LEMTRADA, Alemtuzumab (MS) Form

Alemtuzumab (Lemtrada®) is a CD52-directed cytolytic monoclonal antibody. FDA Approved Indication(s) Lemtrada is indicated for the treatment with relapsing forms of multiple sclerosis (MS), to include relapsing-remitting disease and active secondary progressive disease, in adults. Because of its safety profile, the use of Lemtrada should generally be reserved for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS. Limitation(s) of use: Lemtrada is not recommended for use in patients with clinically isolated syndrome (CIS) because of its safety profile. 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 Lemtrada is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Multiple Sclerosis (must meet all):

1. Diagnosis of relapsing-remitting or secondary progressive MS;
   2. Prescribed by or in consultation with a neurologist;
   3. Age ≥ 18 years;
   4. Failure of all of the following at up to maximally indicated doses, unless clinically significant adverse effects are experienced or all are contraindicated (a, b, c, and d):
      a. Dimethyl fumarate (generic Tecfidera®);
      b. Teriflunomide (generic Aubagio®);
      c. Fingolimod (Gilenya®); d. An interferon-beta agent (Avonex®, Betaseron®/Extavia®†, Rebif®, or Plegridy®) or glatiramer (Copaxone®, Glatopa®); Prior authorization may be required for all disease modifying therapies for MS †Betaseron is preferred for the Commercial and HIM lines of business; Extavia is preferred for the Medicaid line of business
2. Lemtrada is not prescribed concurrently with other disease modifying therapies for MS (see Appendix D);

3. Documentation of both baseline number of relapses per year and expanded disability status scale (EDSS) score; Page 1 of 7

   CLINICAL POLICY Alemtuzumab

4. Dose does not exceed: a. First treatment course: 12 mg per day for 5 consecutive days (60 mg total); b. Second or subsequent treatment courses: 12 mg per day for 3 consecutive days (36 mg total). Approval duration:
   Medicaid/HIM – 12 months (1 treatment course only) Commercial – 6 months or to the member’s renewal date, whichever is longer (1 treatment course only) 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.
   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);
8. Member is responding positively to therapy as evidenced by one of the following (a, b, c, or d): a. Member has not had an increase in the number of relapses per year compared to baseline; b. Member has not had ≥ 2 new MRI-detected lesions; c. Member has not had an increase in EDSS score from baseline; d. Medical justification supports that member is responding positively to therapy;
   3. Lemtrada is not prescribed concurrently with other disease modifying therapies for MS (see Appendix D);

9. It has been at least 12 months since completion of the prior treatment course; Page 2 of 7

   CLINICAL POLICY Alemtuzumab

10. Dose does not exceed 12 mg per day for 3 consecutive days (36 mg total per treatment course). Approval duration:
    Medicaid/HIM – 12 months (1 treatment course only) Commercial – 6 months or to the member’s renewal date, whichever is longer (1 treatment course only) B. Other diagnoses/indications (must meet 1 or 2):
11. 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

12. 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 policy – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid or evidence of coverage documents; B. Primary progressive MS. 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 teriflunomide (Aubagio®) 7 mg or 14 mg PO QD Page 3 of 7

    CLINICAL POLICY Alemtuzumab Drug Name Dosing Regimen Dose Limit/ Maximum Dose Avonex: 30 mcg/week Rebif: 44 mcg TIW 125 mcg/2 weeks 250 mcg SC QOD Avonex: 30 mcg IM Q week Rebif: 22 mcg or 44 mcg SC TIW 125 mcg SC Q2 weeks Avonex®, Rebif® (interferon beta-1a) Plegridy® (peginterferon beta-1a) Betaseron®, Extavia® (interferon beta-1b) glatiramer acetate (Copaxone®, Glatopa®) fingolimod (Gilenya®) 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 250 mg QOD Appendix C: Contraindications/Boxed Warnings • Contraindication(s): hypersensitivity or anaphylactic reactions to alemtuzumab or any of the excipients in Lemtrada, infection with human immunodeficiency virus, active infection • Boxed warning(s): autoimmunity, infusion reactions, stroke, and malignancies 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®). • Lemtrada is available only through a restricted program under a REMS called the Lemtrada REMS Program because of the risks of autoimmunity, infusion reactions, and malignancies. V. Dosage and Administration
    Indication Relapsing MS Dosing Regimen IV infusion for 2 or more treatment courses:
    • First course: 12 mg/day on 5 consecutive days • Second course: 12 mg/day on 3 consecutive days 12 months after first course • Subsequent courses as needed: 12 mg/day on 3 consecutive days 12 months after any prior course Maximum Dose See regimen VI. Product Availability
    Single-use vial: 12 mg/1.2 mL Page 4 of 7

    CLINICAL POLICY Alemtuzumab VII.