EU/3/15/1531: Orphan designation for the treatment of Rett syndrome

Rett syndrome is a genetic disease that is caused by abnormalities in the MECP2 gene, which is important for the normal functioning of nerve cells. It almost exclusively affects girls. Although the disease is genetic, most girls affected (over 95%) do not inherit it from their parents.

Girls with Rett syndrome lose their ability to properly control their muscles, have feeding difficulties and learning disabilities. The features first start to appear between six and 18 months of age. Other symptoms include difficulty breathing, irregular heartbeat, sleeping problems, constipation, repetitive hand movements and seizures (fits).

Rett syndrome is a seriously debilitating and life-threatening disease mainly because of problems with breathing and the heart rhythm.

At the time of designation, Rett syndrome affected approximately 1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 51,000 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 512,900,000 (Eurostat 2015).

At the time of designation no authorised treatments were available for Rett syndrome. Girls with the disease were given physiotherapy, speech therapy and nutritional support to help relieve the symptoms of the disease. Medicines to control seizures were also used, as well as laxatives and painkillers.

Girls with Rett syndrome may have low levels of serotonin, a substance in the brain and spinal cord that helps maintain a normal breathing rhythm. Sarizotan acts on certain receptors for serotonin called 5-HT_1A. By stimulating these receptors, sarizotan replaces the effect of some of the missing serotonin in the brain and spinal cord. This is expected to help restore normal breathing rhythm in girls with Rett syndrome.

The effects of sarizotan have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with sarizotan in patients with Rett syndrome had been started.

At the time of submission, sarizotan was not authorised anywhere in the EU for Rett syndrome or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 18 June 2015 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.