Clinical Policy: Multiple Sclerosis Drugs Reference Number: AZ.CP.PHAR.1020 Effective Date: 11.20.19 Last Review Date: 07.2020 Line of Business: Arizona Medicaid Revision Log See Important Reminder at the end of this policy for important regulatory and legal information. Description The following are multiple sclerosis drugs requiring prior authorization: dimethyl fumarate (Tecfidera®), fingolimod (Gilenya®), interferon beta-1a (Avonex®, Rebif®), interferon beta-1b (Betaseron®, Extavia®), glatiramer acetate (Copaxone®, Glatopa®), peginterferon beta-1a (Plegridy®), teriflunomide (Aubagio®), cladribine (Mavenclad®), siponimod (Mayzent®), alemtuzumab (Lemtrada®), mitoxantrone (Novantrone®), monomethyl fumarate (Bafiertam), ocrelizumab (Ocrevus®), ozanimod (Zeposia®), natalizumab (Tysabri®), and diroximel fumarate (Vumerity®). FDA Approved Indication(s) Clinically Relapsing - Secondary Primary Progressive Isolated Remitting Progressive Multiple Sclerosis Syndrome Multiple Sclerosis Multiple Sclerosis (PPMS) (CIS) (RRMS) (SPMS) Tecfidera X X X Gilenya X X X Avonex/Rebif X X X Betaseron/Extavia X X X Copaxone/Glatopa X X X Plegridy X X X Aubagio X X X Mavenclad X X Mayzent X X X Lemtrada X X Novantrone X X Bafiertam X X X Ocrevus X X X X Zeposia X X X Tysabri X X X Vumerity X X X 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 Arizona Complete Health that Tecfidera, Gilenya, Avonex, Rebif, Betaseron, Extavia, Copaxone, Glatopa, Plegridy, Aubagio, Mavenclad, Mayzent, Lemtrada, Novantrone, Bafiertam, Ocrevus, Zeposia, Tysabri, and Vumerity are medically necessary when the following criteria are met: I. Initial Approval Criteria Page 1 of 17 CLINICAL POLICY Multiple Sclerosis Drugs A. Multiple Sclerosis (must meet all): 1. Diagnosis of multiple sclerosis; 2. Prescribed by or in consultation with a neurologist; 3. For Gilenya: ALL of the following is met (a, b, and c): a) MS is classified as either CIS, RRMS, or SPMS; b) Age > 10 years; c) At the time of request, member does not have baseline QTc interval > 500 msec; 4. For Avonex or Rebif: ALL of the following is met (a, b, and c): a) MS is classified as either CIS, RRMS, or SPMS; b) Age > 2 years (for Rebif requests) or > 18 years (for Avonex requests); c) For Rebif requests for members > 18 years, failure of one of the following at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced: glatiramer (Copaxone 20 mg or Glatopa 40 mg) or Gilenya, AND Avonex; 5. For Copaxone or Glatopa: ALL of the following is met (a, b, and c): a) MS is classified as either CIS, RRMS, or SPMS; b) Age > 18 years; c) Request is for brand only: Copaxone 20 mg or Glatopa 40 mg; 6. For Betaseron or Extavia: ALL of the following is met (a, b, and c): a) MS is classified as CIS, RRMS, or SPMS; b) Age > 12 years; c) If age > 18 years, failure of one of the following at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced: glatiramer (Copaxone 20 mg or Glatopa 40 mg) or Gilenya, AND Avonex; d) For Extavia requests, failure of Betaseron at maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced; 7. For Tysabri: ALL of the following is met (a, b, and c): a) MS is classified as CIS, RRMS, or SPMS; b) Age > 18 years; c) Failure of Gilenya at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced; 8. For Tecfidera, Plegridy, Aubagio, Mayzent, Bafiertam, Zeposia, or Vumerity: ALL of the following is met (a, b, c, d, and e): a) MS is classified as CIS, RRMS, or SPMS b) Age > 18 years; c) Failure of TWO of the following at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced: Gilenya, glatiramer (Copaxone 20 mg or Glatopa 40 mg) or an interferon-beta agent (Avonex, Rebif, and Betaseron are preferred); d) For Mayzent requests, documentation that member does not have a CYP2C9*3/*3 genotype (see Appendix D); e) For Aubagio requests, member is not receiving leflunomide at time of request; 9. For Mavenclad, Lemtrada, or Novantrone: ALL of the following is met (a, b, c, and d): a) MS is classified as RRMS or SPMS (not CIS); Page 2 of 17 CLINICAL POLICY Multiple Sclerosis Drugs b) Age > 18 years; c) Failure of Gilenya AND one of the following at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced: glatiramer (Copaxone 20 mg or Glatopa 40 mg) or an interferon-beta agent (Avonex, Rebif, and Betaseron are preferred); 10. For Ocrevus: ALL of the following is met (a, b, c, and d): a) MS is classified as PPMS, CIS, RRMS, or SPMS b) Age > 18 years; c) For CIS, RRMS, or SPMS, failure of TWO of the following at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced: Gilenya, glatiramer (Copaxone 20 mg or Glatopa 40 mg), or an interferon-beta agent (Avonex, Rebif, and Betaseron are preferred); d) At the time of request, member does not have active hepatitis B infection (positive results for hepatitis B surface antigen and anti-hepatitis B virus tests); 11. Drug is not prescribed concurrently with other disease modifying therapies for MS (see Appendix D); 12. Documentation of baseline number of relapses per year and expanded disability status scale (EDSS) score (see Appendix D) ; 13. Dose does not exceed maximum dose indicated in Section V. Approval duration: 6 months (Lemtrada: 1 treatment course only, Mavenclad: up to 1 course, 2 courses lifetime total) B. Other diagnoses/indications 1. Refer to the off-label use policy for the relevant line of business if diagnosis is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized): AZ.CP.PMN.53 for Arizona Medicaid; or 2. Novantrone for diagnoses other than RRMS and SPMS: Refer to the Novantrone policy CP.PHAR.258; or 3. Tysabri for Crohn’s Disease: Refer to the AZ.CP.PHAR.06 Cytokine and CAM Antagonists policy. II. Continued Therapy A. Multiple Sclerosis (must meet all): 1. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; 2. 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, or iii): 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 (see Appendix D); iv. Medical justification supports that member is responding positively to therapy; Page 3 of 17 CLINICAL POLICY Multiple Sclerosis Drugs 3. Drug is not prescribed concurrently with other disease modifying therapies for MS (see Appendix D); 4. For Lemtrada: It has been at least 12 months since completion of the prior treatment course; 5. If request is for a dose increase, new dose does not maximum dose indicated in Section V. Approval duration: first-reauthorization: 6 months; second and subsequent reauthorizations: 12 months (Lemtrada: 1 treatment course only, Mavenclad: up to 1 course, 2 courses lifetime total) B. Other diagnoses/indications (must meet 1 or 2): 1. Currently receiving medication via Centene benefit and documentation supports positive response to therapy. Approval duration: Duration of request or 6 months (whichever is less); or 2. Refer to the off-label use policy for the relevant line of business if diagnosis is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized): AZ.CP.PMN.53 for Arizona Medicaid; or 3. Novantrone for diagnoses other than RRMS and SPMS: Refer to the Novantrone policy CP.PHAR.258; or 4. Tysabri for Crohn’s Disease: Refer to the AZ.CP.PHAR.06 Cytokine and CAM Antagonists policy. 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 – AZ.CP.PMN.53 for Arizona Medicaid or evidence of coverage documents; IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key CIS: clinically isolated syndrome FDA: Food and Drug Administration MS: multiple sclerosis PPMS: primary progressive MS RRMS: relapsing-remitting MS SPMS: secondary progressive MS EDSS: expanded disability status scale 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 Avonex®, Rebif® (interferon Avonex: 30 mcg IM Q week Avonex: 30 mcg/week beta-1a) Rebif: 22 mcg or 44 mcg SC TIW Rebif: 44 mcg TIW Betaseron® (interferon beta- 250 mcg SC QOD 250 mg QOD 1b) Page 4 of 17 CLINICAL POLICY Multiple Sclerosis Drugs Drug Name Dosing Regimen Dose Limit/ Maximum Dose glatiramer acetate 20 mg SC QD or 40 mg SC TIW 20 mg/day or 40 mg ® ® (Copaxone , Glatopa ) TIW Gilenya™ (fingolimod) 0.5 mg PO QD 0.5 mg/day Therapeutic alternatives are listed as Brand name® (generic)