EU/3/16/1755

On 14 October 2016, orphan designation (EU/3/16/1755) was granted by the European Commission to Therapicon Srl, Italy, for the melatonin for the treatment of Smith-Magenis syndrome.

What is Smith-Magenis syndrome?

Smith-Magenis syndrome is a disorder with a variety of features including intellectual disability, speech and language delay, distinctive facial features, difficulty sleeping and behavioural problems. In same patients, organ malformations are present, affecting mostly the heart and kidneys. The severity of the disorder varies from one person to another.

The disorder is caused by the loss or damage of a gene called retinoic acid-induced 1. This genetic abnormality is not inherited from the parents but seems to occur spontaneously.

Smith-Magenis syndrome is a long-term debilitating disease because it causes intellectual disability and behavioural problems.

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

At the time of designation, Smith-Magenis syndrome affected less than 1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 51,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

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* 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).

What treatments are available?

At the time of designation, no medicines were authorised in the EU for the treatment of Smith-Magenis syndrome. Patients were given general support, such as behavioural and speech therapy.

How is this medicine expected to work?

Melatonin is a natural hormone that helps encourage and regulate sleep. Patients with Smith-Magenis syndrome have difficulty sleeping at night but are sleepy during the day. This is because their levels of melatonin reach their peak during the day, instead of the middle of the night.

By giving additional melatonin at night its levels can be increased, helping patients to sleep. This is combined with another medicine, acebutolol hydrochloride given in the morning, which is expected to help patients stay awake during the day. In this way, the two medicines would help to normalise the sleep cycle of patients with Smith-Magenis syndrome.

What is the stage of development of this medicine?

The sponsor has provided data from the published literature to support its application for orphan designation.

At the time of submission of the application for orphan designation, no clinical trials with melatonin in patients with Smith-Magenis syndrome had been started.

At the time of submission, melatonin was not authorised anywhere in the EU for Smith-Magenis 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 8 September 2016 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.