Drugs in Perspective: Tasimelteon (Hetlioz)

Introduction

It is estimated that up to 100,000 people in the United States have non-24-hour-sleep-wake disorder (N24HSWS). It shares symptoms that are similar to other sleep disorders the criteria for the presence of this disorder is a complain of cyclic insomnia and/or excessive daytime sleepiness^.1 This abnormality is suggested to be related to the lack of synchronicity between the 24-hour day-night cycle and the body’s internal clock.1 Individuals who are thought to have this disorder do not have internal clocks that can reset and remain in homeostasis within a 24-hour schedule so in certain situations they can have longer circadian rhythms. ² Aside from the fact that the condition can cause stress and depression it considered not to be harmful as the quality of deep sleep is equal to those without the disorder.² Melatonin is considered to be most commonly utilized treatment for the disorder along with light treatment or acupuncture. Hetlioz (tasimelteon) is a melatonin receptor agonist, similar to Rozerem (ramelteon) that was approved by FDA in January 2014 for the treatment of N24HSWS caused by a completely blind person’s inability to regulate their internal clock.³  Hetlioz is available in 20-mg capsules and should be administered as 1 capsule prior to bedtime with food. It works optimally when administered at the same time daily. The drug is produced by Vanda Pharmaceutucals based in Washington, D.C.^3,4

See February 2014 FDA drug approvals.

FDA recommends a lower starting dose for Lunesta

Relevance

Hetlioz is the second drug in the class of melatonin receptor agonist to be released, following Rozerem but unlike Rozerem which has a labeled indication for insomnia characterized by difficulty with sleep onset, Hetlioz is specifically indicated for N24HSWS which is the first approved treatment.^3,5  This indication was established in totally blind patients with the disorder.

There are currently no published trials of Hetlioz for the treatment of N24HSWS. However, the results of 2 studies were presented at the 95^th Annual Meeting and Expo of The Endocrine Society in 2013.  These studies include the SET study (n=84) and the RESET study (n=20).

It is also worthy of note that there have been no clinical research trials that compare the use of Hetlioz and melatonin in a head-to-head fashion. FDA approved Hetlioz based on placebo-controlled trials. Its effectiveness has not to this point been directly compared to taking over-the-counter melatonin, which has previously been the standard of care for this condition. Timed melatonin administration is a “guideline” recommendation by the American Academy of Sleep Medicine and reflects a moderate degree of clinical certainty based on five cohort studies and clinical trials.

Click to enlarge

Studies

The safety and efficacy of Hetlioz was established through a clinical study that consisted of 104 completely blind participants. The blind participants with the disorder experienced significant improvement in their nighttime sleep with treated with Hetlioz compared to placebo^.5,6 They also experienced decreased daytime sleep. The reported side effects of some patients included headache, upper respiratory and urinary tract infections, or unusual dreams.^5,6

Potential advantages
and disadvantages

Hetlioz is recognized as the first FDA approved drug to treat N24HSWS in blind patients which offers a new treatment approach for those who have long suffered from this condition but a risk versus benefit assessment must be performed prior to initiation due to its potential side effect profile and potential to negatively impact mental alertness.⁶

Cost

The cost of Hertlioz has been established at $281 (AWP) per capsule or $102,000 per patient per year.⁷

Place in Therapy

Hetlioz is the first melatonin receptor agonist to be indicated for the treatment of N24HSWS in blind patients which makes it novel in its indication, as well as serving as the first FDA approved drug to treat this unique sleep disorder^.6,7

Implications

The FDA approval of Hetlioz has significant implications on the treatment of N24HSWS in blind patients since there has been no other drug that has been indicated in this particular population. Due to its high cost, this medication will be managed by most payers as a specialty drug, and will be subjected to utilization management controls like prior authorization and quantity limits to ensure appropriate, cost-efficient usage.⁸

Its approval allows for many individuals who have long suffered from this disorder to finally be treated appropriately and effectively. The sleep patterns of many blind patients with this disorder can be potentially repaired with a trial of Hetlioz.

Dr Farinde serves on the faculty at Columbia Southern University, Orange Beach, Ala.

Disclosure information: The author reports no financial disclosures as related to products discussed in this article.

References

National Sleep Foundation. Non-24-hour sleep wake disorder: Symptoms and diagnosis. Available at http://sleepfoundation.org/non-24/symptoms.html. Accessed August 5, 2014.

American Sleep Association. Non-24 hour sleep wake syndrome.  Available at http://www.sleepassociation.org/index.php?p=non24hour. Accessed August 5, 2014.

Hetlioz (Tasimelteon) Lexi-Comp Online, Lexicomp. Hudson, Ohio: Lexi-Comp, Inc.; March 3, 2014.

HealthDay. Hetlioz approved for sleep disorder in blind people. Available at http://www.medicinenet.com/script/main/art.asp?articlekey=176503. Accessed August 5, 2014.

Prior A. FDA Approves Hetlioz for sleep disorder in fully-blind patients.The Wall Street Journal. Available at http://online.wsj.com/news/articles/SB1000142405270230397370457935510200507171. Accessed August 5, 2014.

Root C. The FDA has approved Hetlioz for sleep-wake disorder. Bioresearch Online. 2014. Available at http://www.bioresearchonline.com/doc/the-fda-has-approved-hetlioz-for-sleep-wake-disorder-0001. Accessed August 5, 2014.

Medispan. Heliotz. Retrieved from http://www.medispan.com/  Accessed July 3, 2014.

Hetlioz^TM [package insert]. Washington D.C.: Vanda Pharmaceuticals;January 2014.