Tasimelteon

Medical uses

In the United States, tasimelteon capsules are indicated for the treatment of non-24-hour sleep–wake disorder (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 receptors MT1 and MT2, similar to other members of the melatonin receptor agonist class of which ramelteon (2005), melatonin (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 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 to the Food and Drug Administration 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, an advocacy group, 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.{{cite web

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".{{cite web

References

References

1. (December 2022). "Melatonin and melatonergic drugs in sleep disorders". Translational and Clinical Pharmacology.
2. (November 14, 2013). "FDA transcript approval minutes". FDA.
3. Food and Drug Administration. (January 31, 2014). "FDA approves Hetlioz: first treatment for non-24 hour sleep-wake disorder". FDA.
4. (7 July 2015). "Hetlioz Receives European Commission Approval for the Treatment of Non-24-Hour Sleep-Wake Disorder in the Totally Blind".
5. (6 July 2017). "Hetlioz EPAR".
6. "Hetlioz- tasimelteon capsule".
7. (April 2003). "Preclinical pharmacokinetics and metabolism of BMS-214778, a novel melatonin receptor agonist". Journal of Pharmaceutical Sciences.
8. (October 2000). "Entrainment of free-running circadian rhythms by melatonin in blind people". The New England Journal of Medicine.
9. {{ClinicalTrialsGov. NCT00490945. Safety and Efficacy of VEC-162 on Circadian Rhythm in Healthy Adult Volunteers
10. {{ClinicalTrialsGov. NCT00291187. VEC-162 Study in Healthy Adult Volunteers in a Model of Insomnia
11. {{ClinicalTrialsGov. NCT00548340. VEC-162 Study in Adult Patients With Primary Insomnia
12. "Improving Sleep and Alertness in the Blind (Part 5)". [[Matilda Ziegler Magazine for the Blind]].
13. (February 2009). "Melatonin agonist tasimelteon (VEC-162) for transient insomnia after sleep-time shift: two randomised controlled multicentre trials". Lancet.
14. (1 July 2015). "Outrage of the Month: FDA Makes Major Blunder After Approving Drug for Rare Sleep Disorder".
15. Food and Drug Administration. (January 31, 2014). "FDA NEWS RELEASE: FDA approves Hetlioz: first treatment for non-24 hour sleep–wake disorder in blind individuals". FDA.