
Noord-Holland 1118 BJ
The Netherlands
E-mail: info@audentestx.com
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: