Tasimelteon, sold under the brand name Hetlioz, is a medication approved by the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) in January 2014, for the treatment of

non-24-hour sleep–wake disorder Non-24-hour sleep–wake disorder (non-24, N24SWD, or N24) is one of several chronic circadian rhythm sleep disorders (CRSDs). It is defined as a "chronic steady pattern comprising ..daily delays in sleep onset and wake times in an individual ...

(also called non-24, N24 and N24HSWD). In June 2014, the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

(EMA) accepted an EU filing application for tasimelteon and in July 2015, the drug was approved in the European Union for the treatment of non-24-hour sleep-wake rhythm disorder in totally blind adults, but not in the case of non-24 in sighted people. The most common side effects include headache,

somnolence Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling aslee ...

, nausea (feeling sick) and dizziness.

Medical uses

In the United States, tasimelteon capsules are

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

for the treatment of

(Non-24) in adults and for the treatment of nighttime sleep disturbances in Smith-Magenis Syndrome (SMS) in people sixteen years of age and older. Tasimelteon oral suspension is indicated for the treatment of nighttime sleep disturbances in SMS in children from 3 to 15 years of age. In the European Union, tasimelteon capsules are indicated for the treatment of non-24-hour sleep–wake disorder (Non-24) in totally blind adults. The capsule and liquid suspension forms of tasimelteon are not interchangeable. Tasimelteon is a selective agonist for the

melatonin receptor Melatonin receptors are G protein-coupled receptors (GPCR) which bind melatonin. Three types of melatonin receptors have been cloned. The MT1 (or Mel1A or MTNR1A) and MT2 (or Mel1B or MTNR1B) receptor subtypes are present in humans and other ...

s MT₁ and MT₂, similar to other members of the melatonin receptor agonist class of which

ramelteon Ramelteon, sold under the brand name Rozerem among others, is a melatonin agonist medication which is used in the treatment of insomnia. It is indicated specifically for the treatment of insomnia characterized by difficulties with sleep onset. ...

(2005),

melatonin Melatonin, an indoleamine, is a natural compound produced by various organisms, including bacteria and eukaryotes. Its discovery in 1958 by Aaron B. Lerner and colleagues stemmed from the isolation of a substance from the pineal gland of cow ...

(2007), and agomelatine (2009) were the first approved. As a treatment for N24HSWD, as with melatonin or other melatonin derivatives, the patient may experience improved sleep timing while taking the drug. Reversion to baseline sleep performance occurs within a month of discontinuation.

Development

Tasimelteon (previously known as BMS-214,778) was developed for the treatment of

insomnia Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...

and other sleep disorders. A phase II trial on circadian rhythm sleep disorders was concluded in March 2005. A phase III insomnia trial was conducted in 2006. A second phase III trial on insomnia, this time concerning primary insomnia, was completed in June 2008. In 2010, the FDA granted orphan drug status to tasimelteon, then regarded as an investigational medication, for use in totally blind adults with N24HSWD. (Through mechanisms such as easing the approval process and extending exclusivity periods, orphan drug status encourages development of drugs for rare conditions that otherwise might lack sufficient commercial incentive.) On completion of Phase III trials, interpretations of the clinical trials by the research team concluded that the drug may have therapeutic potential for transient insomnia in circadian rhythm sleep disorders. A year-long (2011–2012) study at Harvard tested the use of tasimelteon in blind subjects with non-24-hour sleep-wake disorder. The drug has not been tested in children nor in any non-blind people.

FDA approval

In May 2013, Vanda Pharmaceuticals submitted a

New Drug Application The Food and Drug Administration's (FDA) New Drug Application (NDA) is the vehicle in the United States through which drug sponsors formally propose that the FDA approve a new pharmaceutical for sale and marketing. Some 30% or less of initial ...

to the

for tasimelteon for the treatment of non-24-hour sleep–wake disorder in totally blind people. It was approved by the FDA on January 31, 2014, under the brand name Hetlioz. In the opinion of

Public Citizen Public Citizen is an American non-profit, Progressivism in the United States, progressive consumer rights advocacy group, and think tank based in Washington, D.C. It was founded in 1971 by the American activist and lawyer Ralph Nader. Lobbying e ...

, an

advocacy group Advocacy groups, also known as lobby groups, interest groups, special interest groups, pressure groups, or public associations, use various forms of advocacy or lobbying to influence public opinion and ultimately public policy. They play an impor ...

, the FDA erroneously allowed it to be labelled without stating that it is only approved for use by totally blind people. However, FDA updated its press release on Oct. 2, 2014 to clarify the approved use of Hetlioz, which includes both sighted and blind individuals. The update did not change the drug labeling (prescribing information). In Dec 2020, tasimelteon is approved by FDA for the treatment of Smith-Magenis Syndrome.

Toxicity

Experiments with rodents revealed fertility impairments, an increase in certain cancers, and serious adverse events during pregnancy at dosages in excess of what is considered the "human dose".

References

External links