BENLYSTA, Belimumab Form

Belimumab (Benlysta®) is B-lymphocyte stimulator specific inhibitor. FDA Approved Indication(s) Benlysta is indicated for the treatment of: • Patients aged 5 years and older with active, autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy. • Patients aged 5 years and older with active lupus nephritis (LN) who are receiving standard therapy. Limitation(s) of use: The efficacy of Benlysta has not been evaluated in patients with severe active central nervous system lupus. Use of Benlysta is not recommended in this situation. 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 Benlysta is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Systemic Lupus Erythematosus (must meet all):

1. Diagnosis of SLE;
   2. Prescribed by or in consultation with a rheumatologist;
   3. Age ≥ 5 years;
   4. Documentation confirms that member is positive for an SLE autoantibody (e.g., anti- nuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA), anti-Smith (anti- Sm), anti-ribonucleoprotein (anti-RNP), anti-Ro/SSA, anti-La/SSB, antiphospholipid antibody);
2. Prescribed in combination with standard therapy for SLE that includes one or more of the following agents, unless all agents are contraindicated: glucocorticoids (e.g., prednisone), antimalarial (e.g., hydroxychloroquine or chloroquine), non-biologic immunosuppressants (e.g., azathioprine, methotrexate, mycophenolate);

3. Request meets one of the following (a or b): a. Adults (≥ 18 years of age):
   i. IV: Dose does not exceed 10 mg/kg per dose at 2-week intervals for the first 3 doses and at 4-week intervals thereafter; ii. SC: 200 mg per week; Page 1 of 7

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   Belimumab b. Pediatrics (≥ 5 years of age): Dose does not exceed 10 mg/kg per dose IV at 2- week intervals for the first 3 doses and at 4-week intervals thereafter. Approval duration:
   Medicaid/HIM – 6 months Commercial – 6 months or to member’s renewal date, whichever is longer B. Lupus Nephritis (must meet all):

4. Diagnosis of LN with kidney biopsy that confirms one of the following (a, b, or c): a. LN Class III (focal); b. LN Class IV (diffuse segmental or global); c. LN Class V (membranous);
5. Prescribed by or in consultation with a nephrologist or rheumatologist;
   3. Age ≥ 5 years;
   4. Member has a confirmed diagnosis of systemic lupus erythematosus;
   5. Prescribed in combination with standard therapy for SLE that includes one or more of the following agents, unless all agents are contraindicated: glucocorticoids (e.g., prednisone), antimalarial (e.g., hydroxychloroquine or chloroquine), non-biologic immunosuppressants (e.g., azathioprine, cyclophosphamide, methotrexate, mycophenolate);
6. Request meets one of the following (a or b): a. IV: Dose does not exceed 10 mg/kg per dose at 2-week intervals for the first 3 doses and at 4-week intervals thereafter; b. SC in adults (≥ 18 years of age): Dose does not exceed 400 mg per week SC for the first 4 doses, then 200 mg/week SC; Loading doses not permitted if previously receiving Benlysta for treatment of SLE Approval duration:
   Medicaid/HIM – 6 months Commercial – 6 months or to member’s renewal date, whichever is longer C. 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.
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   Belimumab II. Continued Therapy A. All Indications in Section I (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. For SLE: Member is responding positively to therapy; b. For LN: Member is responding positively to therapy as evidenced by one of the following (i, ii, or iii): i. Reduced level of proteinuria measured by UPCR ≤ 0.5 mg/mg from baseline with low dose steroids (e.g., prednisone); ii. No reduction from baseline in eGFR of greater than 20% with low dose steroids (e.g., prednisone); iii. eGFR ≥ 60 mL/min/1.73 m2 with low dose steroids (e.g., prednisone);
   3. Prescribed in in combination with standard therapy for SLE that includes one or more of the following agents, unless all agents are contraindicated: glucocorticoids (e.g., prednisone), antimalarial (e.g., hydroxychloroquine or chloroquine), non-biologic immunosuppressants (e.g., azathioprine, methotrexate, mycophenolate);
   4. If request is for a dose increase, request meets one of the following (a or b): a. Adults (≥ 18 years of age):
      i. IV: Dose does not exceed 10 mg/kg per dose at 2-week intervals for the first 3 doses and at 4-week intervals thereafter; ii. SC: 200 mg per week; b. Pediatrics (≥ 5 years of age): Dose does not exceed 10 mg/kg per dose IV at 2- week intervals for the first 3 doses and at 4-week intervals thereafter. Approval duration:
      Medicaid/HIM – 12 months Commercial – 6 months or to member’s renewal date, whichever is longer B. Other diagnoses/indications (must meet 1 or 2):

10. 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 3 of 7

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    Belimumab

11. 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. Autoantibody negative SLE.
    IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ANA: anti-nuclear antibody
    Anti-dsDNA: anti-double-stranded DNA Anti-Sm: anti-Smith DNA: deoxyribonucleic acid FDA: Food and Drug Administration LN: lupus nephritis SLE: systemic lupus erythematosus 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 glucocorticoids (e.g., prednisone) antimalarial agents (e.g., hydroxychloroquine, chloroquine) non-biologic immunosuppressants (e.g., azathioprine, methotrexate, mycophenolate)* 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.

    • For LN, cyclophosphamide is also an acceptable immunosuppressant. Dosing Regimen Varies Varies Varies Dose Limit/ Maximum Dose Varies Varies Varies Appendix C: Contraindications/Boxed Warnings • Contraindication(s): previous anaphylaxis to belimumab • Boxed warning(s): none reported Appendix D: Autoantibody Positive Versus Negative SLE Only one of the five Benlysta pivotal trials included patients with autoantibody negative SLE; no significant differences between any of the Benlysta groups and the placebo group were observed. However, on further analysis Benlysta appeared to offer benefit to a subgroup of autoantibody positive patients. Benlysta’s efficacy was confirmed in the remaining four trials which included only autoantibody positive patients. Because of the apparent lack of efficacy in autoantibody negative patients and because the FDA has approved Benlysta in Page 4 of 7

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    Belimumab only autoantibody positive patients, Benlysta coverage will not be authorized for patients with autoantibody negative SLE.
    V. Dosage and Administration
    Indication Dosing Regimen • SLE, LN IV (pediatrics and adults) o 10 mg/kg at 2 week intervals for the first 3 doses and at 4 week intervals thereafter Maximum Dose IV: 10 mg/kg/dose
    SC: 200 mg/week
    • SC (adults only) o For SLE, 200 mg once weekly o For LN, 400 mg once weekly for 4 doses, then 200 mg once weekly • Transition from IV to SC therapy (adults) o May transition from IV to SC therapy any time after the first 2 IV doses; administer first SC dose 1 to 2 weeks after the last IV dose VI. Product Availability
    • Single-dose vial: 120 mg and 400 mg lyophilized powder for reconstitution • Single-dose prefilled autoinjector/syringe: 200 mg/mL VII.