Fenfluramine (Fintepla) Form

Fenfluramine (Fintepla®) is a serotonin transporter protein modulator and exhibits agonist activity at serotonin 5HT-2 receptors. FDA Approved Indication(s) Fintepla is indicated for the treatment of seizures associated with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) in patients 2 years of age and older. 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 Fintepla is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Dravet Syndrome or Lennox-Gastaut Syndrome (must meet all):

1. Diagnosis of DS or LGS;
   2. Prescribed by or in consultation with a neurologist;
   3. Age ≥ 2 years;
   4. Will be used as adjunctive therapy (see Appendix B) with at least one other antiepileptic drug;
2. 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 E); b. Both of the following (i and ii): i. For LGS, failure of two of the following, unless clinically significant adverse effects are experienced or all are contraindicated: clobazam, clonazepam, felbamate, lamotrigine, rufinamide, topiramate; ii. Failure of ≥ 3 month trial of Epidiolex® at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced;

3. Dose does not exceed any of the following (a or b): a. Members not on concomitant Diacomit® (i and ii): i. 26 mg per day; ii. 12 mL per day; b. Members on concomitant Diacomit plus clobazam (i and ii):
   i. 17 mg per day; Page 1 of 9

   CLINICAL POLICY Fenfluramine ii. 8 mL 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):

4. 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
5. 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 or Lennox-Gastaut Syndrome (must meet all):
6. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Fintepla for a covered indication and has received this medication for at least 30 days;
7. Member is responding positively to therapy;
   
   3. Fintepla will continue to be used as adjunctive therapy (see Appendix B) with at least one other antiepileptic drug;

8. If request is for a dose increase, new dose does not exceed either of the following (a or b): a. Members not on concomitant Diacomit (i and ii): i. 26 mg per day; ii. 12 mL per day; b. Members on concomitant Diacomit plus clobazam (i and ii):
   i. 17 mg per day; ii. 8 mL per day.
   Approval duration:
   Medicaid/HIM – 12 months
   Commercial – 12 months or duration of request, whichever is less Page 2 of 9

   CLINICAL POLICY Fenfluramine B. Other diagnoses/indications (must meet 1 or 2):

9. 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

10. 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.
    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 DS: Dravet syndrome FDA: Food and Drug Administration LGS: Lennox-Gastaut 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.
    Dosing Regimen Drug Name Epidiolex® (cannabidiol) topiramate (Topamax®, Qudexy® XR) Initial: 2.5 mg/kg PO BID Maintenance: 5 mg/kg PO BID LGS • Adults and Adolescents 17 years and older: Initial dose is 25 to 50 mg/day orally. Maintenance dose is 200 to 400 mg/day orally (divided and given twice daily). • Children and Adolescents 2 to 16 years: Initial dose is 1 to 3 mg/kg/day (max: 25 mg/day) Page 3 of 9 Dose Limit/ Maximum Dose 20 mg/kg/day LGS: Age ≥ 17: 400 mg/day
    Age 2 – 16: 25 mg/day DS:

    Dose Limit/ Maximum Dose 8 to 12 mg/kg/day With valproate: 100 mg/day
    With enzyme- inducing drugs: 400 mg/day
    3,600 mg/day 3,200 mg/kg/day CLINICAL POLICY Fenfluramine Drug Name Dosing Regimen lamotrigine (Lamictal® CD, ODT, XR, & Subvenite®) felbamate (Felbatol®) rufinamide (Banzel®) orally once daily in the evening. Maintenance dose is 5 to 9 mg/kg/day orally. DSǂ Initial dose is 0.5 to 2 mg/kg/day orally. Max target dose is 8 to 12 mg/kg/day orally.
    LGSǂ • Patients receiving enzyme-inducing AEDs (e.g., carbamazepine, phenobarbital, phenytoin, primidone) NOT to include valproate: o Adults and Adolescents: Initial dose is 50 mg orally daily. Maintenance dose is 300 to 500 mg/day orally given in 2 divided doses.
    o Children 2 to 12 years: Initial dose is 0.6 mg/kg/day orally in 2 divided doses. Maintenance dose is 5 to 15 mg/kg/day (max 400 mg/day) orally given in 2 divided doses. • Patients receiving valproate:
    o Adults and Adolescents: Initial dose is 25 mg orally every other day is given for 2 weeks. Maintenance dose is 100 to 400 mg/day orally, given in 1 to 2 divided doses.
    o Children 2 to 12 years: Dosage depends on weight. DSǂ Avoid lamotrigine and other sodium channel agents since they can exacerbate seizures associated with Dravet Syndrome.
    LGS Adolescents and Children 2 - 14 years: Add felbamate at 15 mg/kg/day orally in 3-4 divided doses while reducing doses of other AEDs by 20- 30%. Increase felbamate dose by 15 mg/kg/day increments at weekly intervals to 45 mg/kg/day orally. Max dose is 3,600 mg/day orally. LGS • Adults and Adolescents ≥ 17 years: Initial dose is 400-800 mg/day orally in 2 equally divided doses. Target and max dose is 3,200 mg/day orally given in 2 equally divided doses.
    • Children and Adolescents 1-16 years: Initial dose is 10 mg/kg/day orally given as 2 equally divided doses. Maintenance target dose is 45 Page 4 of 9

    Dose Limit/ Maximum Dose LGS: ≤ 30 kg: 0.2 mg/kg/day

    30 kg: 20 mg/day
    DS: 2 mg/kg/day ≤ 30 kg: 0.2 mg/kg/day 30 kg: 20 mg/day
    LGS: 60 mg/kg/day or 3,000 mg/day DS: 60 mg/kg/day CLINICAL POLICY Fenfluramine Drug Name Dosing Regimen clobazam (Onfi®) clonazepam (Klonopin®) valproic acid (Depakene®, Depakote®, Stavzor®) mg/kg/day or 3,200 mg/day orally, whichever is less, given in 2 equally divided doses. DS Avoid rufinamide and other sodium channel agents since they can exacerbate seizures associated with Dravet Syndrome.
    LGS For Adults, Adolescents, & Children older than 2 years: • Patients weighing > 30 kg: Initial dose is 5 mg orally twice daily. Max dose is 20 mg orally twice daily. Dosing should be individualized based upon efficacy and tolerability. • Patients weighing ≤ 30 kg: Initial dose is 5 mg orally once daily. Max dose is 10 mg orally twice daily. Dosing should be individualized based upon efficacy and tolerability. DSǂ Initial dose is 0.2 to 0.3 mg/kg/day PO. Max target dose is 0.5 to 2 mg/kg/day PO.
    LGS For Adults, Adolescents, & Children: • Patients weighing > 30 kg: Initial dose is 1.5 mg/day orally, given in three equally divided doses. Max dose is 20 mg/day orally, given in three equally divided doses. Patients weighing ≤ 30 kg: Initial dose is 0.01 to 0.03 mg/kg/day orally, given in three equally divided doses. Max dose is 0.1 to 0.2 mg/kg/day orally, given in three equally divided doses. LGSǂ Initial dose is 7 to 10 mg/kg/day PO, given three to four times daily for non enteric-coated capsules or syrup, BID for delayed-release tablets, and QD for the extended release preparation. A typical adult starting dose is 500 mg QD. The max dose is 60 mg/kg/day or 3,000 mg/day.
    DSǂ Initial dose is 10 to 15 mg/kg/day PO, given in two to three equally divided doses. Max target dose is 25 to 60 mg/kg/day PO, given in two to three equally divided doses, depending on achieved blood levels.
    Page 5 of 9

    CLINICAL POLICY Fenfluramine Drug Name Dosing Regimen levetiracetam (Spritam®, Keppra®) LGSǂ Initial dose is 5 mg/kg/day PO, given in two or three equal doses per day. Max dose is 20 to 80 mg/kg/day PO, according to effectiveness and tolerability.
    Dose Limit/ Maximum Dose 80 mg/kg/day DSǂ Initial dose is 10 to 20 mg/kg/day PO, divided twice daily or three times daily. Max dose is 60 to 80 mg/kg/day PO, divided twice daily or three times daily.
    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 • Contraindication(s): hypersensitivity to fenfluramine or any of the excipients in Fintepla; concomitant use, or within 14 days of the administration of monoamine oxidase inhibitors because of an increased risk of serotonin syndrome • Boxed warning(s): valvular heart disease, pulmonary arterial hypertension Appendix D: General Information • Complete seizure control is typically not achievable in DS, so the primary goal of therapy is to reduce seizure frequency. The following therapies are recommended for the management of DS by a North American consensus panel (January 2017): 1st line North American Consensus Panel Valproic acid or clobazam If first choice is not effective, then add the other 2nd line Addition of Diacomit or topiramate
    3rd line Addition of clonazepam, levetiracetam, zonisamide, ethosuximide, or phenobarbital • LGS is another severe form of epilepsy. Per American Academy of Neurology and the American Epilepsy Society Anti-Epileptic Pharmacologic Treatment Guidelines, the recommended treatment for drop seizures associated with LGS is lamotrigine and topiramate (Level A). o A Cochrane Database of Systematic Review 2013 article concluded that the optimum treatment for LGS remains uncertain and no study to date has shown any one drug to be highly efficacious; rufinamide, lamotrigine, topiramate and felbamate may be helpful as add-on therapy, and clobazam may be helpful for drop seizures. Until further research has been undertaken, clinicians will need to continue to consider each patient individually, taking into account the potential benefit of each therapy weighed against the risk of adverse effects.
    Page 6 of 9

    CLINICAL POLICY Fenfluramine Appendix E: States with Limitations against Redirections in Certain Settings State Step Therapy Notes Prohibited? No NV Applies to Medicaid requests only Failure of ONE of the following, unless all are contraindicated or clinically significant adverse effects are experienced:
    • LGS: clobazam, clonazepam, felbamate, lamotrigine, rufinamide, topiramate, Epidiolex • Dravet syndrome: Epidiolex V. Dosage and Administration
    Indication DS, LGS Dosing Regimen Initial starting and maintenance dose: 0.1 mg/kg PO BID, which can be increased weekly based on efficacy and tolerability. Maximum Dose No concomitant Diacomit: 26 mg/day Concomitant Diacomit and clobazam: 17 mg/day VI. Product Availability
    Oral solution: 2.2 mg/mL VII.