OCREVUS, Ocrelizumab Form

Ocrelizumab (Ocrevus®) is a CD20-directed cytolytic antibody.
FDA Approved Indication(s) Ocrevus 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
• Primary progressive MS, 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 Ocrevus 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, b, c, or d): 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 †Betaseron is preferred for the Commercial and HIM lines of business; Extavia is preferred for the Medicaid line of business c. Secondary progressive MS d. Primary progressive MS;

2. Prescribed by or in consultation with a neurologist;

   3. Age ≥ 18 years; Page 1 of 8

   CLINICAL POLICY Ocrelizumab

3. Ocrevus 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. 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);
6. Dose does not exceed the following:
   a. Initial dose: 300 mg, followed by a second 300 mg dose 2 weeks later; b. Maintenance dose: 600 mg every 6 months. Approval duration:
   Medicaid/HIM – 6 months Commercial – 6 months or to the member’s renewal date, whichever is longer B. Other diagnoses/indications (must meet 1 or 2):
7. 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
8. 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):

9. 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);

   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; Page 2 of 8

   CLINICAL POLICY Ocrelizumab 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;

10. Ocrevus 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 600 mg every 6 months. 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 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, 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

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, 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. Rheumatoid arthritis; C. Lupus nephritis/systemic lupus erythematosus. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key EDSS: expanded disability status scale
    FDA: Food and Drug Administration MS: multiple sclerosis Page 3 of 8

    CLINICAL POLICY Ocrelizumab 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 125 mcg/2 weeks 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 teriflunomide (Aubagio®) 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 mcg SC QOD 250 mg QOD Appendix C: Contraindications/Boxed Warnings • Contraindication(s): active hepatitis B virus infection; history of life-threatening infusion reaction to Ocrevus • 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 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 May 2010, the manufacturers of Ocrevus discontinued the Ocrevus clinical developmental program in rheumatoid arthritis due to unfavorable overall benefit to risk profile. The program was initially suspended in March following recommendation from an independent data and safety monitoring board, which concluded that the safety risk outweighed the benefits observed in patients with rheumatoid arthritis based on an infection related safety signal which included serious infections, some of which were fatal, and opportunistic infections.
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    CLINICAL POLICY Ocrelizumab • The BELONG phase 3 study (Mysler EF et al., 2013) evaluating use of Ocrevus in patients with lupus nephritis due to systemic lupus erythematosus was also terminated early due to an imbalance of serious and opportunistic infections in the Ocrevus treated patients versus the placebo arm. From an analysis of an incomplete data set, there was no statistically significant differentiation between the Ocrevus and placebo response rates. V. Dosage and Administration
    Indication Relapsing and primary progressive MS
    Dosing Regimen Initial 300 mg IV infusion with a second 300 mg IV infusion two weeks later, followed by subsequent doses of 600 mg via IV infusion every 6 months Maximum Dose 600 mg/6 months VI. Product Availability
    Single-dose vial: 300 mg/10 mL VII.