MAVENCLAD, Cladribine (Multiple Sclerosis) Form

Cladribine (Mavenclad®) is a cytotoxic purine antimetabolite. FDA Approved Indication(s) Mavenclad is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include relapsing-remitting disease and active secondary progressive disease, in adults.
Because of its safety profile, use of Mavenclad is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS. Limitation(s) of use: Mavenclad 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 Mavenclad is 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 or b): a. Relapsing-remitting MS, and failure of all of the following at up to maximally indicated doses, unless clinically significant adverse effects are experienced or all are contraindicated (i, ii, iii, and iv):
   i. Dimethyl fumarate (generic Tecfidera®);
   ii. Teriflunomide (generic Aubagio®);
   iii. Fingolimod (Gilenya®); iv. 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 b. Secondary progressive MS;

2. Prescribed by or in consultation with a neurologist;

   3. Age ≥ 18 years; Page 1 of 8

   CLINICAL POLICY Cladribine

3. Mavenclad 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;
5. Dose does not exceed any of the following:
   a. 2 tablets per day; b. 10 tablets per cycle;
   c. 2 cycles per course; d. 1 course per year. Approval duration: 12 months - up to 1 course (2 courses lifetime total) 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): 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
7. 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):
8. 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);

9. 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. Mavenclad is not prescribed concurrently with other disease modifying therapies for MS (see Appendix D); Page 2 of 8

   CLINICAL POLICY Cladribine

10. Dose does not exceed any of the following:
    a. 2 tablets per day; b. 10 tablets per cycle;
    c. 2 cycles per course; d. 1 course per year. Approval duration: 12 months - up to 1 course (2 courses lifetime total) 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 policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents; B. CIS. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key CIS: clinically isolated syndrome 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 teriflunomide (Aubagio®) Avonex®, Rebif® (interferon beta-1a) 7 mg or 14 mg PO QD Avonex: 30 mcg IM Q week Rebif: 22 mcg or 44 mcg SC TIW Page 3 of 8 Dose Limit/ Maximum Dose 14 mg/day Avonex: 30 mcg/week Rebif: 44 mcg TIW

    CLINICAL POLICY Cladribine Drug Name Dosing Regimen Dose Limit/ Maximum Dose 250 mg QOD 250 mcg SC QOD 125 mcg SC Q2 weeks Betaseron®, Extavia® (interferon beta-1b) Plegridy® (peginterferon beta-1a) glatiramer acetate (Copaxone®, Glatopa®) fingolimod (Gilenya®) dimethyl fumarate (Tecfidera®) 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. 0.5 mg PO QD 120 mg PO BID for 7 days, followed by 240 mg PO BID 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/2 weeks Appendix C: Contraindications/Boxed Warnings • Contraindication(s): o Patients with current malignancy o Pregnant women, and women and men of reproductive potential who do not plan to use effective contraception during Mavenclad dosing and for 6 months after the last dose in each treatment course o HIV infection o Active chronic infections (e.g., hepatitis or tuberculosis) o History of hypersensitivity to cladribine o Women intending to breastfeed on a Mavenclad treatment day and for 10 days after the last dose • Boxed warning(s):
    o Malignancies o Risk of teratogenicity 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®). V. Dosage and Administration
    Indication Dosing Regimen Relapsing MS DOSAGE ADMINISTRATION OVERVIEW • Cumulative dosage of 3.5 mg/kg PO divided into 2 yearly treatment COURSES (1.75 mg/kg per treatment course).
    Maximum Dose 2 tablets/day, 10 tablets/cycle, 2 cycles/course/year, 2 courses total Page 4 of 8

    CLINICAL POLICY Cladribine Indication Dosing Regimen Maximum Dose • Each treatment COURSE is divided into 2 treatment CYCLES.
    • See dosage chart in package insert and below for number of tablets per CYCLE based on body weight in kg. • Administer the CYCLE dosage as 1 or 2 tablets once daily over 4 or 5 consecutive days. Do not administer more than 2 tablets daily. Separate administration from any other oral drug by at least 3 hours.
    • Following the administration of 2 treatment COURSES, do not administer additional Mavenclad treatment during the next 2 years. Treatment during these 2 years may further increase the risk of malignancy. The safety and efficacy of reinitiating Mavenclad more than 2 years after completing 2 treatment courses has not been studied. COURSES AND CYCLES • COURSE ONE (year one) o First CYCLE: start any time. o Second CYCLE: start 23 to 27 days after last dose of first cycle. • COURSE TWO (year two) o First CYCLE: start at least 43 weeks after last dose of first course’s second cycle. o Second CYCLE: start 23 to 27 days after the last dose of second course’s first cycle. WEIGHT RANGE (KG): # OF TABLETS - FIRST AND SECOND CYCLES • 40* to less than 50 kg o 40 mg (4 tablets) (cycles 1 and 2) • 50 to less than 60 kg o 50 mg (5 tablets) (cycles 1 and 2) • 60 to less than 70 kg o 60 mg (6 tablets) (cycles 1 and 2) • 70 to less than 80 kg o 70 mg (7 tablets) (cycles 1 and 2) • 80 to less than 90 kg o 80 mg (8 tablets) (cycle 1) o 70 mg (7 tablets) (cycle 2) • 90 to less than 100 kg o 90 mg (9 tablets) (cycle 1) o 80 mg (8 tablets) (cycle 2) Page 5 of 8

    CLINICAL POLICY Cladribine Indication Dosing Regimen Maximum Dose • 100 to less than 110 kg o 100 mg (10 tablets) (cycle 1) o 90 mg (9 tablets) (cycle 2) • 110 kg and above o 100 mg (10 tablets) (cycles 1 and 2) *The use of Mavenclad in patients weighing less than 40 kg has not been investigated. VI. Product Availability
    Tablet: 10 mg VII.