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Tasimelteon (Hetlioz®): First FDA Approved Pharmacologic Agent for Treatment of Non-24 in Completely Blind Individuals

By: Beatrisa Popovitz, Senior Staff Editor

On January 31st 2014, the FDA announced the release of a revolutionary new drug, tasimelteon (Hetlioz®). Tasimeleton is the first developed treatment of non-24-hour sleep-wake cycle syndrome in blind individuals.1 Formulated by Vanda Pharmaceuticals Inc., this melatonin receptor agonist works by binding to and activating the MT1 and MT2 melatonin receptors in the brain, thereby promoting the release of melatonin and in turn, a normal circadian rhythm.2 Prior to the approval of this pharmacologic agent, melatonin was a common treatment option for blind individuals.3

Non-24-hour sleep-wake cycle syndrome is a circadian rhythm disorder in which the body’s natural 24-hour circadian rhythm or “biological clock” does not operate on a normal schedule. Those with the disorder tend to have longer than average circadian rhythms, usually lasting 25 to 26 hours and resulting in unusual sleep times and unbalanced sleep-wake patterns. Although rare in the general population (0.03% incidence rate), non-24-hour sleep-wake cycle syndrome is very common in the blind; over 50% of blind individuals live with this condition.3,4 The high incidence of this condition in the blind population is mainly attributed to the effect of sight on the synchronization of circadian rhythm. Light signals the brain to become aware of the time of day. Without light, the body’s natural clock runs with a compilation of extra minutes, eventually leading to a reverse circadian rhythm. As a result, individuals can find themselves asleep during the day and awake at night, as melatonin (normally released by the body in the evening) is released during the day, and cortisol (normally released during the day) is released at night.5 Overall, those suffering

from non-24 have difficulty falling asleep and staying awake, and possess a general feeling of grogginess and sluggishness. This disorder interferes with from non-24 have difficulty falling asleep and staying awake, and possess a general feeling of grogginess and sluggishness. This disorder interferes with daily life activities and has a negative impact on overall performance, productivity, and mood.

Tasimelteon’s effectiveness was established and evaluated in two “randomized double-masked, placebo-controlled, multicenter, parallel-group studies” in 104 totally blind individuals with non-24 hour sleep-wake cycle disorder. In Study 1 (SET), 84 patients randomly received either 20 mg tasimelteon or placebo every night for up to 6 months, while 20 participants in Study 2 (RESET, a randomized withdrawal trial that assessed maintenance) received either 20 mg tasimelteon or placebo for 3 months. Patients in the latter group then either received placebo or continued the active drug treatment, for 2 months.2 The primary endpoints were duration and timing of nighttime sleep and daytime naps, as well as entrainment rate of circadian rhythm.  Significant improvement was seen with the use of tasimelteon in comparison to placebo.6

The most commonly reported side effects include headaches, nightmares, elevated alanine aminotransferase enzymes, upper respiratory tract infections, and urinary tract infections, with a possible increased risk of adverse events in persons 65 and older. The drug has been designated Pregnancy category C. CYP1A2 and 3A4 are the major isoenzymes involved in tasimelteon metabolism, and thus its use should be avoided with strong CYP1A2 inhibitors like fluvoxamine and with strong CYP3A4 inducers like rifampin due to increased exposure/greater risk of adverse drug reactions, and decreased exposure/decreased efficacy. No dose adjustment has been deemed necessary in renal impairment or in mild or moderate hepatic impairment.2

Tasimelteon is available as a 20 mg oral capsule to be taken on an empty stomach at bedtime, at approximately the same time each night. Vanda Pharmaceuticals anticipates releasing the product to the public by the spring of this year!2



  1. Clarke T. UPDATE 2-U.S. FDA approves Vanda’s circadian rhythm drug Hetlioz. Thomson Reuters, 31 Jan. 2014. Web. 12 Feb. 2014. <UPDATE 2-U.S. FDA approves Vanda’s circadian rhythm drug Hetlioz>.
  2. Prescribing Information. Vanda Pharmaceuticals Inc, Jan. 2014. Web. 12 Feb. 2014. <http://www.hetlioz.com/Content/HetliozPI.pdf>.
  3. Non-24 hour sleep wake syndrome. American Sleep Association. N.p., Sept. 2007. Web. 12 Feb. 2014. <http://www.sleepassociation.org/index.php?p=non24hour>.
  4. Non-24 Q&A – circadian sleep disorders network. Non-24 Q&A – Circadian Sleep Disorders Network. Circadian Sleep Disorders Network, 08 Nov. 2013. Web. 14 Feb. 2014. <http://www.circadiansleepdisorders.org/docs/N24-QandA.php>.
  5. What Is Non-24?. About Non-24 A Circadian Rhythm Disorder. Vanda Pharmaceuticals Inc, Dec. 2013. Web. 12 Feb. 2014. <http://www.non-24.com/about-non-24.php>.
  6. FDA approves Hetlioz: first treatment for non-24 hour sleep-wake disorder in blind individuals. U.S. Food and Drug Administration, 31 Jan. 2014. Web. 12 Feb. 2014.<http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm384092.htm>

[pubmed_related keyword1=”tasimelteon” keyword2=”sleep” keyword3=”syndrome”]

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