EU/3/20/2393: Orphan designation for the treatment of Pitt-Hopkins syndrome

Pitt-Hopkins syndrome is a condition that mainly affects the brain. It is caused by a change in the TCF4 gene needed to make a protein called transcription factor 4 (TCF4) that is essential for normal development of the brain. Children with this condition have delayed development, intellectual disability, severe speech defects and breathing problems. Other symptoms include repetitive behaviours and problems with social communication, constipation, severe short-sightedness, sleep problems and seizures (fits).

Pitt-Hopkins syndrome is a long-term debilitating condition due to the severe intellectual disability, breathing problems, seizures, gastrointestinal problems, and the tendency to self-injury.

At the time of designation, Pitt-Hopkins syndrome affected approximately 0.3 in 10,000 people in the European Union (EU). This was equivalent to a total of around 16,000 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).

*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, Iceland, Liechtenstein, Norway and the United Kingdom. This represents a population of 519,200,000 (Eurostat 2020).

At the time of designation, no medicines were authorised in the EU for the treatment of Pitt-Hopkins syndrome. Treatments were aimed at reducing the symptoms of the disease and included physical and speech therapy, and medicines for epilepsy and for gastrointestinal problems.

In patients with Pitt-Hopkins syndrome, lack of TCF4 means the brain cannot produce proteins needed to form synapses, the communication connections between nerve cells. The medicine is similar to a part of IGF-1, a substance in the brain that is essential for synapse formation and brain development. The medicine controls IGF-1 levels and also prevents inflammation in the brain. This is expected to help the brain form new synapses and keep them working, thereby reducing some 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 Pitt-Hopkins syndrome had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for the treatment of Pitt-Hopkins syndrome. Orphan designation of the medicine had been granted in the United States for Pitt-Hopkins syndrome.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 3 December 2020, 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.