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Hetlioz (tasimelteon) Prior Authorization with Quantity Limit Program Summary
Policy Number: PH-1035
This program applies to Blue Partner, Commercial, GenPlus, NetResults A series, SourceRx and Health Insurance Marketplace formularies.
POLICY REVIEW CYCLE
Effective Date |
Date of Origin |
07-01-2024 |
10-01-2014 |
FDA LABELED INDICATIONS AND DOSAGE
Agent(s) |
FDA Indication(s) |
Notes |
Ref# |
Hetlioz® (tasimelteon) Capsules* |
Treatment of Non-24-Hour Sleep-Wake Disorder (Non-24 SWD) in adults Treatment of nighttime sleep disturbances in Smith-Magenis Syndrome (SMS) in patients 16 years of age and older |
*- generic available |
1 |
Hetlioz LQ™ (tasimelteon) Oral suspension |
Treatment of nighttime sleep disturbances in Smith-Magenis Syndrome (SMS) in pediatric patients 3 to 15 years of age |
|
1 |
See package insert for FDA prescribing information: https://dailymed.nlm.nih.gov/dailymed/index.cfm
CLINICAL RATIONALE
Non-24 Hour Sleep-Wake Disorder |
Non-24 hour sleep-wake disorder (Non-24) 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 Non-24 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 hour sleep wake disorder 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 (AASM) on treatment of circadian rhythm disorders 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.(3) |
Efficacy |
The effectiveness of Hetlioz in the treatment of Non-24-Hour Sleep-Wake Disorder(Non-24) was established in two randomized double-masked, placebo-controlled, multicenter, parallel-group studies (Studies 1 and 2) in totally blind patients with Non-24. In study 1, 84 patients with Non-24 (median age 54 years) were randomized to receive Hetlioz 20 mg or placebo, one hour prior to bedtime, at the same time every night for up to 6 months. Study 2 was a randomized withdrawal trial in 20 patients with Non-24 (median age 55 years) that was designed to evaluate the maintenance of efficacy of Hetlioz after 12 weeks. Patients were treated for approximately 12 weeks with Hetlioz 20 mg one hour prior to bedtime, at the same time every night.(1) Efficacy endpoints for nighttime total sleep time and daytime nap duration were based on the 25% of nights with the least nighttime sleep, and the 25% of days with the most daytime nap time. Treatment with Hetlioz resulted in a significant improvement, compared with placebo, for both endpoints in Study 1 and Study 2.(1) |
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)
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) Hetlioz (tasimelteon) is the first FDA-approved treatment of nighttime sleep disturbance in SMS.(6) |
Efficacy |
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.(1) |
Safety |
Hetlioz and Hetlioz LQ have no FDA labeled contraindications for use.(1) |
REFERENCES
Number |
Reference |
1 |
Hetlioz prescribing information. Vanda Pharmaceuticals Inc. January 2023. |
2 |
Non-24-Hour Sleep-Wake Disorder. National Organization for Rare Disorders (NORD). Accessed January (2023. , November 20) https://rarediseases.org/rare-diseases/non-24-hour-sleep-wake-disorder/ |
3 |
Auger, R. R., Burgess, H. J., Emens, J. S., Deriy, L. V., Thomas, S. M., & Sharkey, K. M. (2015). 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. Journal of Clinical Sleep Medicine, 11(10), 1199–1236. https://doi.org/10.5664/jcsm.5100 |
4 |
Reference no longer used. |
5 |
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. |
6 |
Smith ACM, Boyd KE, Elsea SH, et. al. Smith-Magenis Syndrome. GeneReviews. October, 2022; 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 psychiatry, 32(2), 73–78. https://doi.org/10.1097/YCO.0000000000000474 |
POLICY AGENT SUMMARY PRIOR AUTHORIZATION
Target Brand Agent(s) |
Target Generic Agent(s) |
Strength |
Targeted MSC |
Available MSC |
Final Age Limit |
Preferred Status |
|
||||||
Hetlioz |
tasimelteon capsule |
20 MG |
M ; N ; O ; Y |
O ; Y |
|
|
Hetlioz lq |
tasimelteon oral susp |
4 MG/ML |
M ; N ; O ; Y |
N |
|
|
POLICY AGENT SUMMARY QUANTITY LIMIT
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
QL Amount |
Dose Form |
Day Supply |
Duration |
Addtl QL Info |
Allowed Exceptions |
Targeted NDCs When Exclusions Exist |
|
|||||||||
Hetlioz |
Tasimelteon Capsule 20 MG |
20 MG |
30 |
Capsules |
30 |
DAYS |
|
|
|
Hetlioz lq |
Tasimelteon Oral Susp |
4 MG/ML |
158 |
mLs |
30 |
DAYS |
|
|
|
CLIENT SUMMARY – PRIOR AUTHORIZATION
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
Client Formulary |
Hetlioz |
tasimelteon capsule |
20 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Hetlioz lq |
tasimelteon oral susp |
4 MG/ML |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
CLIENT SUMMARY – QUANTITY LIMITS
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
Client Formulary |
Hetlioz |
Tasimelteon Capsule 20 MG |
20 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Hetlioz lq |
Tasimelteon Oral Susp |
4 MG/ML |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL
Module |
Clinical Criteria for Approval |
|
Initial Evaluation Target Agent(s) will be approved when ALL of the following are met:
Length of Approval: 12 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.
Renewal Evaluation Target Agent(s) will be approved when ALL of the following are met:
Length of Approval: 12 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria. |
QUANTITY LIMIT CLINICAL CRITERIA FOR APPROVAL
Module |
Clinical Criteria for Approval |
|
Quantity limit for the Target Agent(s) will be approved when ONE of the following is met:
Length of Approval: up to 12 months |
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 Blue Cross and Blue Shield of Alabama’s 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.
Commercial _ PS _ Hetlioz_PAQL _ProgSum_ 07-01-2024