DIACOMIT, Stiripentol Form

Stiripentol (Diacomit®) is an anticonvulsant. FDA Approved Indication(s) Diacomit is indicated for the treatment of seizures associated with Dravet syndrome in patients taking clobazam who are 6 months of age and older and weighing 7 kg or more. There are no clinical data to support the use of Diacomit as monotherapy in Dravet syndrome.
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 Diacomit is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Dravet Syndrome (must meet all):

1. Diagnosis of Dravet syndrome;
2. Prescribed by or in consultation with a neurologist;
3. Age ≥ 6 months;
4. Member weighs ≥ 7 kg;
5. Will be used as adjunctive therapy (see Appendix B) with at least one other antiepileptic drug;
   6. Failure of ≥ 3 month trial of Epidiolex® at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced;

6. Dose does not exceed 50 mg/kg (up to a maximum of 3,000 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):

   1. 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: Page 1 of 6

   CLINICAL POLICY Stiripentol 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

   2. 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.
      II. Continued Therapy A. Dravet Syndrome (must meet all):
   3. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Diacomit for Dravet syndrome and has received this medication for at least 30 days;
   4. Member is responding positively to therapy;

7. Diacomit will continue to be used as adjunctive therapy (see Appendix B) with at least one other antiepileptic drug;

   4. If request is for a dose increase, new dose does not exceed 50 mg/kg (up to a maximum of 3,000 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.
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   CLINICAL POLICY Stiripentol 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 EEG: electroencephalography MRI: magnetic resonance imaging NICE: National Institute for Health and Care Excellence 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 Initial: 0.2-0.3 mg/kg/day PO Initial: 10-15 mg/kg/day PO, given in 2-3 equally divided doses
   Initial: 0.5-2 mg/kg/day PO Initial: 10-20 mg/kg/day PO, divided in 2-3 doses PO; off-label dosing information not available Dose Limit/ Maximum Dose 0.5-2 mg/kg/day
   25-60 mg/kg/day 8-12 mg/kg/day 60-80 mg/kg/day Off-label dosing information not available clobazam (Onfi® , Sympazan®) valproic acid (Depakene®, Depakote®, Stavzor®) topiramate (Topamax®, Trokendi® XR, Qudexy® XR) levetiracetam (Spritam®, Keppra®) Other antiepileptic drugs: clonazepam (Klonopin®), zonisamide (Zonegran®), ethosuximide (Zarontin®), phenobarbital Epidiolex® (cannabidiol) Initial: 2.5 mg/kg PO BID Maintenance: 5 mg/kg PO BID
   20 mg/kg/day
   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. *Off-label Appendix C: Contraindications/Boxed Warnings None reported
   Appendix D: General Information • Dravet syndrome, also known as severe myoclonic epilepsy of infancy (SMEI), is a severe form of epilepsy with an incidence of 1 in 15,700 to 1 in 40,900. Diagnosis is largely based on clinical presentation as magnetic resonance imaging (MRI) is usually normal and electroencephalography (EEG) findings are nonspecific.
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   CLINICAL POLICY Stiripentol • Complete seizure control is typically not achievable, so the primary goal of therapy is to reduce seizure frequency. The following therapies are recommended for the management of Dravet syndrome by the United Kingdom National Institute for Health and Care Excellence (NICE; April 2018) and a North American Consensus Panel (January 2017): 1st line NICE Valproic acid or topiramate 2nd line Addition of clobazam or 3rd line Diacomit Refer to tertiary specialist
   North American Consensus Panel Valproic acid or clobazam If first choice is not effective, then add the other Addition of Diacomit or topiramate
   Addition of clonazepam, levetiracetam, zonisamide, ethosuximide, or phenobarbital • Diacomit increases plasma concentrations of clobazam through inhibition of CYP3A4 and 2C19.
   • FDA-approved in August 2018, Diacomit had long prior been used in clinical practice in Canada, Japan, and European countries as well as off-label in the United States through a compassionate-use program. V. Dosage and Administration
   Indication Dravet syndrome Dosing Regimen Age ≥ 6 months and weighing 7 kg to < 10 kg: 25 mg/kg twice daily Age ≥ 1 year and weighing ≥ 10 kg: 25 mg/kg twice daily or 16.67 mg/kg three times daily Maximum Dose 50 mg/kg/day (not to exceed 3,000 mg/day) VI. Product Availability
   • Capsules: 250 mg, 500 mg
   • Powder for oral suspension: 250 mg, 500 mg
   VII.