ARANESP ALBUMIN FREE, Darbepoetin Alfa Form

Darbepoetin alfa (Aranesp®) is an erythropoiesis-stimulating agent (ESA).
FDA Approved Indication(s) Aranesp is indicated for the treatment of: • Anemia due to chronic kidney disease (CKD), including patients on dialysis and patients not on dialysis. • Anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy. Limitation(s) of use: Aranesp has not been shown to improve quality of life, fatigue, or patient well-being. Aranesp is not indicated for use:
• In patients with cancer receiving hormonal agents, biologic products, or radiotherapy, unless also receiving concomitant myelosuppressive chemotherapy.
In patients with cancer receiving myelosuppressive chemotherapy when the anticipated outcome is cure.
In patients with cancer receiving myelosuppressive chemotherapy in whom the anemia can be managed by transfusion.
• • • As a substitute for red blood cell transfusions in patients who require immediate correction of anemia.
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 Aranesp is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Anemia due to Chronic Kidney Disease (must meet all):

1. Diagnosis of anemia of CKD (dialysis and non-dialysis members);
   
   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%;

2. Pretreatment hemoglobin level < 10 g/dL; Page 1 of 12

   CLINICAL POLICY Darbepoetin Alfa

3. Member meets 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 Approval duration:
   Medicaid/HIM – 6 months Commercial – 6 months or to member’s renewal period, whichever is longer B. Anemia due to Chemotherapy in Patients with Cancer (must meet all):
4. Request is for use in solid or non-myeloid malignancies;
   2. Member is receiving myelosuppressive chemotherapy without curative intent;
   3. Prescribed by or in consultation with a hematologist or oncologist;
   4. Age ≥ 18 years;
   5. Adequate iron stores as indicated by current (within the last 3 months) serum ferritin level ≥ 100 mcg/L or serum transferrin saturation ≥ 20%;
5. Pretreatment hemoglobin < 10 g/dL;
   
   7. Member meets one of the following (a or b): a. One of the following (i or ii): i. Failure of Retacrit, unless contraindicated or clinically significant adverse effects are experienced; Prior authorization may be required for Retacrit
      ii. 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
      b. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix D). Approval duration:
      Medicaid/HIM – 6 months or until the completion of chemotherapy course (whichever is less) Commercial – Until the completion of chemotherapy course, 6 months, or to member’s renewal date, whichever is longer
      C. Anemia Associated with Myelodysplastic Syndrome (off-label) (must meet all):
6. Diagnosis of anemia from myelodysplastic syndrome (MDS);
   2. Prescribed by or in consultation with a hematologist or oncologist;
   3. Age ≥ 18 years;
   4. One of the following (a or b): a. Current (within the last 3 months) serum erythropoietin (EPO) ≤ 500 mU/mL; b. Member has lower risk (IPSS low/intermediate-1) disease associated with symptomatic anemia with del(5q);
7. Adequate iron stores as indicated by current (within the last 3 months) serum ferritin level ≥ 100 mcg/L or serum transferrin saturation ≥ 20%;

8. Pretreatment hemoglobin < 10 g/dL; Page 2 of 12

   CLINICAL POLICY Darbepoetin Alfa

9. Member meets one of the following (a or b): a. One of the following (i or ii): i. Failure of Retacrit, unless contraindicated or clinically significant adverse effects are experienced; Prior authorization may be required for Retacrit
   ii. 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
   b. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix D). Approval duration:
   Medicaid/HIM – 6 months Commercial – 6 months or to member’s renewal period, whichever is longer D. Myelofibrosis-Associated Anemia (off-label) (must meet all):
10. Diagnosis of anemia associated with myelofibrosis;
    2. Prescribed by or in consultation with a hematologist or oncologist;
    3. Age ≥ 18 years;
    4. Current (within the last 3 months) serum EPO < 500 mU/mL;
    5. Adequate iron stores as indicated by current (within the last 3 months) serum ferritin level ≥ 100 mcg/L or serum transferrin saturation ≥ 20%;
11. Member meets one of the following (a or b): a. One of the following (i or ii): i. Failure of Retacrit, unless contraindicated or clinically significant adverse effects are experienced; Prior authorization may be required for Retacrit
    ii. 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
    b. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix D). Approval duration:
    Medicaid/HIM – 6 months Commercial – 6 months or to member’s renewal period, whichever is longer E. Other diagnoses/indications (must meet all):

12. Member meets one of the following (a or b): a. One of the following (i or ii): i. Failure of Retacrit, unless contraindicated or clinically significant adverse effects are experienced; Prior authorization may be required for Retacrit
    ii. 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
    b. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix D); Page 3 of 12

    CLINICAL POLICY Darbepoetin Alfa

13. Member meets one of the following (a or b): a. 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 (i or ii): i. 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 ii. 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 b. 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 due to Chronic Kidney Disease (must meet all):
14. 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; Prior authorization may be required for Epogen
15. Adequate iron stores as indicated by current (within the last 3 months) serum ferritin level ≥ 100 mcg/L or serum transferrin saturation ≥ 20%.
    Approval duration:
    Medicaid/HIM – 6 months Commercial – 6 months or to member’s renewal period, whichever is longer B. Anemia due to Chemotherapy in Patients with Cancer (must meet all):

16. 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); Page 4 of 12

    CLINICAL POLICY Darbepoetin Alfa

17. Member meets one of the following (a or b): a. One of the following (i or ii): i. Failure of Retacrit, unless contraindicated or clinically significant adverse effects are experienced; Prior authorization may be required for Retacrit
    ii. 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
    b. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix D);
18. Continuation of ESA therapy is concurrent with myelosuppressive chemotherapy;
    
    4. If member has received ≥ 8 weeks of ESA therapy, member meets both of the following (a and b): a. Documented response to therapy as evidenced by a rise in hemoglobin levels > 1 g/dL;
       b. No RBC transfusions are required;
19. Current hemoglobin < 10 g/dL;
    6. Adequate iron stores as indicated by current (within the last 3 months) serum ferritin level ≥ 100 mcg/L or serum transferrin saturation ≥ 20%.
       Approval duration:
       Medicaid/HIM – 6 months or until the completion of chemotherapy course (whichever is less) Commercial – Until the completion of chemotherapy course, 6 months, or to member’s renewal date, whichever is longer
       C. Anemia Associated with Myelodysplastic Syndrome (off-label) (must meet all):
20. 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. One of the following (i or ii): i. Failure of Retacrit, unless contraindicated or clinically significant adverse effects are experienced; Prior authorization may be required for Retacrit
       ii. 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
       b. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix D);

21. If member has received ≥ 8 weeks of ESA therapy, member meets one of the following (a or b): a. Documented response to therapy as evidenced by a rise in hemoglobin levels > 1.5 g/dL;
    b. Decrease of RBC transfusions requirement; Page 5 of 12

    CLINICAL POLICY Darbepoetin Alfa

22. Current hemoglobin ≤ 12 g/dL;
    
    5. Adequate iron stores as indicated by current (within the last 3 months) serum ferritin level ≥ 100 mcg/L or serum transferrin saturation ≥ 20%.
       Approval duration:
       Medicaid/HIM – 6 months Commercial – 6 months or to member’s renewal period, whichever is longer D. Myelofibrosis-Associated Anemia (off-label) (must meet all):
23. 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);
24. Member is responding positively to therapy (examples may include, but are not limited to: for transfusion-independent members with a baseline hemoglobin < 10 g/dL, a ≥ 2 g/dL increase in hemoglobin; or for previously transfusion-dependent members, transitioning to become transfusion-independent);
25. Member meets one of the following (i or ii): a. One of the following (i or ii): i. Failure of Retacrit, unless contraindicated or clinically significant adverse effects are experienced; Prior authorization may be required for Retacrit
    ii. 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
    b. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix D);
26. Adequate iron stores as indicated by current (within the last 3 months) serum ferritin level ≥ 100 mcg/L or serum transferrin saturation ≥ 20%. Approval duration:
    Medicaid/HIM – 6 months Commercial – 6 months or to member’s renewal period, whichever is longer E. Other diagnoses/indications (must meet all):

27. Member meets one of the following (a or b): a. One of the following (i or ii): i. Failure of Retacrit, unless contraindicated or clinically significant adverse effects are experienced; Prior authorization may be required for Retacrit
    ii. 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
    b. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix D); Page 6 of 12

    CLINICAL POLICY Darbepoetin Alfa

28. Member meets one of the following (a or b): a. 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 (i or ii): i. 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 ii. 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 b. 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.
    IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key CKD: chronic kidney disease EPO: erythropoietin ESA: erythropoiesis-stimulating agent FDA: Food and Drug Administration IPSS: International Prognostic Scoring System MDS: myelodysplastic syndrome
    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.
    Drug Name Dosing Regimen Dose Limit/ Maximum Dose Varies depending on indication, frequency of administration, and individual response 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 Page 7 of 12

    CLINICAL POLICY Darbepoetin Alfa Drug Name Dosing Regimen Dose Limit/ Maximum Dose Anemia due to chemotherapy 40,000 Units SC weekly or 150 Units/kg SC 3 times weekly (adults); 600 Units/kg IV weekly (pediatric patients 5 to 18 years) until completion of a chemotherapy course Anemia associated with MDS† 40,000 to 60,000 Units SC 1-2 times weekly
    Anemia associated with myelofibrosis† In a clinical trial, patients initially received erythropoietin 10,000 units SC 3 days per week. Erythropoietin was increased to 20,000 units 3 days per week if a response was not obtained after 2 months and erythropoietin was discontinued in patients who did not experience a response at 3 months. 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. †Off-label indication Appendix C: Contraindications/Boxed Warnings • Contraindication(s): uncontrolled hypertension, pure red cell aplasia that begins after treatment with Aranesp or other erythropoietin protein drugs, serious allergic reactions • 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: States with Regulations against Redirections in Certain Oncology Settings State Step Therapy Prohibited? Yes Yes FL GA IA LA NV OH Yes Yes Yes Yes Notes For stage 4 metastatic cancer and associated conditions. For stage 4 metastatic cancer. Redirection does not refer to review of medical necessity or clinical appropriateness. For standard of care stage 4 cancer drug use, supported by peer- reviewed, evidence-based literature, and approved by FDA. For stage 4 advanced, metastatic cancer or associated conditions. Exception if “clinically equivalent therapy, contains identical active ingredient(s), and proven to have same efficacy. Stage 3 and stage 4 cancer patients for a prescription drug to treat the cancer or any symptom thereof of the covered person Applies to Commercial and HIM requests only Page 8 of 12

    CLINICAL POLICY Darbepoetin Alfa State Step Therapy Prohibited? Notes OK PA TN TX Yes Yes Yes Yes For stage 4 metastatic cancer and associated conditions Applies to HIM requests only For advanced metastatic cancer and associated conditions For stage 4 advanced, metastatic cancer For advanced metastatic cancer and associated conditions For stage 4 advanced, metastatic cancer and associated conditions V. Dosage and Administration
    Indication Anemia due to CKD CKD on dialysis: starting dose 0.45 Dosing Regimen mcg/kg IV or SC weekly, or 0.75 mcg/kg IV or SC every 2 weeks. IV recommended for patients on hemodialysis
    CKD not on dialysis: starting dose 0.45 mcg/kg IV or SC at 4 week intervals
    Maximum Dose Varies depending on indication and frequency of administration. Pediatric patients with CKD: starting dose 0.45 mcg/kg IV or SC weekly;
    patients with CKD not on dialysis may also be initiated at 0.75 mcg/kg every 2 weeks
    Starting dose: 2.25 mcg/kg SC weekly, or 500 mcg SC every 3 weeks until completion of a chemotherapy course 150-300 mcg SC every other week Anemia due to chemotherapy in patients with cancer Anemia associated with MDS† †Off-label NCCN recommended use 500 mcg every other week VI. Product Availability
    • Single-dose vials for injection: 25 mcg, 40 mcg, 60 mcg, 100 mcg, 200 mcg, 300 mcg • Single dose prefilled syringes for injection: 10 mcg/0.4 mL, 25 mcg/0.42 mL, 40 mcg/0.4 mL, 60 mcg/0.3 mL, 100 mcg/0.5 mL, 150 mcg/0.3 mL, 200 mcg/0.4 mL, 300 mcg/0.6 mL, and 500 mcg/1 mL
    VII.