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 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 along with implications to many physiologic and metabolic processes and organ systems. One important part of the circadian rhythm is melatonin and melatonin receptors in the suprachiasmatic nucleus. 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. Stimulation of Melatonin receptors in the suprachiasmatic nucleus and in peripheral tissues such as the retina and lenses of the eyes are partially responsible for initiating drowsiness and sleep.

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.

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.

Vanda Pharmaceuticals anticipates a New Drug Application (NDA) will be filed with the Food and Drug Administration (FDA) in mid 2011. This drug is sometimes referred to as BMS-214,778. Though FDA approval time of NDA has average of 24 months, a similar drug ramelteon (Rozerem - Takeda Pharmaceuticals) was approved in July 2005, 8 months after a September 2004 filing. If the same pattern is followed, Tasimelteon may be approved as early as the first quarter of 2012.