EU/3/10/841

  • Email
  • Help

Orphan designation

On 23 February 2011, orphan designation (EU/3/10/841) was granted by the European Commission to Vanda Pharmaceuticals Limited, United Kingdom, for tasimelteon for the treatment of non-24-hour sleep-wake disorder in blind people with no light perception.

For a list of the administrative updates to this public summary of opinion please refer to the PDF document below.

What is non-24-hour sleep-wake disorder?

Non-24-hour sleep-wake disorder is a condition where patients have sleep patterns that are not adjusted to the standard 24-hour clock. They fall asleep and wake up at different times compared with the general population, often in a pattern that is closer to a 25-hour clock. As a result, they have problems adjusting to the standard timetable of everyday life, often being awake or asleep at abnormal times.

The way the body adjusts to the 24-hour clock is closely linked to the pattern of daylight and night of a normal day, and people who do not perceive light, such as blind people are more likely to suffer from the disorder.

Non-24-hour sleep-wake disorder is a long-term debilitating disease because of the excessive daytime sleepiness that affects quality of life and ability to function normally in a social environment.

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

At the time of designation, non-24-hour sleep-wake disorder in blind people with no light perception affected between 1.5 and 2.2 in 10,000 people in the European Union (EU). This was equivalent to a total of between 76,000 and 112,000 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).


*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. At the time of designation, this represented a population of 507,700,000 (Eurostat 2011).

What treatments are available?

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of non-24-hour sleep-wake disorder. Medicines were used to help patients sleep (such as benzodiazepine) or stay awake (caffeine) but none were specifically authorised for the condition.

How is this medicine expected to work?

A hormone called ‘melatonin’ plays a key role in co-ordinating the body’s sleep cycle by acting on receptors in specific areas of the brain. Melatonin is produced by a gland in the brain called the pineal gland during the hours of darkness, and blood levels of the hormone are high at night and low during the day.

Tasimelteon is expected to work as a ‘melatonin-receptor agonist’. This means that it attaches to the receptors that melatonin normally attaches to. By attaching itself to these receptors, it is expected to work in the same way as melatonin in promoting sleep and regulating sleep patterns.

What is the stage of development of this medicine?

The effects of tasimelteon have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with tasimelteon in the treatment of non-24-hour sleep-wake disorder in blind people with no light perception were ongoing.

At the time of submission, tasimelteon was not authorised anywhere in the EU for non-24-hour sleep-wake disorder in blind people with no light perception. Orphan designation had been granted in the United States of America for non-24 hour sleep/wake disorder in blind individuals without light perception.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 10 November 2010 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>Tasimelteon</p>
Active substanceTasimelteon
Medicine NameHetlioz
Disease/conditionTreatment of non-24-hour sleep-wake disorder in blind people with no light perception
Date of decision23/02/2011
OutcomePositive
Orphan decision numberEU/3/10/841

Review of designation

During its meeting of 12 to 13 May 2015, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/10/841 for Hetlioz (tasimelteon) as an orphan medicinal product for thefor the treatment of non-24-hour sleep-wake disorder. The COMP assessed whether, at the time of marketing authorisation, the medicinal product still met the criteria for orphan designation. The Committee looked at the seriousness and prevalence of the condition, and the existence of other methods of treatment. The COMP recommended that the orphan designation of the medicine be maintained*.

*The maintenance of the orphan designation at time of marketing authorisation would, except in specific situations, give an orphan medicinal product 10 years of market exclusivity in the EU. This means that in the 10 years after its authorisation similar products with a comparable therapeutic indication cannot be placed on the market.

Life-threatening or long-term debilitating nature of the condition

The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Hetlioz for ‘treatment of non-24-hour sleep-wake disorder in totally blind adults’.

During the review of the orphan designation for Hetlioz, the COMP noted that the original orphan condition, which was ‘non-24-hour sleep-wake disorder in blind people with no light perception’, is a subset of the condition ‘non-24-hour sleep-wake disorder’. The COMP concluded that the orphan condition should be amended to the latter, in line with the current classification of the condition.

The indication recommended by the CHMP falls within the scope of the amended orphan indication.

The COMP concluded during its review that there had been no change in the seriousness of the condition since the orphan designation in 2011. Non-24-hour sleep-wake disorder is a condition that is long-term debilitating because of the excessive daytime sleepiness that affects the patient’s quality of life and their ability to carry out daily activities.

Prevalence of the condition

The sponsor provided updated information on the prevalence of non-24-hour sleep-wake disorder based on data from the WHO and published literature.

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of non-24-hour sleep-wake disorder is below the ceiling for orphan designation, which is 5 people in 10,000. At the time of the review of the orphan designation, the prevalence was estimated to be less than 3.3 people in 10,000. This is equivalent to a total of around 169,000 people in the EU.

Existence of other methods of treatment

The COMP noted that, at the time of the review of the orphan designation, no treatments were authorised in the EU for the treatment of non-24-hour sleep-wake disorder.

Conclusions

Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Hetlioz still meets the criteria for designation as an orphan medicinal product and that it should remain in the Community Register of Orphan Medicinal Products.

Related information

Sponsor’s contact details

Vanda Pharmaceuticals Limited
222 Regent Street
London W1B 5TR
United Kingdom
Tel. +44 (0)20 7903 5000
Fax +44 (0)20 7903 5333

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.