EU/3/16/1673: Orphan designation for the treatment of fragile X syndrome

Fragile X syndrome is an inherited disease characterised by moderate to severe learning disability. Other symptoms include difficulty communicating and socialising, anxiety, hyperactivity, and repetitive and stereotyped behaviours.

The disease is caused by a defect in a gene on the X chromosome. The gene is responsible for the production of a protein called fragile X mental retardation protein (FMRP), which is necessary for the development of the brain. In patients with fragile X syndrome, the defective gene cannot produce normal levels of the FMRP protein and this leads to learning disability and other neurological symptoms. Women are normally less severely affected than men, because they have a second X chromosome that usually has a normal copy of the gene.

Fragile X syndrome is a long-term debilitating disease because of the behavioural problems and learning disabilities it causes.

At the time of designation, fragile X syndrome affected approximately 2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 103,000*, 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 513,700,000 (Eurostat 2016).

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of fragile X syndrome. Patients were given general support, such as behavioural therapy and special education, and in some cases, antidepressants, stimulants and antipsychotics were used to treat the symptoms of the disease. Genetic counselling (discussion of the risks of passing on the condition to children) was recommended for families with a history of fragile X syndrome.

This medicine is intended to increase the transmission of GABA between nerve cells. GABA is a substance that reduces the activity of brain cells. In fragile X syndrome GABA transmission is impaired, leading to the behavioural problems associated with the disease.

By binding to GABA transporters on the nerve cells and blocking the action of enzymes that break down GABA, the medicines is expected to increase the effects of GABA in the nerve cells and thereby reduce 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, clinical trials with the medicine in patients with fragile X syndrome were ongoing.

At the time of submission, the medicine was authorised in Hungary, Italy, Lithuania and Portugal for treating alcohol dependence and fatty liver due to alcoholism.

At the time of submission, the medicine was not authorised anywhere in the EU for fragile X syndrome. Orphan designation had been granted in the United States for fragile X syndrome.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 19 May 2016 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.