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Orphan designation

On 15 April 2011, orphan designation (EU/3/11/858) was granted by the European Commission to Lakeside Regulatory Consulting Services Ltd, United Kingdom, for R-baclofen for the treatment of fragile X syndrome.

What is fragile X syndrome?

Fragile X syndrome is a genetic disease characterised by moderate to severe mental retardation. Other symptoms include social withdrawal, 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 the FMRP protein and this leads to the mental retardation and other neurological symptoms. Men are usually more severely affected than women as they have only one X chromosome.

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

What is the estimated number of patients affected by the condition?

At the time of designation, fragile X syndrome affected approximately 2 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 101,000 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 27), Norway, Iceland and Liechtenstein. This represents a population of 506,300,000 (Eurostat 2011).

What treatments are available?

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 the condition on to children) was recommended for families with a history of fragile X syndrome.

How is this medicine expected to work?

FMRP acts as a ‘brake’ in the brain processes that involve certain receptors called ‘glutamate receptors’. The lack of FMRP in patients with fragile X syndrome results in an overactivation of these processes, which eventually affects brain function.

R-baclofen activates a different type of receptors (GABA-B receptors) that are expected to make up for the lack of FMRP by decreasing the activation of glutamate receptors. This is expected to help correct the brain dysfunction in patients with fragile X syndrome.

It is also thought that R-baclofen could work by reducing the excessive transmission of signals in the amygdala, the region in the brain involved in the processing and memory of emotional reactions.

What is the stage of development of this medicine?

The effects of R-baclofen have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with R-baclofen in patients with fragile X syndrome were ongoing.

At the time of submission, R-baclofen was not authorised anywhere in the EU for fragile X syndrome. Orphan designation of the medicine had been granted in the United States of America for the treatment of the behavioural abnormalities associated with fragile X syndrome.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 12 January 2011 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:
  • 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

Product details for <p>R-baclofen</p>
Active substanceR-baclofen
Medicine Name
Disease/conditionTreatment of fragile X syndrome
Date of decision15/04/2011
Orphan decision numberEU/3/11/858

Review of designation

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.

Sponsor’s contact details:

Lakeside Regulatory Consulting Services Ltd
20 Lakeside
Bucks HP19 0FX
United Kingdom
Telephone: +44 7841026283
Telefax: +44 1296 394276

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.
  • European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.