MIRCERA, Methoxy Polyethylene Glycol-Epoetin Beta Form

Methoxy polyethylene glycol-epoetin beta (Mircera®) is an erythropoiesis-stimulating agent (ESA). FDA Approved Indication(s) Mircera is indicated for the treatment of anemia associated with chronic kidney disease (CKD) in: • Adult patients on dialysis and patients not on dialysis • Pediatric patients 5 to 17 years of age on hemodialysis who are converting from another ESA after their hemoglobin level was stabilized with an ESA Limitation(s) of use:
• Mircera is not indicated and is not recommended for use: o In the treatment of anemia due to cancer chemotherapy
o As a substitute for red blood cell (RBC) transfusions in patients who require immediate correction of anemia. • Mircera has not been shown to improve symptoms, physical functioning or health-related quality of life. 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 Mircera is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Anemia of Chronic Kidney Disease (must meet all):

1. Diagnosis of anemia of CKD, and member meets one of the following (a or b): a. Age ≥ 18 years (dialysis status is irrelevant); b. Age 5 years to ≤ 17 years, on hemodialysis, and will be converting from another ESA agent (e.g., epoetin alfa, darbepoetin alfa)
2. Prescribed by or in consultation with a hematologist or nephrologist;
   3. Adequate iron stores as indicated by current (within the last 3 months) serum ferritin level ≥ 100 mcg/L or serum transferrin saturation ≥ 20%;

3. Pretreatment hemoglobin < 10 g/dL; Page 1 of 7

   CLINICAL POLICY Methoxy Polyethylene Glycol-Epoetin Beta

4. One of the following (a or b): a. Failure of Retacrit®, unless contraindicated or clinically significant adverse effects are experienced; Prior authorization may be required for Retacrit
   b. If Retacrit is unavailable due to shortage, failure of Epogen®, unless contraindicated or clinically significant adverse effects are experienced; Prior authorization may be required for Epogen
5. Dosing interval does not exceed one of the following (a or b): a. Adults: SC or IV once every two weeks; b. Pediatrics: IV once every four weeks. Approval duration:
   Medicaid/HIM – 6 months Commercial – 6 months or to member’s renewal period, whichever is longer 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. Anemia of Chronic Kidney Disease (must meet all):

   1. 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 is responding positively to therapy;
   3. One of the following (a or b): a. Failure of Retacrit, unless contraindicated or clinically significant adverse effects are experienced; *Prior authorization may be required for Retacrit
      b. If Retacrit is unavailable due to shortage, failure of Epogen, unless contraindicated or clinically significant adverse effects are experienced; Page 2 of 7

   CLINICAL POLICY Methoxy Polyethylene Glycol-Epoetin Beta *Prior authorization may be required for Epogen

8. Adequate iron stores as indicated by current (within the last 3 months) serum ferritin level ≥ 100 mcg/L or serum transferrin saturation ≥ 20%;
   5. Dosing interval does not exceed one of the following (a or b): a. Adults: SC or IV once every two weeks; b. Pediatrics: IV once every four weeks. Approval duration:
      Medicaid/HIM – 6 months Commercial – 6 months or to member’s renewal period, whichever is longer B. 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.
    III. Diagnoses/Indications for which coverage is NOT authorized:
    A. Anemia due to cancer chemotherapy; B. 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.
    IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key CKD: chronic kidney disease
    ESA: erythropoiesis-stimulating agent
    FDA: Food and Drug Administration
    RBC: red blood cell 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 and may require prior authorization.
    Page 3 of 7

    CLINICAL POLICY Methoxy Polyethylene Glycol-Epoetin Beta Drug Name Dosing Regimen Retacrit® (epoetin alfa-epbx), Epogen® (epoetin alfa) Anemia due to CKD Initial dose: 50 to 100 Units/kg 3 times weekly (adults) IV or SC and 50 Units/kg 3 times weekly (pediatric patients ages 1 month or older) IV or SC. Individualize maintenance dose. IV route recommended for patients on hemodialysis Dose Limit/ Maximum Dose Varies depending on indication, frequency of administration, and individual response 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 Uncontrolled hypertension o Pure red cell aplasia (PRCA) that begins after treatment with erythropoietin protein drugs o Allergic reactions, anaphylaxis • Boxed warning(s): ESAs increase the risk of death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access and tumor progression or recurrence Appendix D: General Information • The 2012 Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Anemia in Chronic Kidney Disease state that there is no evidence that any given ESA brand is superior to another in terms of patient outcomes. It is considered opinion of the Work Group that the likelihood of differences in clinical outcomes among ESA brands is low. The guideline recommends choosing an ESA based on the balance of pharmacodynamics, safety information, clinical outcome data, costs, and availability (Level 1, Grade D recommendation). V. Dosage and Administration
    Indication Anemia due to CKD Dosing Regimen Adult patients with CKD on or not on dialysis Initial treatment: 0.6 mcg/kg body weight SC or IV once every two weeks
    Maximum Dose Varies Maintenance treatment: dose twice that of the every- two-week dose SC or IV once monthly
    Conversion from another ESA: dosed SC or IV once monthly or once every two weeks based on total weekly epoetin alfa or darbepoetin alfa dose at time of conversion Page 4 of 7

    CLINICAL POLICY Methoxy Polyethylene Glycol-Epoetin Beta Indication Dosing Regimen Pediatric patients with CKD on hemodialysis Conversion from another ESA: dosed IV once every four weeks based on total weekly epoetin alfa or darbepoetin alfa dose at time of conversion.
    Maximum Dose VI. Product Availability
    Injection (single-dose prefilled syringe): 30, 50, 75, 100, 120, 150, 200, or 250 mcg in 0.3 mL solution; 360 mcg in 0.6 mL solution VII.