EU/3/17/1947: Orphan designation for the treatment of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes

MELAS is an inherited disease caused by genetic abnormalities in the mitochondria, the energy-producing components within cells. Symptoms of the condition usually appear in childhood and include muscle weakness and pain, headaches, loss of appetite, vomiting and seizures (fits). By the age of 40, most patients experience stroke-like episodes that can lead to vision loss, problems with movement and loss of intellectual function.

The condition is life threatening and debilitating in the long term due to symptoms such as seizures, stroke-like episodes, and the recurring headaches, vomiting and weakness.

At the time of designation, MELAS affected approximately 0.06 in 10,000 people in the European Union (EU). This was equivalent to a total of around 3,000 people¹, and is below the ceiling for orphan designation, which is 5 people in 10,000. This is based 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 515,700,000 (Eurostat 2017).

No satisfactory methods of treatment were authorised in the EU at the time of orphan designation. Patients received supportive therapy to deal with the symptoms.

The medicine works by combining with an enzyme widely present in body cells and triggering the production of NAD⁺ inside the cell. The increase in NAD⁺ triggers the activation of several proteins and cell processes which are expected to improve the function of mitochondria. Because MELAS is linked to abnormalities in the mitochondria, improvements in mitochondrial function are expected to help reduce symptoms of the condition.

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 MELAS had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for MELAS 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 31 October 2017 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.