Ofatumumab (Arzerra®, Kesimpta®) Form

Ofatumumab (Arzerra®, Kesimpta®) is a CD20-directed cytolytic monoclonal antibody. FDA Approved Indication(s) Arzerra is indicated: • In combination with chlorambucil, for the treatment of previously untreated patients with chronic lymphocytic leukemia (CLL) for whom fludarabine-based therapy is considered inappropriate In combination with fludarabine and cyclophosphamide for the treatment of patients with relapsed CLL • • For extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive CLL • For the treatment of patients with CLL refractory to fludarabine and alemtuzumab Kesimpta is indicated for the treatment of 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 Arzerra and Kesimpta are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Chronic Lymphocytic Leukemia (must meet all):

1. Diagnosis of CLL;

   2. Request is for Arzerra;
   3. Prescribed by or in consultation with an oncologist or hematologist;
   4. Age ≥ 18 years;
   5. One of the following (a, b, c, or d): a. Both of the following (i and ii): i. Prescribed as first-line therapy in combination with chlorambucil; ii. Fludarabine-based therapy is considered inappropriate; b. Prescribed in combination with fludarabine and cyclophosphamide for relapsed disease; Page 1 of 10

   CLINICAL POLICY Ofatumumab c. Member is in complete or partial response after at least two lines of therapy for recurrent or progressive disease; d. Disease is refractory to fludarabine and alemtuzumab;

2. Request meets one of the following (a or b): a. Dose does not exceed the maximum indicated in section V; b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN. Approval duration:
   Medicaid/HIM – 6 months Commercial – 6 months or to the member’s renewal date, whichever is longer
   B. Waldenstrom’s Macroglobulinemia/Lymphoplasmacytic Lymphoma (off-label)
   (must meet all):
   
   1. Diagnosis of Waldenstrom’s macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL);
3. Request is for Arzerra;
   3. Prescribed by or in consultation with an oncologist or hematologist;
   4. Age ≥ 18 years;
   5. Member is rituximab-intolerant;
   6. Request is for second-line or subsequent therapy (see Appendix B for examples of prior therapy);

4. Dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).Prescribed regimen must be FDA-approved or recommended by NCCN.
   Approval duration:
   Medicaid/HIM – 6 months Commercial – 6 months or to the member’s renewal date, whichever is longer
   C. Multiple Sclerosis (must meet all):The criteria below do not apply to Arizona Complete Health Medicaid (AzCH-CCP) line of business. Please refer to AZ.CP.PHAR.1020 for multiple sclerosis requests for AzCH-CCP members.

   1. Diagnosis of one of the following (a, b, or c): a. Clinically isolated syndrome, and 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 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 Page 2 of 10

   CLINICAL POLICY Ofatumumab †Betaseron is preferred for the Commercial and HIM lines of business; Extavia is preferred for the Medicaid line of business c. Secondary progressive MS;

5. Request is for Kesimpta;
   3. Prescribed by or in consultation with a neurologist;
   4. Age ≥ 18 years;
   5. Kesimpta is not prescribed concurrently with other disease modifying therapies for MS (see Appendix D);
6. Documentation of both baseline number of relapses per year and expanded disability status scale (EDSS) score;
7. 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);
8. Dose does not exceed the following:
   a. Initial dose: 20 mg, followed by 20 mg doses 1 and 2 weeks later; b. Maintenance dose: 20 mg every 4 weeks. Approval duration:
   Medicaid/HIM – 6 months Commercial – 6 months or to the member’s renewal date, whichever is longer D. 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.
    II. Continued Therapy A. All Indications in Section I Other Than Multiple Sclerosis (must meet all):
11. Currently receiving Arzerra via Centene benefit, or documentation supports that member is currently receiving Arzerra for a covered indication and has received this medication for at least 30 days;

12. Member is responding positively to therapy;

    3. If request is for a dose increase, request meets one of the following (a or b):* a. New dose does not exceed the maximum indicated in section V; b. New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Page 3 of 10

    CLINICAL POLICY Ofatumumab Prescribed regimen must be FDA-approved or recommended by NCCN.
    Approval duration:
    Medicaid/HIM – 12 months Commercial – 6 months or to the member’s renewal date, whichever is longer B. Multiple Sclerosis (must meet all): *The criteria below do not apply to Arizona Complete Health Medicaid (AzCH-CCP) line of business. Please refer to AZ.CP.PHAR.1020 for multiple sclerosis requests for AzCH-CCP members.

    1. Member meets one of the following (a or b): a. Currently receiving Kesimpta 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);
    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, 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;
13. Kesimpta is not prescribed concurrently with other disease modifying therapies for MS (see Appendix D);
14. If request is for a dose increase, new dose does not exceed 20 mg every 4 weeks. Approval duration:
    Medicaid/HIM –
    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 Commercial – 6 months or to the member’s renewal date, whichever is longer C. Other diagnoses/indications (must meet 1 or 2):

15. 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 Page 4 of 10

    CLINICAL POLICY Ofatumumab

16. 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. Primary progressive MS.
    IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key CLL: chronic lymphocytic leukemia EDSS: Expanded Disability Status Scale FDA: Food and Drug Administration MS: multiple sclerosis NCCN: National Comprehensive Cancer Network WM/LPL: Waldenstrom’s macroglobulinemia /lymphoplasmacytic lymphoma 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 Varies Varies WM/LPL primary therapy examples: • bendamustine/rituximab • bortezomib (Velcade®)/dexamethasone/ rituximab Imbruvica® (ibrutinib) ± rituximab rituximab/cyclophosphamide/ dexamethasone • • MS therapies teriflunomide (Aubagio) Avonex, Rebif (interferon beta- 1a) Plegridy (peginterferon beta-1a) Betaseron, Extavia (interferon beta-1b) glatiramer acetate (Copaxone, Glatopa) 7 mg or 14 mg PO QD Avonex: 30 mcg IM Q week Rebif: 22 mcg or 44 mcg SC TIW 125 mcg SC Q2 weeks 250 mcg SC QOD 14 mg/day Avonex: 30 mcg/week Rebif: 44 mcg TIW 125 mcg/2 weeks 250 mg QOD 20 mg SC QD or 40 mg SC TIW 20 mg/day or 40 mg TIW Page 5 of 10

    CLINICAL POLICY Ofatumumab Drug Name Dosing Regimen fingolimod (Gilenya) dimethyl fumarate (Tecfidera) 0.5 mg PO QD 120 mg PO BID for 7 days, followed by 240 mg PO BID Dose Limit/ Maximum Dose 0.5 mg/day 480 mg/day 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. Appendix C: Contraindications/Boxed Warnings • Contraindication(s):
    o Arzerra: none reported o Kesimpta: active hepatitis B virus infection • Boxed warning(s):
    o Arzerra: hepatitis B virus reactivation, progressive multifocal leukoencephalopathy o Kesimpta: 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 clinically isolated syndrome, only the interferon products, glatiramer, and teriflunomide have demonstrated any efficacy in decreasing the risk of conversion to MS compared to placebo. This is supported by the American Academy of Neurology 2018 MS guidelines. In August 2020, Novartis announced their plan to transition Arzerra to an oncology patient access program will provide Arzerra at no cost to CLL patients in the U.S. Arzerra is no longer available for commercial purchase. • V. Dosage and Administration
    Indication Drug Name Dosing Regimen Ofatumumab (Arzerra) Previously untreated CLL Relapsed CLL In combination with chlorambucil: 300 mg IV on Day 1 followed by 1,000 mg IV on Day 8 (Cycle 1). Then 1,000 mg IV on Day 1 of subsequent 28-day cycles for a minimum of 3 cycles until best response or a maximum of 12 cycles In combination with fludarabine and cyclophosphamide: 300 mg IV on Day 1 followed by 1,000 mg IV on Day 8 (Cycle 1). Then 1,000 mg IV on Day 1 Maximum Dose 12 cycles 6 cycles Page 6 of 10

    CLINICAL POLICY Ofatumumab Drug Name Indication Dosing Regimen Extended treatment in CLL Refractory CLL Ofatumumab (Kesimpta) MS VI. Product Availability
    Drug Name Ofatumumab (Arzerra) Ofatumumab (Kesimpta) of subsequent 28-day cycles for a maximum of 6 cycles 300 mg on Day 1 followed by 1,000 mg 1 week later on Day 8, followed by 1,000 mg 7 weeks later and every 8 weeks thereafter for up to a maximum of 2 years 300 mg initial dose, followed 1 week later by 2,000 mg weekly for 7 doses, followed 4 weeks later by 2,000 mg every 4 weeks for 4 doses 20 mg SC at weeks 0, 1, and 2, followed by 20 mg SC monthly starting at week 4 Maximum Dose 2 years 12 doses 20 mg Availability Single-use vials: 100 mg/5 mL, 1,000 mg/50 mL Single-dose prefilled Sensoready pen or prefilled syringe: 20 mg/0.4 mL VII.