Anthem Blue Cross California Erythropoiesis Stimulating Agents Form

Overview Coding References Clinical criteria Document history Overview This document addresses recombinant erythropoietin products, also known as erythropoiesis stimulating agents (ESAs): • Aranesp (darbepoetin alfa) • Epogen (epoetin alfa) • Mircera (methoxy polyethylene glycol-epoetin beta) • Procrit (epoetin alfa) • Retacrit (epoetin alfa-epbx) Erythropoietin (EPO) is a hormone naturally produced in the body, primarily by the kidneys, which stimulates the bone marrow to produce red blood cells. ESAs are approved for the treatment of severe anemia in chronic kidney disease (CKD), HIV, cancer, surgery and other indications as applicable. ESAs have black box warnings for an increased risk of death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access, and tumor progression or recurrence. For CKD: In controlled trials, individuals experienced greater risks for death, serious adverse cardiovascular reactions and stroke when ESAs were administered to target a hemoglobin (Hgb) level greater than 11 g/dL. Use the lowest dose needed to reduce the need for red blood cell (RBC) transfusions. For Cancer: In controlled trials, ESAs shortened overall survival and/or increased the risk for tumor progression or recurrence in individuals with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers. Use the lowest dose needed to avoid RBC transfusions. Use ESAs only for anemia from myelosuppressive chemotherapy when the anticipated outcome is not cure and discontinue ESAs following completion of a chemotherapy course. Per specialty committee consensus opinion in 4Q21, ongoing treatment with Aranesp or epoetin alfa agents may be used to maintain a hemoglobin level of no greater than 11g/dL in individuals using for myelosuppressive chemotherapy related anemia or myelodysplastic syndrome due to the risk vs. benefit ratio with higher hemoglobin targets. For Perisurgery: Deep venous thrombosis (DVT) prophylaxis is recommended due to increased risk for DVTs. ESAs are contraindicated in individuals with uncontrolled hypertension. Blood pressure should be adequately controlled prior to initiation and during treatment with ESAs. Clinical Criteria When a drug is being reviewed for coverage under a member’s medical benefit plan or is otherwise subject to clinical review (including prior authorization), the following criteria will be used to determine whether the drug meets any applicable medical necessity requirements for the intended/prescribed purpose. Aranesp (darbepoetin alfa) Initial requests for Aranesp (darbepoetin alfa) may be approved if the following criteria are met: 1 I. II. Individual has a baseline hemoglobin (Hgb) level less than 10 g/dL; AND Baseline iron status is adequate as defined by one of the following: A. Transferrin saturation 20% or greater; OR B. Ferritin 80 ng/mL or greater; OR C. Bone marrow demonstrates adequate iron stores; AND III. Individual is using for one of the following: A. Anemia associated with chronic kidney disease (CKD), for individuals on dialysis, to achieve and maintain Hgb levels within the range of 10 to 11 g/dL; OR B. Anemia associated with CKD, for individuals not on dialysis, to achieve and maintain Hgb levels of 10 g/dL; OR C. Myelosuppressive chemotherapy when the following are met: 1. Chemotherapy is planned for a minimum of 2 months; AND 2. Individual has a diagnosis of non-myeloid cancer and the anticipated outcome is not cure; OR D. Myelodysplastic syndrome with an endogenous erythropoietin level less than or equal to 500 mU/mL (NCCN 2A); OR E. Myelofibrosis-associated anemia with an endogenous erythropoietin level less than 500 mU/mL (NCCN 2A). Continuation requests for Aranesp (darbepoetin alfa) may be approved if the following criteria are met: I. II. III. Individual demonstrates continued need for ESA treatment and has confirmation of response to treatment as evidenced by an increase in hemoglobin levels from baseline (i.e., increase of approximately 1 g/dL or greater from baseline); AND Individual is using the lowest ESA dose necessary to avoid transfusions; AND Individual meets one of the following criteria: A. Hemoglobin level is not greater than 11 g/dL for CKD individuals on dialysis, or greater than 10 g/dL for CKD non-dialysis, unless otherwise specified (for example, pediatric individuals with CKD where target Hgb levels is within the range of 10 to 12 g/dL); OR B. Hemoglobin level is not greater than 11 g/dL for individuals using for myelosuppressive chemotherapy related anemia or myelodysplastic syndrome; AND IV. If using for myelosuppressive chemotherapy-related anemia, individual is not using beyond 6 weeks after chemotherapy has completed. Aranesp (darbepoetin alfa) may not be approved for the following: I. II. III. IV. V. VI. VII. VIII. Continued use when the hemoglobin level exceeds 11 g/dL unless otherwise specified (for example, pediatric individuals with CKD where target Hgb levels within the range of 10 to 12 g/dL); Individuals with uncontrolled hypertension; Use beyond 12 weeks of continuous treatment at therapeutic doses in the absence of response in individuals with chronic kidney disease; Use beyond 8 weeks of continuous treatment at therapeutic doses in the absence of response in individuals with myelodysplastic syndrome (MDS); Use beyond 8 weeks of continuous treatment at therapeutic doses in the absence of response or if transfusions are still required in individuals with metastatic, non-myeloid cancer being treated with myelosuppressive chemotherapy agents known to produce anemia; As treatment in the presence of a sudden loss of response with severe anemia and a low reticulocyte count; To treat anemia in individuals with cancer receiving myelosuppressive chemotherapy in whom the anemia can be managed by transfusion; Continued use beyond 6 weeks after therapy with myelosuppressive chemotherapy known to produce anemia is completed. Epogen, Procrit (epoetin alfa); Procrit (epoetin alfa); Retacrit (epoetin alfa-epbx) Initial requests for Epogen (epoetin alfa), Procrit (epoetin alfa), or Retacrit (epoetin alfa-epbx) may be approved if the following criteria are met: I. II. Individual has a baseline hemoglobin (Hgb) level less than 10 g/dL; AND Baseline iron status is adequate as defined by one of the following: 2 A. Transferrin saturation 20% or greater; OR B. Ferritin 80 ng/mL or greater; OR C. Bone marrow demonstrates adequate iron stores; AND III. Individual is using for one of the following: A. Anemia associated with chronic kidney disease (CKD), for individuals on dialysis, to achieve and maintain Hgb levels within the range of 10 to 11 g/dL; OR B. Anemia associated with CKD, for individuals not on dialysis, to achieve and maintain Hgb levels of 10 g/dL; OR C. Myelosuppressive chemotherapy when the following are met: 1. Chemotherapy is planned for a minimum of 2 months; AND 2. Individual has a diagnosis of non-myeloid cancer and the anticipated outcome is not cure; OR D. Myelodysplastic syndrome with an endogenous erythropoietin level less than or equal to 500 mU/mL (NCCN 2A); OR HIV infection, receiving zidovudine at a dose less than or equal to 4200 mg/week, with an endogenous erythropoietin level less than or equal to 500 mU/mL; OR E. Myelofibrosis-associated anemia with an endogenous erythropoietin level less than 500 mU/mL (NCCN 2A). Continuation requests for Epogen (epoetin alfa), Procrit (epoetin alfa), or Retacrit (epoetin alfa-epbx) may be approved if the following criteria are met: I. II. III. Individual demonstrates continued need for ESA treatment and has confirmation of response to treatment as evidenced by an increase in hemoglobin levels from baseline (i.e., increase of approximately 1 g/dL or greater from baseline); AND Individual is using the lowest ESA dose necessary to avoid transfusions; AND Individual meets one of the following criteria: A. Hemoglobin level is not greater than 11 g/dL for CKD individuals on dialysis, or greater than 10 g/dL for CKD non-dialysis, unless otherwise specified (for example, pediatric individuals with CKD where target Hgb levels is within the range of 10 to 12 g/dL); OR B. Hemoglobin level is not greater than 11 g/dL for individuals using for myelosuppressive chemotherapy related anemia or myelodysplastic syndrome; OR C. Hemoglobin level is not greater than 12 g/dL for zidovudine-related anemia in patients with HIV (Label); AND IV. If using for myelosuppressive chemotherapy-related anemia, individual is not using beyond 6 weeks after chemotherapy has completed. Initial and continuation requests for Epogen (epoetin alfa), Procrit (epoetin alfa), or Retacrit (epoetin alfa-epbx) may also be approved if the following criteria are met: I. Individual is undergoing elective, non-cardiac, non-vascular surgery and requires Epogen, Procrit (epoetin alfa), or Retacrit (epoetin alfa-epbx) to reduce the need for allogenic blood transfusions; AND A. Baseline Hgb level is greater than 10 g/dL and less than or equal to 13 g/dL; AND B. C. Baseline iron status is adequate as defined by one of the following: Individual is at high risk for perioperative transfusions with significant, anticipated blood loss; AND 1. Transferrin saturation 20% or greater; OR 2. Ferritin 80 ng/mL or greater; OR 3. Bone marrow demonstrates adequate iron stores. Epogen (epoetin alfa), Procrit (epoetin alfa), or Retacrit (epoetin alfa-epbx) may not be approved for the following: I. II. III. IV. Continued use when the hemoglobin level exceeds 11 g/dL unless otherwise specified (for example, pediatric individuals with CKD where target Hgb levels within the range of 10 to 12 g/dL); Individuals with uncontrolled hypertension; Use beyond 12 weeks of continuous treatment at therapeutic doses in the absence of response in individuals with chronic kidney disease; Use beyond 8 weeks of continuous treatment at therapeutic doses in the absence of response in individuals with myelodysplastic syndrome (MDS); 3 V. VI. VII. VIII. Use beyond 8 weeks of continuous treatment at therapeutic doses in the absence of response or if transfusions are still required in individuals with metastatic, non-myeloid cancer being treated with myelosuppressive chemotherapy agents known to produce anemia; As treatment in the presence of a sudden loss of response with severe anemia and a low reticulocyte count; To treat anemia in individuals with cancer receiving myelosuppressive chemotherapy in whom the anemia can be managed by transfusion; Continued use beyond 6 weeks after therapy with myelosuppressive chemotherapy known to produce anemia is completed. Mircera (methoxy polyethylene glycol-epoetin beta) Initial requests for Mircera (methoxy polyethylene glycol-epoetin beta) may be approved if the following criteria are met: I. II. Individual has a baseline hemoglobin (Hgb) level less than 10 g/dL; AND Baseline iron status is adequate as defined by one of the following: A. Transferrin saturation 20% or greater; OR B. Ferritin 80 ng/mL or greater; OR C. Bone marrow demonstrates adequate iron stores; AND III. Individual is using for one of the following: A. Anemia associated with chronic kidney disease (CKD), for individuals on dialysis, to achieve and maintain Hgb levels within the range of 10 to 11 g/dL; OR B. Anemia associated with CKD, for individuals not on dialysis, to achieve and maintain Hgb levels of 10 g/dL. Continuation requests for Mircera (methoxy polyethylene glycol-epoetin beta) may be approved if the following criteria are met: I. II. III. Individual demonstrates continued need for ESA treatment and has confirmation of response to treatment as evidenced by an increase in hemoglobin levels from baseline (i.e., increase of approximately 1 g/dL or greater from baseline); AND Individual is using the lowest ESA dose necessary to avoid transfusions; AND Hemoglobin level is not greater than 11 g/dL for CKD individuals on dialysis, or greater than 10 g/dL for CKD non-dialysis, unless otherwise specified. Mircera (methoxy polyethylene glycol-epoetin beta) may not be approved for the following: I. II. III. IV. Continued use when the hemoglobin level exceeds 11 g/dL unless otherwise specified; Individuals with uncontrolled hypertension; Use beyond 12 weeks of continuous treatment at therapeutic doses in the absence of response in individuals with chronic kidney disease; As treatment in the presence of a sudden loss of response with severe anemia and a low reticulocyte count. Approval Duration for Erythropoiesis Stimulating Agents (dialysis-dependent use excluded) Initial Requests: 6 months Continuation Requests: 6 months Step Therapy Summary of FDA-Approved Indications or Indications Meeting Off-Label Use Policy for Erythropoiesis Stimulating Agents (ESAs): Agent Anemia due to CKD Anemia due to zidovudine in HIV infection Anemia due to myelosuppressive chemotherapy Reduction of allogenic RBC transfusions in individuals Aranesp X Epogen X Mircera X Procrit X Retacrit X X X X X X X X X X X 4 undergoing elective, non-cardiac, non-vascular surgery Myelodysplastic syndrome† † Off-label use X X X X Note: When an erythropoiesis stimulating agent (ESA) is deemed approvable based on the clinical criteria above, the benefit plan may have additional criteria requiring the use of a preferred1 agent or agents. Non-Preferred Erythropoiesis Stimulating Agents (ESAs) Step Therapy A list of the preferred erythropoiesis stimulating agents is available here. In the presence of a drug shortage of the preferred product, the non-preferred product may be approved. Requests for a non-preferred erythropoiesis stimulating agent (ESA) may be approved if the following criteria are met: I. If designated, individual has had a trial and inadequate response or intolerance to one preferred ESA; OR II. OR III. OR IV. The preferred agent is not FDA-approved and does not have an accepted off-label use per the off-label policy for the prescribed indication and the requested non-preferred agent does; If Epogen (epoetin alfa), Procrit (epoetin alfa), or Retacrit (epoetin alfa-epbx) are designated as non- preferred agents, either may be approved if individual is requesting for anemia associated with one of the following: A. Chronic kidney disease and between 1 month and less than 12 months of age; OR B. Myelosuppressive chemotherapy and between 5 years and less than 18 years of age; Individual is dialysis-dependent and using in conjunction with dialysis. 1Preferred, as used herein, refers to agents that were deemed to be clinically comparable to other agents in the same class or disease category but are preferred based upon clinical evidence and cost effectiveness. Quantity Limits Erythropoiesis Stimulating Agents Quantity Limits Aranesp (darbepoetin alfa) 10 mcg/0.4 mL, 40 mcg/0.4 mL, 200 mcg/0.4 mL Syringe Aranesp (darbepoetin alfa) 25 mcg/0.42 mL Syringe Drug Aranesp (darbepoetin alfa) 60 mcg/0.3 mL, 150 mcg/0.3 mL Syringe Aranesp (darbepoetin alfa) 100 mcg/0.5 mL Syringe Aranesp (darbepoetin alfa) 300 mcg/0.6 mL Syringe Aranesp (darbepoetin alfa) 500 mcg/mL Syringe Aranesp (darbepoetin alfa) 25 mcg/mL, 40 mcg/mL, 60 mcg/mL, 100 mcg/mL, 200 mcg/mL, 300 mcg/mL Vial Epogen (epoetin alfa) 2,000 Units/mL; 3,000 Units/mL; 4,000 Units/mL; 10,000 Units/mL Vial; 20,000 Units/mL Vial * Epogen (epoetin alfa) 20,000 Units/2 mL Multi-Dose Vial* Mircera (methoxy polyethylene glycol-epoetin beta) 30 mcg/0.3mL, 50 mcg/0.3 mL, 75 mcg/0.3 mL, 100 mcg/0.3 mL, 120 mcg/0.3 mL, 150 mcg/0.3 mL, 200 mcg/0.3 mL Syringe Procrit (epoetin alfa) 2,000 Units/mL; 3,000 Units/mL; 4,000 Units/mL; 10,000 Units/mL; 20,000 Units/mL; 40,000 Units/mL Vial** Limit 4 syringes (1.6 mL) per 28 days 4 syringes (1.68 mL) per 28 days 4 syringes (1.2 mL) per 28 days 4 syringes (2 mL) per 28 days 4 syringes (2.4 mL) per 28 days 4 syringes (4 mL) per 28 days 4 vials (4 mL) per 28 days 12 vials (12 mL) per 28 days 6 vials (12 mL) per 28 days 2 syringes (0.6 mL) per 28 days 12 vials (12 mL) per 28 days 5 Procrit (epoetin alfa) 20,000 Units/2 mL Multi-Dose Vial** Retacrit (epoetin alfa-epbx) 2,000 Units/mL; 3,000 Units/mL; 4,000 Units/mL; 10,000 Units/mL; 20,000 Units/mL, 40,000 Units/mL Vialǂ Retacrit (epoetin alfa-epbx) 20,000 Units/2 mL Multi-Dose Vialǂ 6 vials (12 mL) per 28 days 12 vials (12 mL) per 28 days 6 vials (12 mL) per 28 days *When Epogen (epoetin alfa) is being used to reduce the need for allogeneic red blood cell transfusions in elective, noncardiac, nonvascular surgery, may allow up to an additional 3 vials (2,000 Units/mL; 3,000 Units/mL; 4,000 Units/mL; 10,000 Units/mL; 20,000 Units/mL; 20,000 Units/2 mL) in a rolling 28 days for completion of therapy. Override Criteria **When Procrit (epoetin alfa) is being used to reduce the need for allogeneic red blood cell transfusions in elective, noncardiac, nonvascular surgery, may allow up to an additional 3 vials (2,000 Units/mL; 3,000 Units/mL; 4,000 Units/mL; 10,000 Units/mL; 20,000 Units/mL; 20,000 Units/2 mL; 40,000 Units/mL) in a rolling 28 days for completion of therapy. ǂWhen Retacrit (epoetin alfa-epbx) is being used to reduce the need for allogeneic red blood cell transfusions in elective, noncardiac, nonvascular surgery, may allow up to an additional 3 vials (2,000 Units/mL; 3,000 Units/mL; 4,000 Units/mL; 10,000 Units/mL; 40,000 Units/mL) in a rolling 28 days for completion of therapy. Coding The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member’s contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member. HCPCS J0881 J0882 J0885 J0887 J0888 Q4081 Q5105 Q5106 EA EB EC Injection, darbepoetin alfa, 1 mcg (non-ESRD use) Injection, darbepoetin alfa, 1 mcg (for ESRD on dialysis) Injection, epoetin alfa (for non-ESRD use), 1000 units [Epogen, Procrit] Injection, epoetin beta, 1 microgram, (for ESRD on dialysis) [Mircera] Injection, epoetin beta, 1 microgram, (for non-ESRD use) [Mircera] Injection, epoetin alfa, 100 units (for ESRD on dialysis) [Epogen, Procrit] Injection, epoetin alfa, biosimilar, (Retacrit) (for esrd on dialysis), 100 units Injection, epoetin alfa, biosimilar, (Retacrit) (for non-esrd use), 1000 units Erythropoetic stimulating agent (ESA) administered to treat anemia due to anti-cancer chemotherapy Erythropoetic stimulating agent (ESA) administered to treat anemia due to anti-cancer radiotherapy Erythropoetic stimulating agent (ESA) administered to treat anemia not due to anti-cancer radiotherapy or anti-cancer chemotherapy ICD-10 Diagnosis D63.1 D62.81 D75.81 I12.0 N18.1-N18.5 Anemia in chronic kidney disease Myelophthisic anemia Myelofibrosis Hypertensive chronic kidney disease with stage 5 chronic kidney disease or end stage renal disease Chronic kidney disease (CKD) Stages I-V N18.6 End state renal disease Document History 6 Revised: 08/18/2023