EU/3/14/1336

On 15 October 2014, orphan designation (EU/3/14/1336) was granted by the European Commission to Khondrion BV, the Netherlands, for (S)-6-Hydroxy-2,5,7,8-tetramethyl-N-((R)-piperidin-3‑yl)chroman-2-carboxamide hydrochloride for the treatment of Leigh syndrome.

What is Leigh syndrome?

Leigh syndrome, also known as subacute necrotising encephalomyelopathy, is an inherited disease of the brain and the nervous system leading to problems such as poor motor function (movement), weakness, lack of muscle tone and difficulty breathing. Symptoms typically start before the age of 12 months. The disease has many genetic causes, all of which are linked to defects in the mitochondria, the energy-producing components within cells, which lead to the death of nerve cells.

Leigh syndrome is debilitating and life threatening due to progressive worsening of nervous system function as well as problems with heart, kidney and hormonal glands.

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

At the time of designation, Leigh syndrome affected less than 1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 51,000 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).

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*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 511,100,000 (Eurostat 2014).

What treatments are available?

At the time of designation, there were no satisfactory methods of treatment authorised in the EU for Leigh syndrome. Patients received supportive therapy to deal with the symptoms, such as mechanical support with breathing, vitamins and supplements.

How is this medicine expected to work?

The defects in mitochondria that occur in Leigh syndrome are known to result in the production of ‘free radicals’, molecules that cause damage to cells (known as ‘oxidative stress’). The medicine is a small molecule which is capable of entering the cell and acts as an antioxidant, reducing oxidative stress. This antioxidant activity is expected to prevent nerve cell death, thereby reducing the symptoms of the disease.

What is the stage of development of this medicine?

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 Leigh syndrome had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for Leigh 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 4 September 2014 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.

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.