EU/3/18/2082: Orphan designation for the treatment of Kabuki syndrome

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).

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.