ModifiedCentenePolicy HIMPA.156

Clinical Policy: Evolocumab (Repatha)

Defines medical necessity, prior authorization, and continuation criteria for evolocumab (Repatha) for Centene-affiliated health plans (excludes New York Exchange plans). Applies to prescribers and reviewers assessing coverage for members seeking Repatha.

Policy Summary

PayerCentene

PolicyEvolocumab (Repatha) coverage — clinical/medical policy

Policy CodePolicy HIMPA.156

Change TypeMaterial updates (2023–2025): dosing, LDL thresholds, coadministration restrictions

Effective DateJun 1, 2021

Next Review DateN/A

Key ActionSubmit prior authorization with provider attestations documenting diagnosis, LDL‑C values, statin use or documented statin intolerance, and the intended Repatha dosing regimen.

SourceLink

POLICY UPDATE CHANGES

1Q 2025 annual review: revised FDA approved indication wording to align CV disease wording with PI; for HoFH, lowered untreated LDL requirement to 400 and revised evidence of HeFH in both parents to evidence of familial hypercholesterolemia in at least one parent.

1Q 2024 annual review: added Leqvio to list of drugs where coadministration is not allowed and required continuation criteria to state treatment plan does not include coadministration with Leqvio, Juxtapid or Praluent.

Per 2022 ACC pathway and specialist feedback: added bypass of ezetimibe trial if member requires 25% additional lowering of LDL, and lowered minimum LDL requirement to 55 mg/dL.

3 monthsInitial approval duration

12 monthsContinuation approval duration

140 mg q2w / 420 mg mo

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420 mg q2wHoFH max dose

HypersensitivityContraindication

C9399, J3590Billing codes

Coverage Criteria

inv-01: Initial Therapy

Covered when ALL of the following are met:

Initial Repatha coverage for primary hyperlipidemia/HeFH/ASCVD: 1) Diagnosis of primary hyperlipidemia (including HeFH) OR ASCVD per provider attestation; 2) For HeFH: provider documents diagnostic criteria (e.g., WHO/Dutch or Simon Broome) and baseline LDL-C thresholds (>=160 mg/dL if <20 years; >=190 mg/dL if >=20 years); 3) For non-HeFH primary hyperlipidemia: confirmatory genetic testing showing a genetically mediated form of primary hyperlipidemia and exclusion of secondary causes (e.g., hypothyroidism, liver disease, renal disease, nephrosis, medications contributing to elevated lipids); 4) Age requirements: >10 years for HeFH; >=18 years for primary hyperlipidemia (non-HeFH) or ASCVD; 5) For members >=18 on statins: member is on Repatha in conjunction with a statin at maximally tolerated dose and has been adherent for >=8 weeks OR meets statin intolerance criteria; 6) For statin-intolerant members: trial of >=2 statins (one hydrophilic) with documentation of SAMS and re-challenge data per policy; 7) Recent LDL-C value within last 60 days as specified by indication; 8) Prescribed by or in consultation with a cardiologist, endocrinologist, or lipid specialist when specified; 9) Treatment plan does not include coadministration with Leqvio, Juxtapid, or Praluent; 10) Dose does not exceed 140 mg SC every 2 weeks or 420 mg SC monthly for most indications.see node text

Approval duration 3 months

inv-02: HoFH Initial Therapy

Covered when ALL of the following are met:

HoFH coverage: 1) Diagnosis of homozygous familial hypercholesterolemia (HoFH) as attested by provider and defined by one of: confirmatory genetic mutation (LDLR, PCSK9, APOB, LDLRAP1), untreated LDL-C >=400 mg/dL, or treated LDL-C >=300 mg/dL (or non-HDL-C >=330 mg/dL) or clinical signs (tendinous/cutaneous xanthomas by age 10); 2) Age criteria: >=10 years for pediatric HoFH (per pediatric labeling) and >=18 years for adults as applicable; 3) Prescribed by or in consultation with a cardiologist, endocrinologist, or lipid specialist; 4) Statin therapy requirements or documented statin intolerance consistent with general criteria (trial of statins or documented SAMS and re-challenge); 5) Treatment plan must not include coadministration with Leqvio, Juxtapid, or Praluent; 6) Dosing: up to 420 mg SC once monthly; may increase to 420 mg every 2 weeks for members receiving lipid apheresis or if a clinically meaningful response is not achieved after 12 weeks of 420 mg monthly; 7) Approval duration 3 months.see node text

inv-03: Continuation Therapy

Covered when ALL of the following are met:

Continued therapy requirements: 1) Member is currently receiving evolocumab via the Centene benefit or previously met initial approval criteria; 2) If statin tolerant, provider attests to adherence to a statin at maximally tolerated dose; 3) Provider attestation of positive response evidenced by LDL-C reduction within the last 3 months since initiation of Repatha therapy; 4) Treatment plan must not include coadministration with Leqvio, Juxtapid, or Praluent; 5) If request is for dose increase, new dose does not exceed allowed doses for indication (140 mg Q2 weeks or 420 mg monthly for most indications; HoFH escalation per label); 6) Approval duration 12 months.see node text

inv-04: Initial and HoFH dosing/coverage criteria

Covered when ALL of the following are met

Primary Indication and Dosing: Member has primary hyperlipidemia (including HeFH) or hypercholesterolemia with ASCVD and prescriber requests evolocumab dosing of either 140 mg SC every 2 weeks or 420 mg SC once monthly.

Standard dosing per product labeling; chunk 30

HoFH specific: For homozygous familial hypercholesterolemia (HoFH): dosing 420 mg SC once monthly; may increase to 420 mg every 2 weeks if a clinically meaningful response is not achieved after 12 weeks of 420 mg monthly; patients on lipid apheresis may initiate or maintain 420 mg every 2 weeks to align with apheresis schedule.

HoFH dosing per label; chunks 30 and 37

Concomitant Lipid Therapy: Member remains on maximally tolerated statin therapy if tolerated; policy references statin intensity categories (see Appendix E) and supports continuation of statin therapy when tolerated.

See Appendices on statin intensity and general info; chunks 24 and 28

inv-05: Examples of updated criteria

Policy contains initial and continuation therapy criteria with updates noted (examples below).

coadministration_restriction: Treatment plan does not include coadministration with Leqvio, Juxtapid, or Praluent

Moved from initial to continuation criteria as of 1Q2024

HoFH_label_alignment: HoFH criteria revised to align with FDA label; option for 420 mg every 2 weeks if clinically meaningful response is not achieved after 12 weeks of 420 mg monthly; pediatric HoFH ezetimibe trial criteria adjusted per SDC updates.12 weeks

RT4 and subsequent annual review updates reflected in 07.13.21, 1Q2022, and 1Q2025 reviews

Non-FDA approved indications that are not specifically addressed in this policy are not authorized unless there is sufficient supporting documentation per the applicable off‑label use policy (for example, HIMPA.154) or other evidence of coverage documentation.

Evolocumab is contraindicated in patients with a documented hypersensitivity to evolocumab.

Treatment plans that include coadministration of evolocumab with Leqvio, Juxtapid, or Praluent are not allowed and should not be requested or approved.

Uses and indications not listed under Section III (Diagnoses/Indications for which coverage is NOT authorized) and uses that do not meet other referenced policies (for example, formulary/no‑coverage or off‑label policies) are not authorized unless the request follows the applicable non‑formulary or off‑label use pathways and documentation requirements described in those policies.

Inclusion or exclusion of specific billing or HCPCS codes in this policy does not guarantee coverage. Coverage and reimbursement remain subject to the member’s benefit plan terms and current professional coding guidance; providers should verify coding and plan rules when submitting claims.

Coding

HCPCS Codes referencedHCPCS

C9399	Unclassified or biologicals drugs
J3590	Unclassified biologics

Referenced HCPCS CodesHCPCS

C9399	Unclassified or biologicals drugs
J3590	Unclassified biologics

LDL-C thresholds — baseline and treated examples for HeFH/HoFH

HeFH baseline LDL-C (age <20)>= 160 mg/dL (baseline, prior to lipid-lowering therapy)

HeFH baseline LDL-C (age >=20)>= 190 mg/dL (baseline, prior to lipid-lowering therapy)

HoFH treated LDL-C exampleTreated LDL-C >= 300 mg/dL (or non-HDL-C >= 330 mg/dL) as an example threshold for HoFH

HoFH untreated LDL-C exampleUntreated LDL-C >= 400 mg/dL (HoFH diagnostic threshold)

Very high risk LDL-C threshold

Very high risk LDL-C thresholdPersistently elevated LDL-C >= 100 mg/dL despite maximally tolerated statin and ezetimibe therapy

Provider Actions & Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for Evolocumab (Repatha). Requests must include the clinical indication, prior lipid‑lowering therapies and intolerances, and the intended dosing regimen and product formulation.

Prior authorization (PA) is required prior to initiation.
Prescriber must specify dosing regimen (e.g., 140 mg SC every 2 weeks, 420 mg SC once monthly, or 420 mg every 2 weeks for HoFH when criteria met) and product formulation (prefilled syringe, SureClick autoinjector, Pushtronex cartridge).

Documentation Required

Prior Authorization and Clinical Criteria — Provider Attestations

Provider must attest to meeting the policy’s clinical criteria rather than submit supporting documentation per the March SDC revision. Attestations must address diagnosis confirmation, baseline and recent LDL‑C values as applicable, statin use/intolerance, genetic or diagnostic criteria for familial hypercholesterolemia, and absence of secondary causes when required.

Initial Therapy Criteria

inv-36: Initial therapy requirements — 1 top-level node

Initial therapy requirements (top-level): See 'Initial Therapy' coverage criteria: diagnosis confirmation (HeFH/primary hyperlipidemia/ASCVD), LDL-C baseline thresholds, age limits, statin trial or documented statin intolerance, required provider attestations, recent LDL measurements, specialist involvement when specified, coadministration exclusions, and dose limits (140 mg Q2 weeks or 420 mg monthly).see criteria

Approval duration 3 months

inv-37: Initial therapy — Initial dosing options per FDA label

Initial dosing: Initiate 140 mg SC every 2 weeks OR 420 mg SC once monthly for primary hyperlipidemia/ASCVD-related hypercholesterolemia; for HoFH initiate 420 mg SC once monthly (may escalate per HoFH criteria).

Per product Dosage and Administration; chunk 30

Continuation / Renewal Criteria

inv-39: Renewal criteria — Continuation/renewal requires specified items

Renewal criteria: 1) Member currently receiving medication via Centene benefit or previously met initial approval criteria; 2) Provider attests to adherence to maximally tolerated statin if statin tolerant; 3) Provider attests to positive clinical response with laboratory results within the last 3 months demonstrating LDL-C reduction since initiation of Repatha; 4) Treatment plan must not include coadministration with Leqvio, Juxtapid, or Praluent; 5) Dose limits apply (140 mg Q2 weeks or 420 mg monthly for most indications; HoFH escalation per label); 6) Approval duration 12 months.see node text

Continuation/renewal requirements; chunk 14

inv-40: Continuation / Dose escalation — Continuation and HoFH escalation per label

HoFH continuation escalation: If after 12 weeks of 420 mg monthly dosing a clinically meaningful response (>=30% LDL reduction from baseline) is not achieved in HoFH, dose may be increased to 420 mg every 2 weeks; members receiving lipid apheresis may initiate or maintain 420 mg every 2 weeks to align with apheresis schedule.

Step Therapy

Step	Requirement	Notes
1	Trial of maximally tolerated statin for ≥8 weeks if tolerated	Per policy: member adherent ≥8 weeks to maximally tolerated dose; high‑intensity statin example: atorvastatin ≥40 mg or rosuvastatin ≥20 mg
If statin intolerant	Documented trials of ≥2 statins including a hydrophilic agent (e.g., pravastatin, fluvastatin, or rosuvastatin) with resolution of symptoms on discontinuation and recurrence on rechallenge	Hydrophilic statins listed as alternatives with fewer adverse reactions; SAMS definition and rechallenge guidance in Appendix H

Step	Requirement	Notes
1	Document statin intolerance or use of a maximally tolerated statin	Policy emphasizes continuation of statin therapy if tolerated; statin intensity categories in Appendix E and moderate intensity examples in Appendix
2	Continue statin therapy if tolerated while on evolocumab	Concomitant statin therapy recommended due to cardiovascular benefit (Appendix H)

Step	Requirement	Notes
1	Statin trial simplified for some members: insufficient response to one high‑intensity statin for 8 weeks or reversible muscle‑related symptoms with rosuvastatin and atorvastatin	Per 1Q2023 update: statin adherence and trial criteria simplified; 8‑week duration noted
2	Ezetimibe trial may be bypassed when criteria met	1Q2023 addition: ezetimibe trial can be bypassed if member requires ~25% additional LDL lowering

Quantity Limits

Evolocumab quantity limits

Quantity limit (evolocumab)420 mg per month (maximum monthly quantity for standard indications)

Maximum HoFH dosing option420 mg every 2 weeks permitted for HoFH if clinically meaningful response not achieved after 12 weeks or for patients on lipid apheresis

Standard dosing referenceStandard dosing regimens: 140 mg SC every 2 weeks or 420 mg SC once monthly (max 420 mg/month)

Site of Care / Product Presentations

Note

Document product presentation and home administration option for 420 mg

When appropriate for self‑administration, note product availability: prefilled syringe and autoinjector (140 mg) and an on‑body infusor option for the 420 mg presentation; indicate the intended site‑of‑care in the request.

Indicate if home administration is intended and specify formulation (prefilled syringe, autoinjector, or on‑body infusor for 420 mg).
On‑body infusor corresponds to the 420 mg cartridge presentation.

Background

Evolocumab (Repatha) is a PCSK9 inhibitor indicated as an adjunct to diet and other lipid‑lowering therapies to reduce low‑density lipoprotein cholesterol (LDL‑C) and to reduce the risk of major adverse cardiovascular events in adults with established cardiovascular disease. It is also indicated for treatment of primary hyperlipidemia (including heterozygous familial hypercholesterolemia) and for homozygous familial hypercholesterolemia in appropriately aged patients. The product is available in self‑administered formulations including a prefilled syringe and autoinjector, with an on‑body infusor option for the 420 mg presentation.

Definitions

HeFH — definition

TermHeterozygous familial hypercholesterolemia (HeFH)

Definition (brief)Genetic/inherited disorder causing elevated LDL-C due to a single mutant allele; referenced in Appendices and diagnostic criteria

Diagnostic referencesSee Appendix D for family history, clinical history, physical exam, cholesterol levels, and DNA analysis scoring

HoFH — definition

TermHomozygous familial hypercholesterolemia (HoFH)

Definition (brief)Severe inherited form of familial hypercholesterolemia: genetic mutation consistent with HoFH or markedly elevated LDL-C (untreated >= 400 mg/dL or treated >= 300 mg/dL) or clinical signs (tendinous/cutaneous xanthoma by age 10)

Revision History & Policy Changes

2025-12-03annual_reviewLatest

1Q 2025 annual review: revised FDA indication wording to align cardiovascular disease wording with product information; for HoFH lowered the untreated LDL requirement to 400 mg/dL and revised familial evidence requirement to at least one parent; Appendix B additions (pravastatin, fluvastatin) and clarified formulation (latex/non-latex)

2024-02-24annual_review

1Q 2024 annual review: added Leqvio to the list of drugs where coadministration is not allowed and moved the coadministration restriction (Leqvio, Juxtapid, Praluent) into continuation criteria

2023-11-08

Policy Summary

PayerCentene

PolicyEvolocumab (Repatha) coverage — clinical/medical policy

Policy CodePolicy HIMPA.156

Change TypeMaterial updates (2023–2025): dosing, LDL thresholds, coadministration restrictions

Effective DateJun 1, 2021

Next Review DateN/A

Key ActionSubmit prior authorization with provider attestations documenting diagnosis, LDL‑C values, statin use or documented statin intolerance, and the intended Repatha dosing regimen.

SourceLink

On This Page

Context — ASCVD high‑risk listPersistently elevated LDL-C >= 100 mg/dL is listed among conditions conferring very high risk in Appendix H

Requirement typeApplies when LDL-C remains >= 100 mg/dL despite maximally tolerated statin + ezetimibe

LDL thresholds updated

Lowered minimum LDL requirementMinimum LDL requirement lowered to 55 mg/dL for some members (1Q2023 update)

HoFH untreated LDL loweredUntreated LDL requirement for HoFH lowered to 400 mg/dL (1Q2025 update)

Rationale/SourceChanges implemented per ACC pathway and subsequent annual reviews documented in policy history

Attest to diagnosis (HeFH, HoFH, primary hyperlipidemia, or ASCVD) and the specific diagnostic criteria used (e.g., Dutch Lipid Network score, Simon Broome, genetic testing, or LDL thresholds).
Attest to baseline LDL‑C prior to lipid‑lowering therapy and recent LDL‑C within policy timeframes where required.
Attest to statin adherence at maximally tolerated dose or specify contraindication/intolerance per Appendix F when applicable.
For primary hyperlipidemia (non‑HeFH), attest genetic testing results or exclusion of secondary causes (e.g., hypothyroidism, liver or renal disease, contributory medications).

Denial Risk

Off‑Label Indications

Requests for non‑FDA (off‑label) indications are NOT authorized under this policy unless supported by HIMPA.154 (for Marketplace) or by evidence of coverage (EOC) documentation that demonstrates sufficient evidence of efficacy and safety.

Off‑label use requires review per HIMPA.154 or applicable EOC.
Absence of explicit policy coverage for an indication does not automatically authorize use.

Billing Rule

Coding Inclusion/Exclusion Caveat

Inclusion or exclusion of any codes in this policy is for informational purposes only and does not guarantee coverage or reimbursement. Providers must reference current professional coding guidance when submitting claims.

HCPCS examples referenced: C9399 (unclassified biologics), J3590 (unclassified biologics) — informational only.
Verify coding and billing instructions with up‑to‑date payer guidance prior to claim submission.

Documentation Required

Required Clinical Attestations and Labs

Required clinical attestations and lab data must be provided: attest to diagnosis and confirmatory criteria, baseline LDL‑C (prior to lipid‑lowering therapy) and recent LDL‑C where specified, and documentation of statin therapy adherence or contraindication/intolerance.

Baseline LDL‑C (pre‑therapy) and recent LDL‑C within policy timeframes (e.g., within 60 days for some pediatric HoFH criteria or within 3 months for continuation).
Attestation of adherence to maximally tolerated statin dose for the required duration (typically at least 8 weeks when statin tolerant) or documentation of contraindication/intolerance per Appendix F.
For genetic diagnoses, include attestations of genetic testing results when required.

Documentation Required

Monitoring Documentation for Continuation

For continuation of therapy, the provider must attest that the member is responding positively to therapy with evidence of LDL‑C reduction and provide LDL‑C lab results from within the last 3 months. If request is for dose increase, attest new dose does not exceed policy maximums.

Continuation requests must include provider attestation of LDL‑C reduction since Repatha initiation with a lab within the last 3 months.
Dose increases: do not exceed 140 mg q2w (or 420 mg monthly) for primary hyperlipidemia/ASCVD; HoFH maximums per policy (420 mg monthly, with option for 420 mg q2w if clinically meaningful response not achieved).
Approval duration is 12 months for continuation when criteria met.

Documentation Required

Required Documentation on PA

Prescribers must specify the intended dosing regimen and product formulation on the PA request and provide details of prior therapies, intolerances, and statin regimen tried or contraindications.

Specify regimen: 140 mg SC every 2 weeks or 420 mg SC once monthly for primary hyperlipidemia/ASCVD; 420 mg monthly (or 420 mg q2w if indicated) for HoFH.
Indicate product formulation: prefilled syringe, SureClick autoinjector (latex and non‑latex options), or Pushtronex cartridge.
Document prior therapies and intolerances, including statin trials (agents, doses, durations) and any ezetimibe use or reasons for bypass where applicable.

Step Therapy

Statin Trial Requirement

Statin trial requirement: for members ≥18 years on statin therapy, providers must attest the member has been adherent for at least 8 weeks to a maximally tolerated statin dose (high‑intensity preferred). If statin is contraindicated or member is statin‑intolerant, attest contraindication or intolerance per policy Appendix F.

High‑intensity statin trial example: atorvastatin ≥40 mg daily or rosuvastatin ≥20 mg daily for a minimum of 8 weeks, unless LDL‑C remained ≥70 mg/dL.
If statin intolerance claimed, document prior trials (e.g., both rosuvastatin and atorvastatin) and resolution of symptoms upon discontinuation where applicable.

Prior Authorization

Ezetimibe Trial Bypass Update (1Q2023)

Per the 1Q2023 update, an ezetimibe trial may be bypassed when the member requires an additional ≥25% lowering of LDL‑C to meet clinical goals. Document the rationale and intended LDL‑C target on the PA.

If bypassing ezetimibe, include documentation of the required percentage LDL‑C reduction goal (≥25%) and clinician justification.
For pediatric HoFH, ezetimibe trial requirements were removed per later SDCs; follow age‑specific policy language.

inv-38: Initial therapy requirements (examples) — revisions over time

ezetimibe_bypass: Ezetimibe trial may be bypassed for members who require an additional ~25% lowering of LDL as allowed per 1Q2023 update.

Added per 1Q2023 annual review to align with ACC pathway and specialist feedback

statin_trial_simplified: Statin adherence/trial criteria simplified: prior requirement reduced to a minimum of 8 weeks of high-intensity statin use or documented reversible muscle-related symptoms associated with both rosuvastatin and atorvastatin; statin intolerance pathway requires trials of >=2 statins including a hydrophilic agent.8 weeks

Per November SDC and documented policy updates

inv-41: Continuation therapy requirements (examples) — updated to include coadministration restrictions and FDA alignment

continuation_coadministration: Treatment plan must not include coadministration with Leqvio, Juxtapid, or Praluent (added to continuation criteria in 1Q2024).

Updated to align with coadministration restrictions; chunks 40 and 41

Dosing implicationHoFH dosing per label: initiate 420 mg SC monthly; may increase to 420 mg every 2 weeks if inadequate response after 12 weeks; apheresis patients may start every 2 weeks

ASCVD — definition

TermAtherosclerotic cardiovascular disease (ASCVD)

Definition (examples)History of myocardial infarction, recent acute coronary syndrome, ischemic stroke, symptomatic peripheral artery disease, or other atherosclerotic vascular disease events as listed in Appendix H

Risk contextASCVD status used to determine indication and risk category (including very high risk when combined with persistent LDL-C elevation)

HeFH diagnostic criteria

Diagnostic componentsHeFH diagnosis based on family history, clinical history, physical exam (e.g., tendon xanthomas, arcus cornealis), cholesterol levels, and DNA analysis scoring per Appendix D

ScoringAppendix D uses five categories (family history, clinical history, physical exam, cholesterol levels, DNA analysis) to produce a total score to classify FH

Simon Broome referenceSimon Broome criteria included in Appendix D as a route to definite FH diagnosis (see Appendix D details)

Simon Broome criteria for definite FH

NameSimon Broome criteria for definite familial hypercholesterolemia

Key elementsRequires elevated total cholesterol or LDL thresholds (e.g., adult LDL > 4.9 mmol/L [~190 mg/dL] or total cholesterol > 7.5 mmol/L) plus either tendon xanthomas (in patient or relative) OR DNA-based evidence of an LDL receptor mutation/defective apoB100

Use in policySimon Broome is listed in Appendix D as an accepted method to establish definite FH for coverage decisions

Smoking definition (tobacco)

Smoking definitionSmoking refers specifically to tobacco use as clarified in Appendix I

ContextAppendix I clarification made during policy reorganization for clarity (1Q2024 review)

ImplicationTobacco smoking listed among high‑risk conditions in ASCVD context (Appendix H) and clarified to mean tobacco use

Per November SDC: reduced required statin adherence duration to 8 weeks, simplified statin trial/failure criteria, and removed the ezetimibe trial requirement in some cases