EU/3/10/841: Orphan designation for the treatment of non-24-hour sleep-wake disorders in blind people with no light perception

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.

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

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.

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.

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.

• 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.