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Orphan designation

On 17 January 2018, orphan designation (EU/3/17/1971) was granted by the European Commission to Edison Orphan Pharma BV, The Netherlands, for vatiquinone (also known as alpha-tocotrienol quinone) for the treatment of RARS2 syndrome.

What is RARS2 syndrome?

RARS2 syndrome (or pontocerebellar hypoplasia type 6) is an inherited disorder of the mitochondria, the structures inside cells that supply them with energy. It is caused by a mutation (change) in the gene that enables production of an enzyme called mitochondrial arginyl-transfer RNA synthetase (RARS2). This enzyme is needed for the mitochondria to work normally. Patients with RARS2 syndrome develop rapidly progressive damage to the brain in the early weeks or years of life.

RARS2 syndrome is a debilitating and life-threatening disorder due to hard-to-control seizures (fits), recurring infections, paralysis and developmental delay. The condition is usually fatal in early childhood.

What is the estimated number of patients affected by the condition?

At the time of designation, RARS2 syndrome affected less than 0.001 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 50 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. This represents a population of 515,700,000 (Eurostat 2017).

What treatments are available?

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of RARS2 syndrome. Treatment was mainly supportive, including medicines to treat seizures, antibiotics for infections, and dietary and nutritional support.

How is this medicine expected to work?

In patients with RARS2 syndrome, the abnormality in the mitochondria is thought to result in increased production of unstable compounds containing oxygen (oxidative stress) that damage cells, and lowered levels of substances such as glutathione that normally protect cells. Vatiquinone is a derivative of vitamin E that is expected to enter the cells of the brain and help protect them against oxidative stress by increasing production of glutathione. It is expected that this will slow the damage to the cells and help reduce symptoms of the condition.

What is the stage of development of this medicine?

The effects of vatiquinone have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with vatiquinone in patients with RARS2 syndrome had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for RARS2 syndrome. Orphan designation of vatiquinone had been granted in the EU for Leigh syndrome, another condition related to abnormal function of mitochondria.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 7 December 2017 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:
  • 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.

Name Language First published Last updated
EU/3/17/1971: Public summary of opinion on orphan designation: Vatiquinone for the treatment of RARS2 syndrome (English only) 2018-03-12  

Key facts

Product details for <p align="left">Vatiquinone</p>
Active substanceVatiquinone
Medicine Name
Disease/conditionTreatment of RARS2 syndrome
Date of decision17/01/2018
Orphan decision numberEU/3/17/1971

Review of designation

Sponsor's contact details

Edison Orphan Pharma BV
Marconistraat 16
Room 9.01
3029 AK
The Netherlands
Tel. + 31 6204 43098

Patients' organisations

For contact details of patients’ organisations whose activities are targeted at rare diseases, see:

  • Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe;
  • European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.