262 Form

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Pharmacy Medical Policy Erythropoietin, Recombinant Human and hypoxia-inducible factor inhibitors Table of Contents • Related Polices

• Prior Authorization Information

• Summary • Policy

• Provider Documentation

• Individual Consideration • CPT /HCPCS / ICD Codes

• Policy History

• Forms

• References Policy Number: 262 BCBSA Reference Number: N/A Related Policies • Quality Care Dosing guidelines may apply to the following medications and can be found in Medical Policy #621A.

Prior Authorization Information Policy ☒ Prior Authorization ☐ Step Therapy ☒ Quantity Limit ☐ Administrative Reviewing Department Pharmacy Operations: Tel: 1-800-366-7778 Fax: 1-800-583-6289 Policy Effective Date 11/2024 Pharmacy (Rx) or Medical (MED) benefit coverage ☒ Rx ☐ MED To request for coverage: Providers may call, fax, or mail the attached form (Formulary Exception/Prior Authorization form) to the address below.
Blue Cross Blue Shield of Massachusetts Pharmacy Operations Department 25 Technology Place Hingham, MA 02043
Tel: 1-800-366-7778 Fax: 1-800-583-6289

Individual Consideration for the atypical patient: Policy for requests that do not meet clinical criteria of this policy, see section labeled Individual Consideration
Policy applies to Commercial Members:
• Managed Care (HMO and POS),
• PPO and Indemnity • MEDEX with Rx plan • Managed Major Medical with Custom BCBSMA Formulary • Comprehensive Managed Major Medical with Custom BCBSMA Formulary • Managed Blue for Seniors with Custom BCBSMA Formulary Policy does NOT apply to: • Medicare Advantage

Summary This is a comprehensive policy covering prior authorization and quantity limit requirements for Erythropoiesis-Stimulating Agent (ESA) and hypoxia-inducible factor inhibitors used for the treatment of anemias.

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Formulary status/requirements for Erythropoiesis-Stimulating Agents is as follows
Drug Formulary Status (BCBSMA Commercial Plan) Requirement Special Considerations Preferred Retacrit ™ (epoetin alfa-epbx) Covered, PA, QCD PA required. See below for criteria.

*SPBO - Covered under Pharmacy benefit only (see other information section) – Does not apply to emergency room, inpatient, ambulatory surgery center or home infusion
Current Hemoglobin levels are required prior to dispensing.

Non-preferred

Aranesp ® (darbepoetin alfa) NFNC, PA, QCD PA required. See below for criteria.
Requires treatment failure with Retacrit Epogen ® (erythropoietin) NFNC, PA, QCD Jesduvroq ™ (daprodustat) NFNC, PA, QCD Procrit ® (erythropoietin) NFNC, PA, QCD* Vafseo ®(vadadustat) NFNC, PA, QCD QCD - Quality Care Dosing (quantity limits policy #621B); SPBO – Specialty Pharmacy benefit only coverage; PA – Prior Authorization required; ST – Step Therapy; NFNC – Non-formulary / Non-covered Policy Length of Approval 1 - 6 months Formulary Status All requests must meet the Prior Authorizations requirement. For non-covered medications, the member must also have had a previous treatment failure with, or contraindication to, at least two covered formulary alternatives when available. See section on individual consideration for more information if you require an exception to any of these criteria requirements for an atypical patient.
Member cost share consideration A higher non-preferred cost share may be applied if an exception request is approved for coverage of a non-preferred or a non-formulary/non-covered drug. Prior Authorization Criteria
For medications dispensed under the retail pharmacy benefit, current hemoglobin levels will be required upon request by the specialty pharmacy prior to each dispense. NOTE: Hemoglobin (Hb) levels must be actual lab values from within the previous seven days and not target levels.
Retacrit, Epogen, and Procrit Retacrit may be considered MEDICALLY NECESSARY for treatment of the following indications when ALL of the corresponding criteria are met (Note: Epogen, and Procrit may be covered only AFTER treatment failure of Retacrit when the corresponding criteria are met):

1. Anemia of chronic renal failure6 – defined as GFR ≤ 60 mL/min/1.73m2 for at least 3 months or patients on dialysis16 a. Initiation: Approve x 6 months if Hb ≤ 11.0 g/dL b. Continuation: Approve x 6 months if Hb ≤ 12.0 g/dL

2. Anemia due to AZT treatment in AIDS a. Initiation: Approve x 6 months if Hb ≤ 10.0 g/dL or endogenous erythropoietin levels ≤ 500mUnits/mL

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b. Continuation: Approve x 6 months if Hb ≤ 12.0g/dL

3. Anemia due to Ribavirin therapy in the treatment of Hepatitis C9,10,11, 25 a. Initiation: Approve x 6 months if Hb ≤ 10.0 g/dL b. Continuation: Approve x 6 months is Hb ≤ 12.0g/dL

4. Myelodysplastic syndromes1 confirmed by bone marrow biopsy and/or aspirate23 a. Initiation: Approve x 6 months if Hb ≤ 12.0 g/dL b. Continuation: Approve x 6 months if Hb ≤ 12.0 g/dL

5. Anemia due to the effects of concurrently administered chemotherapy in patients with non- myeloid malignancies2,4,18,19
   a. Initiation: Approve x 6 months if Hb ≤ 10.0 g/dL OR Hb > 10.0 g/dL but ≤12 g/dL and the physician anticipates a Hb decrease OR the patient has comorbidities that require higher Hb levels b. Continuation: Approve x 6 months if Hb ≤ 12.0 g/dL

6. Anemia following allogeneic bone marrow transplant1,4
   a. Initiation: Approve x 6 months if Hb ≤ 10.0 g/dL b. Continuation: Approve x 6 months is Hb ≤ 12.0g/dL

7. Anemic surgical patients who meet ALL the following: a. The surgery is elective, non-cardiac, and non-vascular; AND b. Hemoglobin levels are between 10 and 13 g/d; AND c. Not willing to donate blood. Approve x 1 month of therapy Aranesp Aranesp ® may be covered after treatment failure of Retacrit ™ for the below indications only and when the corresponding criteria are met:

8. Anemia associated with chronic renal failure7,15 defined as GFR ≤ 60 mL/min/1.73m2 for at least 3 months or patients on dialysis a. Initiation: Approve x 6 months if Hb ≤ 11.0 g/dL b. Continuation: Approve x 6 months if Hb ≤ 12.0 g/dL

9. Anemia due to the effects of concurrently administered chemotherapy in patients with non- myeloid malignancies8,18,19 a. Initiation: Approve x 6 months if Hb ≤ 10.0 g/dL OR Hb > 10.0 g/dL but ≤12 g/dL and the physician anticipates a Hb decrease OR the patient has comorbidities that require higher Hb levels b. Continuation: Approve x 6 months if Hb ≤ 12.0 g/dL

   Jesduvroq, Vafseo Jesduvroq ™ (daprodustat) or Vafseo (vadadustat) may be covered after treatment failure of Retacrit ™ for the below indications only and when the corresponding criteria are met:

10. Anemia associated with chronic renal failure7,15 defined as GFR ≤ 60 mL/min/1.73m2 for at least 3 months and the patient is on dialysis: a. Initiation: Approve x 6 months if Hb ≤ 11.0 g/dL b. Continuation: Approve x 6 months if Hb ≤ 11.0 g/dL

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Non-Covered Indications We do NOT cover Epoetin alpha or Darbepoetin alpha to treat other anemias, including the following, because there is inadequate published evidence to show that health outcomes (such as decreased need for transfusions) are improved:

1. Anemia due to hemolysis, nutritional deficiencies, GI bleeds, and other GI problems2
2. Iron deficiency anemia: It is known that patients with iron deficiency do not respond as well to epoetin alpha or darbepoetin alpha, therefore these drugs are not covered for patients whose transferrin saturation is less than 20%2

3. Anemia due to cancer in patients not receiving cancer chemotherapy Other Information Blue Cross Blue Shield of Massachusetts (BCBSMA*) members (other than Medex®; Blue MedicareRx, Medicare Advantage plans that include prescription drug coverage) will be required to fill their prescriptions for the above medications at one of the providers in our retail specialty pharmacy network, as listed below:

   Retail Specialty Pharmacy Contact Information: AcariaHealth. Phone:1-866-892-1202 Fax: 1-866-892-3223

   Website: www.acariahealth.com Accredo Health Group Phone: 1-877-988-0058 Fax: 1-866-489-1907

   Website: www.accredo.com AllCare Plus Pharmacy Phone: 1-855-880-1091 Fax: 1-844-265-0265

   Website: www.allcarepluspharmacy.com Caremark, Inc. Phone: 1-866-846-3096 Fax: 1-800-323-2445

   Website: www.caremark.com Onco360, the Oncology Pharmacy Phone: 1-877-662-6633 Fax: 1-877-662-6355

   Website: www.onco360.com AllianceRx Walgreens Prime Phone: 1-800-649-2872 Fax: 1-866-935-0719

   Website: https://alliancerxwp.com

   Clinical Trials for Cancer Mandate As required by law, we provide coverage for services and supplies received as part of a qualified clinical trial (for treatment of cancer) when the member is enrolled in that trial. This coverage is provided for services

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and supplies that are consistent with the study protocol and with the standard of care for someone with the patients’ diagnosis, and that would be covered if the patient did not participate in the trials. This coverage may also be provided for investigational drugs and devices that have been approved for use as part of the trial. Coverage for services and supplies that are received as part of a qualified clinical trial is provided to the same extent as it would have been provided if the patient did not participate in the trial.

However, no coverage is provided for: • Investigational drugs and devices that have not been approved for use in the trial. • Investigational drugs and devices that are paid for by the manufacturer, distributor or provider of the drug or device, whether or not the drug or device has been approved for use in the trial. • Non-covered services under the member’s contract. • Costs associated with managing the research for the trial. • Items, services or costs that are reimbursed or otherwise furnished by the sponsor of the trial. • Costs of services that are inconsistent with widely accepted and established national and regional standards of care. • Costs of clinical trials that are not “qualified trials.” Provider Documentation Requirements
Documentation from the provider to support a reason preventing trial of formulary alternative(s) must include the name and strength of alternatives tried and failed (if alternatives were tried, including dates if available) and specifics regarding the treatment failure. Documentation to support clinical basis preventing switch to formulary alternative should also provide specifics around clinical reason.
Individual Consideration (For Atypical Patients) Our medical policies are written for most people with a given condition. Each policy is based on peer reviewed clinical evidence. We also take into consideration the needs of atypical patient populations and diagnoses.
If the coverage criteria outlined is unlikely to be clinically effective for the prescribed purpose, the health care provider may request an exception to cover the requested medication based on an individual’s unique clinical circumstances. This is also referred to as “individual consideration” or an “exception request.”
Some reasons why you may need us to make an exception include: therapeutic contraindications; history of adverse effects; expected to be ineffective or likely to cause harm (physical, mental, or adverse reaction).
To facilitate a thorough and prompt review of an exception request, we encourage the provider to include additional supporting clinical documentation with their request. This may include: • Clinical notes or supporting clinical statements; • The name and strength of formulary alternatives tried and failed (if alternatives were tried) and specifics regarding the treatment failure, if applicable; • Clinical literature from reputable peer reviewed journals; • References from nationally recognized and approved drug compendia such as American Hospital Formulary Service® Drug Information (AHFS-DI), Lexi-Drug, Clinical Pharmacology, Micromedex or Drugdex®; and • References from consensus documents and/or nationally sanctioned guidelines.

Providers may call, fax or mail relevant clinical information, including clinical references for individual patient consideration, to:

Blue Cross Blue Shield of Massachusetts Pharmacy Operations Department 25 Technology Place Hingham, MA 02043
Phone: 1-800-366-7778 Fax: 1-800-583-6289

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We may also use prescription claims records to establish prior use of formulary alternatives or to show if step therapy criteria has been met. We will require the provider to share additional information when prescription claims data is either not available or the medication fill history fails to establish use of preferred formulary medications or that step therapy criteria has been met.

CPT Codes / HCPCS Codes / ICD Codes

The following codes are included below for informational purposes. Inclusion or exclusion of a code does not constitute or imply member coverage or provider reimbursement. Please refer to the member’s contract benefits in effect at the time of service to determine coverage or non-coverage as it applies to an individual member.

Providers should report all services using the most up-to-date industry-standard procedure, revenue, and diagnosis codes, including modifiers where applicable.

The following codes are included below for informational purposes only; this is not an all-inclusive list.

The above medical necessity criteria MUST be met for the following codes to be covered for Commercial Members: Managed Care (HMO and POS), PPO, and Indemnity:

HCPCS Codes HCPCS codes: Code Description J0881 Injection, darbepoetin alfa, 1 mcg (non-ESRD use) [Arenesp] J0882 Injection, darbepoetin alfa, 1 mcg (for ESRD on dialysis) [Arenesp] J0885 Injection, epoetin alfa, (for non-ESRD use), 1000 units [Epogen, Procrit] Q4081 Injection, epoetin alfa, 100 units (for ESRD on dialysis) [Epogen, Procrit] Q5105 Injection, epoetin alfa, biosimilar, (retacrit) (for esrd on dialysis), 100 units Q5106 Injection, epoetin alfa, biosimilar, (retacrit) (for non-esrd use), 1000 units

The following ICD Diagnosis Codes are considered medically necessary when submitted with the HCPCS codes above if medical necessity criteria are met: ICD-10 Diagnosis Codes ICD-10-CM diagnosis codes: Code Description D46.0 Refractory anemia without ring sideroblasts, so stated D46.1 Refractory anemia with ring sideroblasts D46.20 Refractory anemia with excess of blasts, unspecified D46.21 Refractory anemia with excess of blasts 1 D46.22 Refractory anemia with excess of blasts 2 D46.4 Refractory anemia, unspecified D46.9 Myelodysplastic syndrome, unspecified D46.A Refractory cytopenia with multilineage dysplasia D46.B Refractory cytopenia with multilineage dysplasia and ring sideroblasts D46.C Myelodysplastic syndrome with isolated del(5q) chromosomal abnormality D46.Z Other myelodysplastic syndromes D61.1 Drug-induced aplastic anemia D61.2 Aplastic anemia due to other external agents D61.3 Idiopathic aplastic anemia D61.89 Other specified aplastic anemias and other bone marrow failure syndromes D61.9 Aplastic anemia, unspecified

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D63.0 Anemia in neoplastic disease D63.1 Anemia in chronic kidney disease D63.8 Anemia in other chronic diseases classified elsewhere D64.4 Congenital dyserythropoietic anemia D64.81 Anemia due to antineoplastic chemotherapy D64.89 Other specified anemias D64.9 Anemia, unspecified N18.1 Chronic kidney disease, stage 1 N18.2 Chronic kidney disease, stage 2 (mild) N18.30 Chronic kidney disease, stage 3 unspecified N18.31 Chronic kidney disease, stage 3a N18.32 Chronic kidney disease, stage 3b N18.4 Chronic kidney disease, stage 4 (severe) N18.5 Chronic kidney disease, stage 5 N18.6 End stage renal disease N18.9 Chronic kidney disease, unspecified

Effective 7/1/08: One of the following modifier codes must accompany the drug HCPCS code on the CMS 1500 form in order for the claim to adjudicate. ED - Hematocrit level has exceeded 39% (or hemoglobin level has exceeded 13.0 g/dL) for 3 or more consecutive billing cycles immediately prior to and including the current cycle.
EE – Hematocrit level has not exceeded 39% (or hemoglobin level has not exceeded 13.0 g/dL) for 3 or more consecutive billing cycle immediately prior to and including the current cycle.
**PLEASE NOTE: These coding modifiers do not apply to the Federal Employee Program (FEP), the BlueCard® Program (BCBSBMA members), or to plans in which Medicare is the primary insurer (e.g. Medicare Advantage, Medex®, or Managed Blue for Seniors™).

For end stage renal disease (ESRD) patients only: • The initial claim must contain the following information: o patient’s diagnosis o most recent creatinine prior to starting on erythropoietin o most recent hematocrit prior to starting on erythropoietin o most recent transferrin saturation o dosage in units/kilograms o patients weight in kilograms o number of units of erythropoietin administered o Subsequent claims must contain: ▪ patient’s diagnosis ▪ hematocrit ▪ number of units administered • We do not separately reimburse the administration of the drug () when done in conjunction with an office visit. Policy History Date Action 11/2024 Updated to add Vafseo® to the policy under medical only. 1/2024 Updated to add Jesduvroq ™ to the policy under medical only. 11/2023 Reformatted Policy. 10/2023 Reformatted Policy and updated IC to align with 118E MGL § 51A. 7/2023 Reformatted Policy. 8/2022 Updated to remove peginesatide from the policy. 12/2021 BCBSA National medical policy review. No changes to policy statements. New references added. 12/2020 BCBSA National medical policy review. No changes to policy statements. New references added. 10/2020 Clarified coding information and Removed deleted code

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7/2019 Updated to add Procrit to non-covered and to update criteria for Retacrit preferred.
11/2018 BCBSA National medical policy review. No changes to policy statements. New references added. 11/2018 Updated to co-prefer Retacrit & Procrit. 7/2018 Updated to include new to market Retacrit. 10/2017 Updated to change Walgreens Specialty Name. 7/2017 Updated to add AllCare to Pharmacy Specialty list. 6/2017 Updated address for Pharmacy Operations. 5/2017 Updated to clarify Epoetin alpha criteria. 1/2016 Updated to add NC designation to Epogen & Aranesp. 8/2015 Updated to add Pharmacy Benefit only Program designation. 7/2015 Updated to add Walgreens Specialty. 7/2014 Updated Coding section with ICD10 procedure and diagnosis codes, effective 10/2015. 2/2014 Updated Onco360 name and removed Curascript in Specialty Pharmacy section. 1/2014 Updated ExpressPAth Language and removed Blue Value. 1/2013 Updated 1/2013 to include coverage criteria for new FDA approved medication Omontys®. 4/2012 Updated with specialty pharmacy contact information. 11/2011-4/2012 Medical policy ICD 10 remediation: Formatting, editing and coding updates.
No changes to policy statements.
10/2011 Reviewed - Medical Policy Group - Gastroenterology, Nutrition and Organ Transplantation. No changes to policy statements. 1/2011 Updated to define diagnosis criteria, authorization timeframes and hemoglobin level requirements.
11/2010 Reviewed - Medical Policy Group - Gastroenterology, Nutrition and Organ Transplantation. No changes to policy statements. 9/2010 Reviewed - Medical Policy Group - Hematology and Oncology. No changes to policy statements. 4/2010 Updated to include updated Specialty Retail Pharmacy contact and 4/1/2010 transition information. 11/2009 Reviewed - Medical Policy Group - Gastroenterology, Nutrition and Organ Transplantation. No changes to policy statements. 9/2009 Reviewed - Medical Policy Group - Hematology and Oncology. No changes to policy statements. 10/2009 Updated to remove Medicare Part D criteria and update UM requirements.
8/7/2009 Updated to add Q code for epoetin alpha on dialysis as requested, formatting updated.
11/2008 Reviewed - Medical Policy Group - Gastroenterology, Nutrition and Organ Transplantation. No changes to policy statements. 11/2008 Updated to clarify claim submission requirements and update of ICD-9 code.
10/2008 Reviewed - Medical Policy Group - Hematology and Oncology. No changes to policy statements. 7/2008 Updated to include applicable ICD-9 diagnosis codes, addition of specialty pharmacy vendor OTN Specialty Services and to include modifier codes for physician billing submission.
9/2007 Reviewed - Medical Policy Group - Hematology and Oncology. No changes to policy statements. 6/2007 Reviewed - Medical Policy Group - Urology and Obstetrics/Gynecology. No changes to policy statements. 6/2007 Updated to include retail pharmacy specialty network information, addition of criteria for target hemoglobin ≤ 12 g/dL and removal of “anemia due to cancer” as a covered diagnosis based upon.
10/1989 New policy, issued 10/1989, describing covered and non-covered indications.

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Forms To request prior authorization using the Massachusetts Standard Form for Medication Prior Authorization Requests (eForm), click the link below: https://www.bluecrossma.org/medical-policies/sites/g/files/csphws2091/files/acquiadam- assets/023%20E%20Form%20medication%20prior%20auth%20instruction%20prn.pdf OR Print and fax, Massachusetts Standard Form for Medication Prior Authorization Requests #434

References

1. Food and Drug Administration (FDA). Postmarket Drug Safety Information for Patients and Providers: Information on Erythropoiesis-Stimulating Agents (ESA) Epoetin alfa (marketed as Procrit, Epogen), Darbepoetin alfa (marketed as Aranesp). 2017; https://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm1093 75.htm. Accessed August 14, 2021.
2. Hoffmann-LaRoche. Highlights of Prescribing Information: Mircera (methoxy polyethylene glycol- epoetin beta). 2018; https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125164s078lbl.pdf. Accessed August 14, 2021.
3. Amgen. Highlights of Prescribing Information: Aranesp (darbepoetin alfa). 2019; https://pi.amgen.com/~/media/amgen/repositorysites/pi-amgen- com/aranesp/ckd/aranesppihcp_english.ashx. Accessed August 13, 2021.
4. Amgen. Highlights of Prescribing Information: Epogen (epoetin alfa). 2018; https://pi.amgen.com/~/media/amgen/repositorysites/pi-amgen- com/epogen/epogenpihcp_english.ashx. Accessed August 14, 2021.
5. Janssen. Highlights of Prescribing Information: Procrit (epoetin alfa). 2018; http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/PROCRIT- pi.pdf. Accessed August 14, 2021.
6. Seidenfeld J, Piper M, Bohlius J, et al. Comparative Effectiveness of Epoetin and Darbepoetin for Managing Anemia in Patients Undergoing Cancer Treatment (Comparative Effectiveness Review No. 3). Rockville, MD: Agency for Healthcare Research and Quality; 2006.
7. Bohlius J, Wilson J, Seidenfeld J, et al. Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients. J Natl Cancer Inst. May 17 2006; 98(10): 708-14. PMID 16705125
8. Grant MD, Piper M, Bohlius J, et al. Epoetin and Darbepoetin for Managing Anemia in Patients Undergoing Cancer Treatment: Comparative Effectiveness Update (Comparative Effectiveness Review No. 113). Rockville, MD: Agency for Healthcare Research and Quality; 2013.
9. Bohlius J, Schmidlin K, Brillant C, et al. Erythropoietin or Darbepoetin for patients with cancer--meta- analysis based on individual patient data. Cochrane Database Syst Rev. Jul 08 2009; (3): CD007303. PMID 19588423
10. Bohlius J, Schmidlin K, Brillant C, et al. Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta-analysis of randomised trials. Lancet. May 02 2009; 373(9674): 1532-42. PMID 19410717
11. Tonia T, Mettler A, Robert N, et al. Erythropoietin or darbepoetin for patients with cancer. Cochrane Database Syst Rev. Dec 12 2012; 12: CD003407. PMID 23235597
12. Bohlius J, Bohlke K, Castelli R, et al. Management of Cancer-Associated Anemia With Erythropoiesis- Stimulating Agents: ASCO/ASH Clinical Practice Guideline Update. J Clin Oncol. May 20 2019; 37(15): 1336-1351. PMID 30969847
13. Rizzo JD, Brouwers M, Hurley P, et al. American Society of Clinical Oncology/American Society of Hematology clinical practice guideline update on the use of epoetin and darbepoetin in adult patients with cancer. J Clin Oncol. https://ascopubs.org/doi/full/10.1200/jco.2010.29.2201. Accessed August 14,
15. Food and Drug Administration (FDA) ODAC. FDA Briefing Document: Continuing reassessment of the risks of erythropoiesis-stimulating agents (ESAs) administered for the treatment of anemia associated with cancer chemotherapy. 2007; https://wayback.archive-

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it.org/7993/20170405053529/https://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4301b2-02- FDA.pdf. Accessed August 12, 2021.

15. Centers for Medicare & Medicaid Services (CMS). Decision Memo for Erythropoiesis Stimulating Agents (ESAs) for non-renal disease indications (CAG-00383N). 2007; https://www.cms.gov/medicare- coverage-database/new-search/search- results.aspx?keyword=ESA&keywordType=any&areaId=all&docType=NCA,CAL,NCD,MEDCAC,TA,M CD,6,3,5,1,F,P&contractOption=all&sortBy=relevance. Accessed August 14, 2021.
16. Food and Drug Administration (FDA). FDA Advisory Committee Briefing Document: Joint meeting of the Cardiovascular and Renal Drugs Advisory Committee and the Drug Safety and Risk Management Committee. Reassessment of the risks of erythropoiesis-stimulating agents (ESAs) administered for the treatment of anemia associated with chronic renal failure. 2007; https://wayback.archive- it.org/7993/20170405051117/https://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4315b1-01- FDA.pdf. Accessed August 13, 2021.
17. Strippoli GF, Craig JC, Manno C, et al. Hemoglobin targets for the anemia of chronic kidney disease: a meta-analysis of randomized, controlled trials. J Am Soc Nephrol. Dec 2004; 15(12): 3154-65. PMID 15579519
18. KDOQI. KDOQI Clinical Practice Guideline and Clinical Practice Recommendations for anemia in chronic kidney disease: 2007 update of hemoglobin target. Am J Kidney Dis. Sep 2007; 50(3): 471-
19. PMID 17720528
20. Besarab A, Bolton WK, Browne JK, et al. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med. Aug 27 1998; 339(9): 584-90. PMID 9718377
21. Fishbane S, Besarab A. Mechanism of increased mortality risk with erythropoietin treatment to higher hemoglobin targets. Clin J Am Soc Nephrol. Nov 2007; 2(6): 1274-82. PMID 17942772
22. Singh AK, Szczech L, Tang KL, et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med. Nov 16 2006; 355(20): 2085-98. PMID 17108343
23. Inrig JK, Barnhart HX, Reddan D, et al. Effect of hemoglobin target on progression of kidney disease: a secondary analysis of the CHOIR (Correction of Hemoglobin and Outcomes in Renal Insufficiency) trial. Am J Kidney Dis. Sep 2012; 60(3): 390-401. PMID 22537421
24. Drueke TB, Locatelli F, Clyne N, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med. Nov 16 2006; 355(20): 2071-84. PMID 17108342
25. Pfeffer MA, Burdmann EA, Chen CY, et al. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med. Nov 19 2009; 361(21): 2019-32. PMID 19880844
26. Skali H, Parving HH, Parfrey PS, et al. Stroke in patients with type 2 diabetes mellitus, chronic kidney disease, and anemia treated with Darbepoetin Alfa: the trial to reduce cardiovascular events with Aranesp therapy (TREAT) experience. Circulation. Dec 20 2011; 124(25): 2903-8. PMID 22104547
27. Amato L, Addis A, Saulle R, et al. Comparative efficacy and safety in ESA biosimilars vs. originators in adults with chronic kidney disease: a systematic review and meta-analysis. J Nephrol. Jun 2018; 31(3): 321-332. PMID 28646375
28. Roger SD, Tio M, Park HC, et al. Intravenous iron and erythropoiesis-stimulating agents in haemodialysis: A systematic review and meta-analysis. Nephrology (Carlton). Dec 2017; 22(12): 969-
29. PMID 27699922
30. Cody JD, Hodson EM. Recombinant human erythropoietin versus placebo or no treatment for the anaemia of chronic kidney disease in people not requiring dialysis. Cochrane Database Syst Rev. Jan 20 2016; (1): CD003266. PMID 26790135
31. Collister D, Komenda P, Hiebert B, et al. The Effect of Erythropoietin-Stimulating Agents on Health- Related Quality of Life in Anemia of Chronic Kidney Disease: A Systematic Review and Meta-analysis. Ann Intern Med. Apr 05 2016; 164(7): 472-8. PMID 26881842
32. Palmer SC, Saglimbene V, Craig JC, et al. Darbepoetin for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. Mar 31 2014; (3): CD009297. PMID 24683046
33. Vinhas J, Barreto C, Assuncao J, et al. Treatment of anaemia with erythropoiesis-stimulating agents in patients with chronic kidney disease does not lower mortality and may increase cardiovascular risk: a meta-analysis. Nephron Clin Pract. 2012; 121(3-4): c95-101. PMID 23182871
34. Saglimbene V, Palmer SC, Craig JC, et al. Low versus high dose erythropoiesis-stimulating agents in hemodialysis patients with anemia: A randomized clinical trial. PLoS One. 2017; 12(3): e0172735. PMID 28249030
35. Walker RG, Strippoli GF. A pegylated epoetin in anaemia of renal disease: non-inferiority for an unvalidated surrogate. Lancet. Oct 20 2007; 370(9596): 1395-6. PMID 17950848

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34. Macdougall IC, Walker R, Provenzano R, et al. C.E.R.A. corrects anemia in patients with chronic kidney disease not on dialysis: results of a randomized clinical trial. Clin J Am Soc Nephrol. Mar 2008; 3(2): 337-47. PMID 18287255
35. Klinger M, Arias M, Vargemezis V, et al. Efficacy of intravenous methoxy polyethylene glycol-epoetin beta administered every 2 weeks compared with epoetin administered 3 times weekly in patients treated by hemodialysis or peritoneal dialysis: a randomized trial. Am J Kidney Dis. Dec 2007; 50(6): 989-1000. PMID 18037099
36. Canaud B, Mingardi G, Braun J, et al. Intravenous C.E.R.A. maintains stable haemoglobin levels in patients on dialysis previously treated with darbepoetin alfa: results from STRIATA, a randomized phase III study. Nephrol Dial Transplant. Nov 2008; 23(11): 3654-61. PMID 18586762
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