EU/3/19/2168: Orphan designation for the treatment of maternally-inherited diabetes and deafness

Maternally inherited diabetes and deafness is a type of diabetes inherited from the mother, often accompanied by hearing loss. Other symptoms include macular retinal dystrophy (an eye disorder that causes vision loss), muscle weakness, heart and kidney problems and constipation.

In most cases, the disease develops in early adulthood and is caused by mutations (changes) in the DNA (genetic material) of mitochondria (energy-producing components of cells). As a result, mitochondria do not function well and cells cannot perform their functions correctly. The disease affects the organs where cells are most active such as the pancreas, causing problems with the release of insulin into the blood and leading to diabetes. As mitochondria are also very active in the cochlea (part of the inner ear) it also affects hearing.

Maternally inherited diabetes and deafness is a long-term debilitating disease due to deafness and difficult to treat diabetes.
 

At the time of designation, maternally inherited diabetes and deafness affected less than 1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 52,000 people*, 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).

*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 518,400,000 (Eurostat 2019).

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of maternally inherited diabetes and deafness. Patients were given medicines for diabetes and hearing aids.

The defects in mitochondria that occur in maternally inherited diabetes and deafness are known to result in the production of toxic molecules containing oxygen that cause damage to cells (known as ‘oxidative stress’). The medicine is a small molecule capable of entering the cell where it acts as an antioxidant, reducing oxidative stress. This antioxidant activity is expected to reduce the symptoms of the disease.

The effects of (S)-6-hydroxy-2,5,7,8-tetramethyl-N-((R)-piperidine-3-yl)chroman-2-carboxamide hydrochloride 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 maternally inherited diabetes and deafness were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for the treatment of maternally inherited diabetes and deafness. Orphan designation of the medicine had been granted in the United States for the treatment of inherited mitochondrial respiratory chain diseases.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 23 May 2019, 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.