Tasimelteon for Insomnia

Sleep Disorders

Tasimelteon is a new drug under investigation for the treatment of insomnia. It has demonstrated ability to reset the circadian rhythm - it's a "chronobiotic" - and restore normal sleep patterns by stimulation of the melatonin receptors in the suprachiasmatic nucleus or biologic clock area of the brain. This is useful in patients who experience insomnia due to shift work or jet lag. It is also useful in persons with delayed sleep phase syndrome (falling asleep and waking too late), advanced sleep phase syndrome (falling asleep and waking too early) along with non-24 hour sleep-wake syndrome such as occurs in the blind due to a lack of light sensitivity.

The circadian rhythm is a complex system of hormone regulation which regulates sleep, wakefulness, and mood and influences many physiologic and metabolic processes and organ systems. An important part of the circadian rhythm is melatonin and melatonin receptors in the suprachiasmatic nucleus (a part of the brain). In a well-regulated circadian rhythm, levels of melatonin start to rise each evening with the onset of darkness, peak around midnight when a person should be normally asleep and fall dramatically during daylight hours. The circadian cycle initiates drowsiness and sleep partly by stimulating melatonin receptors in the suprachiasmatic nucleus and in tissues such as the retina and lenses of the eyes.

In December 2008, Vanda Pharmaceuticals released positive results of phase II and III clinical studies regarding Tasimelteon. Subjects were asked to initiate sleep 5 hours before usual bedtime, simulating a 5 hour shift in time zones. Tasimelteon was shown to be better than placebo in the initiation of sleep and also led to a quicker return of the normal circadian rhythm with restoration of normal peak times of melatonin production. Harvard Medical School researchers wrote up the research here: http://www.ncbi.nlm.nih.gov/pubmed/19054552

Unlike benzodiazepines such as diazepam (Valium) and newer drugs such as zolpidem (Ambien) Tasimelteon has demonstrated no affinity for the GABA receptor. Due to lack of GABA activity it will not be useful as sedative, anti-seizure agent, antianxiety agent or muscle relaxant but will also not have the potential for abuse or dependence, symptoms of withdrawal or rebound insomnia. Because of the lack of abuse potential, Tasimelteon will likely emerge as a non-scheduled prescription and not as a controlled substance.

A writer from the Sleep Disorders Center of Georgia says more information on the drugs pharmacokinetics and pharmacodynamics should be developed "before tasimelteon can be considered a worthwhile addition to the available treatments for insomnia".

In 2010 the FDA designated tasimelteon an orphan drug for blind people with Non-24-Hour Sleep-Wake Disorder. The European Medicines Agency also approved it as an orphan drug in 2011.

Will tasimelteon become available for the general public? It seems to have hit a stumbling block Vanda Pharmaceuticals had earlier announced plans to file a New Drug Application (NDA) for general use for insomnia, but recent news released by the company does not mention that anymore. They have announced a clinical trial for tasimelteon for treatment of depression. It appears this is a path they are trying to take to monetize the drug. For now, as far as we can tell, the plan to seek FDA approval for tasimelteon for general insomnia has been pushed back and the company says it will file an NDA in 2013.