ph-991035
print Print Back Back

Hetlioz (tasimelteon) Prior Authoriztaion with Quantity Limit Program Summary

Policy Number: PH-991035

This program is implemented on the Blue Partner, Commercial, GenPlus, NetResults A series, SourceRx and Health Insurance Marketplace formularies.

Hetlioz (tasimelteon) Prior Authorization with Quantity Limit

TARGET AGENT(S)

Hetlioz® (tasimelteon)

Hetlioz LQ (tasimelteon)

Brand (generic)

GPI

Multisource Code

Quantity Limit (per day or as listed)

Hetlioz (tasimelteon)

20 mg capsule

60250070000130

M, N, O, or Y

1 capsule

Hetlioz LQ (tasimelteon)

4 mg/mL oral suspension

60250070001820

M, N, O, or Y

158 mLs

PRIOR AUTHORIZATION AND QUANTITY LIMIT CRITERIA FOR APPROVAL

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met: 

  1. ONE of the following:
    1. BOTH of the following:
      1. The patient has a diagnosis of Non-24-hour sleep-wake disorder

AND

      1. The patient is totally blind (i.e., no light perception)

OR

    1. BOTH of the following:
      1. The patient has a diagnosis of Smith-Magenis Syndrome (SMS) confirmed by the presence of ONE of the following genetic mutations:
        1. A heterozygous deletion of 17p11.2

OR

        1. A heterozygous pathogenic variant involving RAI1

AND

      1. The requested agent is being used to treat nighttime sleep disturbances associated with SMS

OR

    1. The patient has another FDA approved indication for the requested agent

AND

  1. ONE of the following:
    1. The patient’s age is within FDA labeling for the requested indication for the requested agent

OR

    1. The prescriber has provided information in support of using the requested agent for the patient’s age

AND

  1. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., sleep specialist, neurologist, psychiatrist) or has consulted with a specialist in the area of the patient’s diagnosis

AND

  1. The patient does NOT have any FDA labeled contraindications to the requested agent

AND

  1. ONE of the following:
    1. The requested quantity (dose) does NOT exceed the program quantity limit

OR

    1. ALL of the following:
      1. The requested quantity (dose) is greater than the program quantity limit

AND

      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication

AND

      1. The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does not exceed the program quantity limit

OR

    1. ALL of the following:
      1. The requested quantity (dose) is greater than the program quantity limit

AND

      1. The requested quantity (dose) is greater than the maximum FDA labeled dose for the requested indication

AND

      1. The prescriber has submitted documentation in support of therapy with a higher dose for the requested indication

Length of Approval:  12 months

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met: 

  1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process

AND

  1. The patient has had clinical benefit with the requested agent

AND

  1. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., sleep specialist, neurologist, psychiatrist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis

AND

  1. The patient does NOT have any FDA labeled contraindications to the requested agent

AND

  1. ONE of the following:
    1. The requested quantity (dose) does NOT exceed the program quantity limit

OR

    1. ALL of the following:
      1. The requested quantity (dose) is greater than the program quantity limit

AND

      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication

AND

      1. The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does not exceed the program quantity limit

OR

    1. ALL of the following:
      1. The requested quantity (dose) is greater than the program quantity limit

AND

      1. The requested quantity (dose) is greater than the maximum FDA labeled dose for the requested indication

AND

      1. The prescriber has submitted documentation in support of therapy with a higher dose for the requested indication

Length of Approval: 12 months

FDA APPROVED INDICATIONS AND DOSAGE1

Agent(s)

Indication(s)

Dosage

Hetlioz®, Hetlioz LQ

(tasimelteon)

Capsule

Oral suspension

Treatment of Non-24-Hour Sleep-Wake Disorder (Non-24) in adults

20 mg prior to bedtime, at same time every night

Take without food

Treatment of nighttime sleep disturbances in Smith-Magenis Syndrome (SMS) in patients 16 years of age and older for the capsules and 3 years to 15 years for the oral solution

16 years and older: 20 mg capsule prior to bedtime, at the same time every night

3 to 15 years old: oral suspension dose based on weight prior to bedtime, at the same time every night

  • ≤28 kg: 0.7 mg/kg
  • >28 kg: 20 mg

CLINICAL RATIONALE

Non-24 Hour Sleep-Wake Disorder

Non-24 hour sleep-wake disorder (N24) is a circadian rhythm sleep disorder that is due to the failure of the biological clock to synchronize to a 24-hour day.2 Numerous biological processes require an endogenous, entrainable oscillation with a period of about 24 hours, also known as the circadian rhythm. Retinal rods, cones, and ganglion cells that express the photopigment melanopsin play a key role in circadian photoentrainment. Light that reaches the photoreceptors activates the suprachiasmatic nuclei (SCN), which contains the master biological clock, activating a regulatory feedback loop that inhibits melatonin synthesis. In totally blind patients, the circadian process can become desynchronized due to the absence of light input into the master biological clock.5 

Patients with N24 typically find their sleep time gradually delaying by minutes to hours every day, rather than sleeping at roughly the same time every day. Cycles of body temperature and hormone rhythms also follow a non-24 hour rhythm.

If Non-24 is not detected and addressed, and the person attempts to stay on a 24-hour schedule, the symptoms of chronic sleep deprivation will accumulate, such as excessive daytime sleepiness, fatigue, depression, difficulty concentrating, and memory problems.  Non-24 can be severely disabling as it causes extreme difficulty for the individual attempting to maintain social and career obligations.2 The condition primarily occurs in blind individuals, and at least 50% of the totally blind (i.e., those with no light perception) are thought to suffer from the disorder.3  

The American Academy of Sleep Medicine guidelines on treatment of circadian rhythm disorders (AASM, 2015) recommends clinicians use strategically timed administration of melatonin for treatment of Non-24-Hour Sleep-Wake Disorder in blind adults (vs. no treatment).  The suggestion carried a Weak recommendation, as there were only 3 studies that met the task force’s inclusion criteria for analysis, and the level of evidence from these small trials was low.  The task force states that no serious adverse reactions to melatonin have been described to date and therefore benefits of use appear to outweigh any potential harm.4

Efficacy

Tasimelteon is a melatonin receptor agonist indicated for the treatment of Non-24-Hour-Sleep-Wake Disorder.  In the Safety and Efficacy of Tasimelteon (SET) trial, 84 totally blind patients were randomized to 20mg of tasimelteon or placebo.  Patients assigned to the tasimelteon were more likely to be entrained at one month (20% versus 3%).  Entrainment rates improved to 50% in individuals assessed at 6 weeks.4 

Smith-Magenis Syndrome (SMS)

Smith-Magenis Syndrome (SMS) is genetic condition resulting in developmental delays, cognitive impairment, behavioral abnormalities, sleep disturbances, distinctive physical features, and childhood abdominal obesity. SMS is a result of a deletion of the retinoic acid induced 1 (RAI1) gene in chromosome 17p11.2. Most cases are the result of de novo deletions, but rare occurrences of inherited cases have occurred.7

The diagnosis of SMS is established via a combination of clinical features and genetic testing. Clinical features suspect of SMS include the following:6

  • Subtly distinctive facial appearance that becomes more evident with age
  • Mild to moderate infantile hypotonia with feeding difficulties and failure to thrive
  • Peripheral neuropathy
  • Some level of developmental delay and/or intellectual disability, including early speech delays with or without associated hearing loss
  • Distinct neurobehavioral phenotype that includes stereotypic and maladaptive behaviors and sleep disturbance
  • Short stature (prepubertal)
  • Minor skeletal anomalies, including brachydactyly
  • Ophthalmologic abnormalities
  • Otolaryngologic abnormalities

The presence of either a heterozygous deletion at chromosome 17p11.2 that includes RAI1 or a heterozygous intragenic RAI1 pathogenic variant are definitive of a SMS diagnosis.6

Sleep disturbances are a major clinical characteristic of SMS. The sleep disturbances are believed to be attributed to a primary disturbance of the circadian clock, with RAI1 functioning as a positive regulator of the Circadian Locomotor Output Cycles Kaput (CLOCK) gene transcription. The dysregulation of CLOCK results in dysregulation of other circadian clock components. Patients with SMS also have elevated levels of daytime melatonin resulting in daytime sleepiness. The sleep disturbances manifest as fragmented sleep cycles with a reduction in total sleep time. Patients may complain of frequent nighttime awakenings, parasomnias, and excessive daytime sleepiness.7

Sleep disturbances contribute to behavioral problems typical to SMS, and normalizing sleep habits, improved both behavior and quality of life for patients and families. There is currently no pharmaceutical standard of care, but melatonin has been used in case reports with some response.6,7

Efficacy1

The effectiveness of Hetlioz in the treatment of nighttime sleep disturbances in Smith-Magenis Syndrome (SMS) was established in a 9-week, double-blind, placebo-controlled crossover study in adults and pediatric patients with SMS (Study 3; NCT 02231008). Patients 16 years of age and older received Hetlioz 20 mg capsules, and pediatric patients 3 years to 15 years of age received a weight-based dose of oral suspension. The efficacy comparisons for nighttime sleep quality and total sleep time were based on the 50% of nights with the worst sleep quality and the 50% of nights with the least nighttime sleep in each 4-week period. In accordance with the cross-over design, the efficacy comparisons were within patient. Compared to placebo, treatment with Hetlioz resulted in a statistically significant improvement in the 50% worst nights’ sleep quality.

REFERENCES

  1. Hetlioz prescribing information. Vanda Pharmaceuticals Inc. December 2020.
  2. Non-24-Hour Sleep-Wake Disorder.  National Organization for Rare Disorders (NORD).  Accessed November 2020.  https://rarediseases.org/rare-diseases/non-24-hour-sleep-wake-disorder/
  3. Auger RR, Burgess HJ, Emens JS, et. al.  Clinical Practice Guideline for the Treatment of Intrinsic Circadian Rhythm Sleep-Wake Disorders:  Advanced Sleep-Wake Phase Disorder (ASWPD), Delayed Sleep-Wake Phase Disorder (DSWPD), Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD), and Irregular Sleep-Wake Rhythm Disorder (ISWRD).  An Update for 2015.  Accessed November 2020.  http://jcsm.aasm.org/ViewAbstract.aspx?pid=30219
  4. Quera Salva Maria Antonia, Hartley Sarah, Léger Damien, Dauvilliers Yves A. (2017) Non-24-Hour Sleep–Wake Rhythm Disorder in the Totally Blind: Diagnosis and Management. Frontiers in Neurology, 8(686), pages 1-7. Doi: 10.3389/fneur.2017.00686.
  5. Lockley SW, Dressman MA, et al.  Tasimelteon for non-24-hour sleep-wake disorder in totally blind people (SET and RESET): two multicenter, randomized, double-masked, placebo-controlled phase 3 trials.  The Lancet, October 31, 2015, 386:10005 1754-1764. 
  6. Smith ACM, Boyd KE, Elsea SH, et. al. Smith-Magenis Syndrome. GeneReviews. June 28, 2012; https://www.ncbi.nlm.nih.gov/books/NBK1310/.
  7. Shayota, B. J., & Elsea, S. H. (2019). Behavior and sleep disturbance in Smith-Magenis syndrome. Current opinion in psychiatry32(2), 73–78. https://doi.org/10.1097/YCO.0000000000000474

This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.
 
The purpose of pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.
 
Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.

ALBP_PS_Hetlioz_PAQL_ProgSum_AR0321