HETLIOZ, Tasimelteon Form

Tasimelteon (Hetlioz®, Hetlioz LQ™) is a melatonin receptor agonist. FDA Approved Indication(s) Hetlioz is indicated for treatment of:
• Non-24-hour sleep-wake disorder (non-24) in adults • Nighttime sleep disturbances in Smith-Magenis Syndrome (SMS) in patients 16 years of age and older. Hetlioz LQ is indicated for the treatment of nighttime sleep disturbances in SMS in pediatric patients 3 to 15 years of age. Tasimelteon is indicated for the treatment of Non-24-hour sleep-wake disorder (non-24) in adults.
__ Generic capsule formulation
Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Hetlioz, Hetlioz LQ, and tasimelteon are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Non-24-Hour Sleep-Wake Disorder (must meet all):

1. Diagnosis of non-24-hour sleep-wake disorder;
2. Request is for tasimelteon (Hetlioz) capsules;
3. Age ≥ 18 years;
4. Prescribed by or in consultation with a specialist in sleep disorders;
5. If request is for brand Hetlioz capsules, member must use generic tasimelteon capsules, unless contraindicated or clinically significant adverse events are experienced;
   6. Failure of melatonin and ramelteon (Rozerem®, generic is preferred), unless clinically significant adverse effects are experienced or both are contraindicated; *Prior authorization may be required for ramelteon
   7. Member has total blindness (e.g., nonfunctioning retinas);

6. Member is unable to perceive light in both eyes; Page 1 of 7

   CLINICAL POLICY Tasimelteon

   9. Dose does not exceed both of the following (a and b): a. 20 mg per day; b. 1 capsule per day. Approval duration:
      Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less B. Nighttime sleep disturbances in Smith-Magenis Syndrome (must meet all):
   10. Diagnosis of SMS confirmed by genetic testing (e.g., deletion 17p11.2 or RAI1 mutation);
   11. Request is for treatment of nighttime sleep disturbances;
7. Prescribed by or in consultation with a specialist in sleep disorders;

8. One of the following (a or b): a. Request is for tasimelteon (Hetlioz) capsules and member is ≥ 16 years old; b. Request is for Hetlioz LQ and member is 3 to 15 years of age;

   5. If request is for brand Hetlioz capsules, member must use generic tasimelteon capsules, unless contraindicated or clinically significant adverse events are experienced;
   6. Dose does not exceed one of the following (a or b): a. Tasimelteon (Hetlioz) capsules (both i and ii):
      i. 20 mg per day; ii. 1 capsule per day; b. Hetlioz LQ, one of the following (i or ii): i. Weight ≤ 28 kg: 0.7 mg per kg per day; ii. Weight > 28 kg: 20 mg per day. Approval duration:
      Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less
      C. Other diagnoses/indications (must meet 1 or 2):
   7. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
   8. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
      Page 2 of 7

   CLINICAL POLICY Tasimelteon II. Continued Therapy A. All FDA-Approved Indications (must meet all):

9. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);

   2. If request is for brand Hetlioz capsules, member must use generic tasimelteon capsules, unless contraindicated or clinically significant adverse events are experienced;
   3. Member is responding positively to therapy (e.g., increase in nighttime sleep, decrease in daytime nap time, improvement in sleep quality);
   4. If request is for a dose increase, new dose does not exceed one of the following (a or b): a. Tasimelteon (Hetlioz) capsules (both i and ii):
      i. 20 mg per day; ii. 1 capsule per day; b. Hetlioz LQ, one of the following (i or ii): i. Weight ≤ 28 kg: 0.7 mg per kg per day; ii. Weight > 28 kg: 20 mg per day. Approval duration:
      Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less
      B. Other diagnoses/indications (must meet 1 or 2):
   5. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
   6. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
      Page 3 of 7

   CLINICAL POLICY Tasimelteon III. Diagnoses/Indications for which coverage is NOT authorized:
   A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents.
   IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration SMS: Smith-Magenis Syndrome Appendix B: Therapeutic Alternatives
   This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
   Drug Name Dosing Regimen melatonin ramelteon (Rozerem) Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Non-24: 5 to 10 mg PO QHS Non-24: 8 mg PO QHS Dose Limit/ Maximum Dose N/A 8 mg/day Appendix C: Contraindications/Boxed Warnings None reported V. Dosage and Administration
   Indication Drug Name Dosing Regimen Hetlioz Hetlioz LQ Non-24-hr-sleep- wake disorder, nighttime sleep disturbances in SMS Nighttime sleep disturbances in SMS tasimelteon Non-24-hr-sleep wake disorder 20 mg PO QD one hour before bedtime, at the same time each night Weight ≤ 28 kg: 0.7 mg per kg per day PO Weight > 28 kg: 20 mg per day Dose should be given one hour before bedtime, at the same time each night 20 mg PO QD one hour before bedtime, at the same time every night VI. Product Availability
   Drug Name tasimelteon (Hetlioz) Availability Capsules: 20 mg Maximum Dose 20 mg/day See dosing regimen 20 mg/day Page 4 of 7

   CLINICAL POLICY Tasimelteon Drug Name tasimelteon (Hetlioz LQ) Availability Oral suspension: 4 mg/mL (48mL and 158 mL bottle) VII.