Cenobamate (Xcopri) Form

Cenobamate (Xcopri®) is a voltage-gated sodium channel inhibitor and a positive allosteric modulator of the γ-aminobutyric acid (GABAA) ion channel. FDA Approved Indication(s) Xcopri is indicated for the treatment of partial-onset seizures in adult patients. 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 Xcopri is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Partial-Onset Seizures (must meet all):

1. Diagnosis of partial-onset seizures;
2. Prescribed by or in consultation with a neurologist;
3. Age ≥ 18 years;

4. Member meets one of the following (a or b): a. Request is for the treatment of a member in a State with limitations on step therapy in certain settings (see Appendix D); b. Failure of two preferred anticonvulsants indicated for partial seizures (see Appendix B for examples), unless clinically significant adverse effects are experienced or all are contraindicated;

   5. Dose does not exceed both of the following (a and b):
      a. 400 mg per day;
      b. 2 tablets 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):
   6. 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): Page 1 of 6

   CLINICAL POLICY Cenobamate 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

   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. Partial-Onset Seizures (must meet all):
   3. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Xcopri for a covered indication and has received this medication for at least 30 days;
   4. Member is responding positively to therapy;

5. If request is for a dose increase, new dose does not exceed both of the following (a or b):
   a. 400 mg per day;
   b. 2 tablets 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: 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.
      Page 2 of 6

   CLINICAL POLICY Cenobamate 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 GABAA: γ-aminobutyric acid-subtype A 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 Dose Limit/ Maximum Dose Refer to prescribing information Refer to prescribing information carbamazepine (Carbatrol®, Epitol®, Equetro®, Tegretol®, Tegretol XR®) felbamate (Felbatol®) gabapentin (Neurontin®) lamotrigine (Lamictal®, Lamictal CD®, Lamictal ODT®, Lamictal XR®) levetiracetam (Elepsia XR®, Keppra®, Keppra XR®, Roweepra®, Spritam®) oxcarbazepine (Oxtellar XR®, Trileptal®) phenobarbital (Luminal®) phenytoin (Dilantin®, Phenytek®) pregabalin (Lyrica®, Lyrica® CR) tiagabine (Gabitril®) topiramate (Qudexy XR®, Topamax®, Topamax Sprinkle®, Topiragen®, Trokendi XR®) valproic acid, divalproex sodium (Depakene®, Depakote Sprinkle®, Depakote ER®, Depakote®) zonisamide (Zonegran®) 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. Appendix C: Contraindications/Boxed Warnings • Contraindication(s): hypersensitivity to cenobamate or any of the inactive ingredients in Xcopri; familial short QT syndrome • Boxed warning(s): none reported Page 3 of 6

   CLINICAL POLICY Cenobamate Appendix D: States with Limitations against Redirections in Certain Settings State Step Therapy Notes Prohibited? No NV Applies to Medicaid requests only Failure of ONE preferred anticonvulsant indicated for partial seizures (see Appendix B for examples), unless all are contraindicated or clinically significant adverse effects are experienced. V. Dosage and Administration
   Indication Partial-onset seizures Dosing Regimen Dose titration: 12.5 mg PO QD for two weeks, then 25 mg PO QD for two weeks, then 50 mg PO QD for two weeks, then 100 mg PO QD for two weeks, then 150 mg PO QD for two weeks Maximum Dose 400 mg/day Maintenance dose: 200 mg PO QD If needed based on clinical response and tolerability, dose may be increased above 200 mg by increments of 50 mg PO QD every two weeks to 400 mg PO QD. VI. Product Availability
   Tablets: 12.5 mg, 25 mg, 50 mg, 100 mg, 150 mg, 200 mg VII.