Dimethyl Fumarate (Tecfidera), Diroximel Fumarate (Vumerity), Monomethyl Fumarate (Bafiertam) Form

The following are nuclear factor-like 2 activators requiring prior authorization: dimethyl fumarate (Tecfidera®), diroximel fumarate (Vumerity®), and monomethyl fumarate (Bafiertam™). FDA Approved Indication(s) Tecfidera, Vumerity, and Bafiertam are indicated for the treatment of patients with relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. 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 Tecfidera, Vumerity, and Bafiertam are medically necessary when the following criteria are met: I. Initial Approval Criteria
A. Multiple Sclerosis (must meet all):

1. Diagnosis of one of the following (a, b, or c): a. Clinically isolated syndrome, and: i. If request is for Vumerity or Bafiertam: Member is contraindicated to both, or has experienced clinically significant adverse effects to one, of the following at up to maximally indicated doses: an interferon-beta agent (Avonex®, Betaseron®/Extavia®†, Rebif®, or Plegridy®), glatiramer (Copaxone®, Glatopa®); b. Relapsing-remitting MS, and: i. If request is for Vumerity or Bafiertam: Failure of all of the following at up to maximally indicated doses, unless clinically significant adverse effects are experienced or all are contraindicated (1, 2, 3, and 4):
   1) Dimethyl fumarate (generic Tecfidera); 2) Aubagio®; 3) Gilenya®; 4) An interferon-beta agent (Avonex, Betaseron/Extavia†, Rebif, or Plegridy) or glatiramer (Copaxone, Glatopa); Prior authorization is required for all disease modifying therapies for MS Page 1 of 7

   CLINICAL POLICY Dimethyl Fumarate, Diroximel Fumarate, Monomethyl Fumarate †Betaseron is the preferred interferon beta-1b product for the Commercial and HIM lines of business c. Secondary progressive MS;

2. Prescribed by or in consultation with a neurologist;
   3. Age ≥ 18 years;
   4. For brand Tecfidera requests, member must use generic dimethyl fumarate, unless contraindicated or clinically significant adverse effects are experienced;
3. The requested agent is not prescribed concurrently with other disease modifying therapies for MS (see Appendix D);
4. Documentation of both baseline number of relapses per year and expanded disability status scale (EDSS) score;
   7. Dose does not exceed (a and b): a. Starting dose (i and ii):
      i. Tecfidera 240 mg, Vumerity 462 mg, or Bafiertam 190 mg per day for 7 days; ii. 2 capsules per day for 7 days; b. Maintenance dose (i and ii):
      i. Tecfidera 480 mg, Vumerity 924 mg, or Bafiertam 380 mg per day; ii. Tecfidera 2 capsules, Vumerity 4 capsules, or Bafiertam 4 capsules per day. Approval duration: 6 months
      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 and HIM.PA.33 for health insurance marketplace; 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 and HIM.PA.103 for health insurance marketplace; 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 and HIM.PA.154 for health insurance marketplace. II. Continued Therapy A. Multiple Sclerosis (must meet all):

7. 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); Page 2 of 7

   CLINICAL POLICY Dimethyl Fumarate, Diroximel Fumarate, Monomethyl Fumarate

8. Member meets one of the following (a or b): a. If member has received < 1 year of total treatment: Member is responding positively to therapy; b. If member has received ≥ 1 year of total treatment: Member meets one of the following (i, ii, iii, or iv): i. Member has not had an increase in the number of relapses per year compared to baseline; ii. Member has not had ≥ 2 new MRI-detected lesions; iii. Member has not had an increase in EDSS score from baseline; iv. Medical justification supports that member is responding positively to therapy;
9. For brand Tecfidera requests, member must use generic dimethyl fumarate, unless contraindicated or clinically significant adverse effects are experienced;
10. The requested agent is not prescribed concurrently with other disease modifying therapies for MS (see Appendix D);
11. If request is for a dose increase, new dose does not exceed (a and b): a. Tecfidera 480 mg, Vumerity 924 mg, or Bafiertam 380 mg per day; b. Tecfidera 2 capsules, Vumerity 4 capsules, or Bafiertam 4 capsules per day. Approval duration:
    If member has received < 1 year of total treatment – up to a total of 12 months of treatment If member has received ≥ 1 year of total treatment – 12 months B. Other diagnoses/indications (must meet 1 or 2):
12. 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 and HIM.PA.33 for health insurance marketplace; 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 and HIM.PA.103 for health insurance marketplace; or

13. 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 and HIM.PA.154 for health insurance marketplace. 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 and HIM.PA.154 for health insurance marketplace or evidence of coverage documents; B. Primary progressive MS. Page 3 of 7

    CLINICAL POLICY Dimethyl Fumarate, Diroximel Fumarate, Monomethyl Fumarate IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key EDSS: expanded disability status scale
    FDA: Food and Drug Administration MS: multiple sclerosis 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 14 mg/day Avonex: 30 mcg/week Rebif: 44 mcg TIW 250 mg QOD 7 mg or 14 mg PO QD Avonex: 30 mcg IM Q week Rebif: 22 mcg or 44 mcg SC TIW 250 mcg SC QOD Aubagio® (teriflunomide) Avonex®, Rebif® (interferon beta-1a) Betaseron®, Extavia® (interferon beta-1b) Plegridy® (peginterferon beta-1a) glatiramer acetate (Copaxone®, Glatopa®) Gilenya® (fingolimod) 0.5 mg PO QD 120 mg PO BID for 7 days, dimethyl fumarate (Tecfidera®) followed by 240 mg PO BID 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. 20 mg/day or 40 mg TIW 0.5 mg/day 480 mg/day 20 mg SC QD or 40 mg SC TIW 125 mcg SC Q2 weeks 125 mcg/2 weeks Appendix C: Contraindications/Boxed Warnings • Contraindication(s): known hypersensitivity to dimethyl fumarate, diroximel fumarate, or any of the excipients of Tecfidera, Vumerity, or Bafiertam; coadministration of Tecfidera, Vumerity, and Bafiertam • Boxed warning(s): none reported Appendix D: General Information • Disease-modifying therapies for MS are: glatiramer acetate (Copaxone®, Glatopa®), interferon beta-1a (Avonex®, Rebif®), interferon beta-1b (Betaseron®, Extavia®), peginterferon beta-1a (Plegridy®), dimethyl fumarate (Tecfidera®), diroximel fumarate (Vumerity®), monomethyl fumarate (Bafiertam™), fingolimod (Gilenya®, Tascenso ODT™), teriflunomide (Aubagio®), alemtuzumab (Lemtrada®), mitoxantrone (Novantrone®), natalizumab (Tysabri®), ocrelizumab (Ocrevus®), cladribine (Mavenclad®), siponimod (Mayzent®), ozanimod (Zeposia®), ponesimod (Ponvory™), ublituximab-xiiy (Briumvi™), and ofatumumab (Kesimpta®). • Of the disease-modifying therapies for MS that are FDA-labeled for CIS, only the interferon products, glatiramer, and Aubagio have demonstrated any efficacy in Page 4 of 7

    CLINICAL POLICY Dimethyl Fumarate, Diroximel Fumarate, Monomethyl Fumarate decreasing the risk of conversion to MS compared to placebo. This is supported by the American Academy of Neurology 2018 MS guidelines. • Tecfidera and Vumerity are both prodrugs of Bafiertam. V. Dosage and Administration
    Drug Name Dimethyl fumarate (Tecfidera) Diroximel fumarate (Vumerity) Monomethyl fumarate (Bafiertam) Dosing Regimen Starting: 120 mg PO BID for 7 days Maintenance: 240 mg PO BID Starting: 231 mg PO BID for 7 days Maintenance: 462 mg PO BID Starting: 95 mg PO BID for 7 days Maintenance: 190 mg PO BID Maximum Dose 480 mg/day 924 mg/day 380 mg/day VI. Product Availability Availability Drug Name Delayed-release capsules: 120 mg, 240 mg Dimethyl fumarate (Tecfidera) Diroximel fumarate (Vumerity) Delayed-release capsule: 231 mg Monomethyl fumarate (Bafiertam) Delayed-release capsule: 95 mg VII.