EU/3/18/2082 - orphan designation for treatment of Kabuki syndrome
5-{(1R,2R)-2-[(cyclopropylmethyl)amino]cyclopropyl}-N-(tetrahydro-2H-pyran-4-yl)thiophene-3-carboxamide monohydrochloride
OrphanHuman
Overview
On 19 November 2018, orphan designation (EU/3/18/2082) was granted by the European Commission to Takeda Pharma A/S, Denmark, for 5-{(1R,2R)-2-[(cyclopropylmethyl)amino]cyclopropyl}-N-(tetrahydro-2H-pyran-4-yl)thiophene-3-carboxamide monohydrochloride (also known as TAK-418) for the treatment of Kabuki syndrome.
The sponsor’s address was updated in August 2020.
Kabuki syndrome, or Nikawa-Kuroki syndrome, is a disorder usually caused by changes (mutations) in certain genes important for normal development. Children with the condition may be born with malformations of various organs, including a distinctive shape of the eyes, nose and ears. They have reduced intellectual and speech development and poor control over their muscles, and may suffer from heart problems and epilepsy. Their immune system (the body’s natural defences) is less effective, leading to frequent infections.
Kabuki syndrome is a long-term debilitating condition due to the effects on the nervous system and heart.
At the time of designation, Kabuki syndrome affected approximately 1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 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 517,400,000 (Eurostat 2018).
At the time of designation no satisfactory methods were authorised for treatment of Kabuki syndrome in the EU. Patients were managed with treatment aimed at relieving the various symptoms of the condition.
This medicine blocks the action of an enzyme called lysine-specific demethylase-1 (LSD-1), which among other actions works in the cells of the brain to regulate genes involved in learning and memory. It is expected that by blocking the action of LSD-1 the medicine will help to counteract the reduced development and function of brain cells seen in patients with Kabuki syndrome.
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 Kabuki syndrome had been started.
At the time of submission, the medicine was not authorised anywhere in the EU for Kabuki syndrome. Orphan designation of the medicine had been granted in the United States for this condition.
In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 11 October 2018 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
- 5-{(1R,2R)-2-[(cyclopropylmethyl)amino]cyclopropyl}-N-(tetrahydro-2H-pyran-4-yl)thiophene-3-carboxamide monohydrochloride
- Intended use
- Treatment of Kabuki syndrome
- Orphan designation status
- Withdrawn
- EU designation number
- EU/3/18/2082
- Date of designation
- Sponsor
Takeda Pharma A/S
Review of designation
The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.
Update history
| Date | Update |
|---|---|
| November 2022 | Please note that this product was withdrawn from the Union Register of orphan medicinal products in November 2022 on request of the Sponsor. |
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:
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: