EU/3/19/2168 - orphan designation for treatment of maternally-inherited diabetes and deafness
(S)-6-hydroxy-2,5,7,8-tetramethyl-N-((R)-piperidine-3-yl)chroman-2-carboxamide hydrochloride
OrphanHuman
Overview
On 28 June 2019, orphan designation EU/3/19/2168 was granted by the European Commission to Khondrion B.V., the Netherlands, for (S)-6-hydroxy-2,5,7,8-tetramethyl-N-((R)-piperidine-3-yl)chroman-2-carboxamide hydrochloride (also known as KH176) 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.
Key facts
- Active substance
- (S)-6-hydroxy-2,5,7,8-tetramethyl-N-((R)-piperidine-3-yl)chroman-2-carboxamide hydrochloride
- Intended use
- Treatment of maternally-inherited diabetes and deafness
- Orphan designation status
- Positive
- EU designation number
- EU/3/19/2168
- Date of designation
- Sponsor
Khondrion BV
Transistorweg 5
6534 Nijmegen
Gelderland
The Netherlands
Tel. +31 243617505
E-mail: info@khondrion.com
Update history
| Date | Update |
|---|---|
| March 2023 | The sponsor's address was updated. |
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: