Hetlioz - opinion on variation to marketing authorisation
Opinion
EMA has issued an opinion on a change to this medicine's authorisation
tasimelteon
Post-authorisationHuman
Hetlioz is a medicine used to treat totally blind adults with non-24-hour sleep-wake disorder. Non-24-hour sleep-wake disorder is a condition that occurs almost exclusively in people who are completely blind, where patients have sleep patterns that are not synchronised with day and night and often follow a cycle that is longer than the standard 24-hour clock. As a result, patients fall asleep and wake up at unusual times.
Hetlioz contains the active substance tasimelteon.
The company applied to extend the use of Hetlioz to add the treatment of nighttime sleep disturbance in children aged 3 to 15 years old with Smith-Magenis syndrome. Smith-Magenis syndrome is a rare hereditary disorder characterised by developmental delay, behavioural problems, and sleep disturbance. Sleep problems in people with Smith-Magenis syndrome are caused by an abnormal production pattern of melatonin (a hormone that plays a key role in co-ordinating the body’s sleep-wake cycle).
Melatonin is involved in coordinating the body’s sleep cycle by acting on cells in specific areas of the brain and helping to bring about sleep. Its levels in the blood normally increase after the onset of darkness and peak in the middle of the night. The active substance in Hetlioz, tasimelteon, acts on the same receptors as melatonin to promote sleep and regulate sleep patterns. By taking it at a suitable time each day it can help to reset the sleep-wake cycle to more standard timing.
In Smith-Magenis syndrome, Hetlioz was expected to work in the same way as it does in its existing use.
The company presented the results of a study involving 26 people with Smith-Magenis syndrome who were experiencing nighttime sleep disturbance (11 children aged 3 to 15 years and 15 adults and adolescents aged 16 and older). The study compared the effect of Hetlioz on sleep disturbance with that of placebo (a dummy treatment) over 4 weeks. The main measure of effectiveness was an improvement in nighttime sleep based on average sleep quality and average total sleep time, evaluated by caregivers using a post-sleep questionnaire.
The Agency considered that there were concerns about the design of the study, the statistical analysis of the results and the way the study had been conducted, which resulted in uncertainties in the observed treatment effects. There was also uncertainty as to how well the safety of Hetlioz in children with Smith-Magenis syndrome had been investigated due to issues relating to the design of the study and how it had been carried out.
Therefore, the Agency’s opinion was that the benefits and risks of Hetlioz in the treatment of children aged to 3 to 15 years with Smith-Magenis syndrome could not be established. Hence, the Agency recommended refusing the change to the marketing authorisation.
There are no consequences for Hetlioz in its authorised use for non-24-hour sleep-wake disorder.