ModifiedCignaPolicy IP0249

Hyperlipidemia - Nexlizet

This Cigna Coverage Policy governs prior authorization and medical necessity criteria for Nexlizet for adults with primary hyperlipidemia, heterozygous familial hypercholesterolemia (HeFH), or established cardiovascular disease and describes approval durations and continuation criteria.

Policy Summary

PayerCigna

PolicyHyperlipidemia - Nexlizet

Policy CodePolicy IP0249

Change TypeCriteria and threshold revisions

Effective Date

Next Review Date

Key ActionObtain prior authorization and submit documentation including age, diagnosis meeting indication-specific criteria, LDL-C values after high-intensity statin or evidence of statin intolerance, and genetic testing confirmation for HeFH initial therapy.

SourceLink

POLICY UPDATE CHANGES

Updated coverage policy title from Bempedoic Acid and Ezetimibe to Hyperlipidemia - Nexlizet and clarified 'Initial Therapy' versus 'Currently Receiving Nexlizet' criteria, with added examples of response to therapy.

Removed the statement that use is adjunctive to diet and maximally tolerated statin therapy [unless contraindicated or intolerant].

Updated statin intolerance criteria to clearly define what is considered statin intolerant, with notes and examples.

For established cardiovascular disease indication, changed LDL-C threshold after one high-intensity statin from ≥ 70 mg/dL to ≥ 55 mg/dL based on guideline update.

For heterozygous familial hypercholesterolemia (HeFH) initial therapy, replaced phenotypic confirmation language with requirement that diagnosis be confirmed by genetic testing; changed 'apo B' to 'APOB'.

1 yearduration of approval when criteria met

≥18

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age requirement across indications

55,70 mg/dLLDL-C thresholds

PA requiredauthorization requirement

Genetic testHeFH initial therapy diagnostic

Annualrevision frequency

Coverage Criteria for Nexlizet

FDA-Approved Indication: Established Cardiovascular Disease

Approve for 1 year if the patient meets ALL of the following (A or B):

A or B

A) Initial Therapy
- Age: Patient is ≥ 18 years
- CVD diagnoses: One of: a previous myocardial infarction or history of acute coronary syndrome; OR angina (stable or unstable); OR past history of stroke or transient ischemic attack; OR coronary artery disease; OR peripheral arterial disease; OR prior coronary or other arterial revascularization procedure (examples: CABG, PCI, angioplasty, coronary stent)
- LDL or statin intolerance: Either (a) patient has tried one high-intensity statin (atorvastatin ≥ 40 mg daily or rosuvastatin ≥ 20 mg daily) for ≥ 8 continuous weeks AND LDL-C after this therapy remains ≥ 55 mg/dL; OR (b) patient is statin intolerant as defined in policy (e.g., statin-related rhabdomyolysis or skeletal-related muscle symptoms resolving on discontinuation)LDL-C ≥ 55 mg/dL
  Statin intolerance defined in policy; see documentation requirements
- Preferred criteria are met as listed in policy tables
B) Currently Receiving: Prescriber reports patient experienced a response to therapy (examples: decreased LDL-C, total cholesterol, non-HDL-C, or apolipoprotein B)
If patient was not previously approved by Coverage Review Department, initial therapy criteria must be met

FDA-Approved Indication: Heterozygous Familial Hypercholesterolemia (HeFH)

Approve for 1 year if the patient meets ONE of the following (A or B):

A or B

A) Initial Therapy
- Age: Patient is ≥ 18 years
- HeFH diagnosis: One of: untreated LDL-C ≥ 190 mg/dL (prior to antihyperlipidemic treatment); OR diagnosis confirmed by genetic testing (pathogenic variant in LDLR, APOB, PCSK9, or LDLRAP1); OR meets diagnostic criteria thresholds (Dutch Lipid Network score > 5 or Simon Broome 'definite'/'possible')LDL-C ≥ 190 mg/dL or Dutch Lipid Network score > 5
  Policy updated to require genetic confirmation as an option for diagnosis
- LDL/statin trial:

FDA-Approved Indication: Primary Hyperlipidemia

Approve for 1 year if the patient meets ONE of the following (A or B):

A or B

A) Initial Therapy
- Age: Patient is ≥ 18 years
- Risk features: Either (a) coronary artery calcium score ≥ 300 Agatston units; OR (b) diabetesCAC ≥ 300 Agatston units
- LDL/statin trial: Either (a) patient has tried one high-intensity statin (atorvastatin ≥ 40 mg daily or rosuvastatin ≥ 20 mg daily) for ≥ 8 continuous weeks AND LDL-C after this therapy remains ≥ 70 mg/dL; OR (b) patient is statin intolerant as defined in policyLDL-C ≥ 70 mg/dL

FH diagnostic and coverage-related criteria

Document includes diagnostic criteria and policy-level coverage changes; specific coverage decision logic (Initial Therapy vs Currently Receiving Nexlizet) referenced as clarified in revisions.

Familial Hypercholesterolemia - Definite: Definite FH per Dutch Lipid Network: total score >8 (criteria include raised cholesterol thresholds, tendon xanthomas, DNA mutation evidence).score >8

See Dutch Lipid Network criteria in policy; DNA evidence includes LDLR/APOB/PCSK9 mutations

Familial Hypercholesterolemia - Probable: Probable FH: total score 6-8 with family history criteria (premature MI in relatives) and raised cholesterol thresholds.score 6-8

Family history age cutoffs: second-degree relative <50 years or first-degree relative <60 years

Familial Hypercholesterolemia - Possible: Possible FH: total score 3-5 or specified family history/raised cholesterol combinations per Dutch Lipid Network.

Nexlizet for any other use is considered not medically necessary.

Use of Nexlizet for indications other than those specified in this policy is considered not medically necessary.

Use of Nexlizet for indications not specified by this policy is considered not medically necessary.

Clinical Thresholds and Diagnostic Codes

inv-09: Coronary artery calcium score — ≥ 300 Agatston units

ThresholdCoronary artery calcium (CAC) score ≥ 300 Agatston units

ContextUsed as a qualifying risk feature for Primary Hyperlipidemia initial therapy

Approval durationApprove for 1 year when criteria met

inv-10: LDL-C for established CVD after high-intensity statin — ≥ 55 mg/dL

LDL-C threshold≥ 55 mg/dL after ≥ 8 weeks of one high-intensity statin (atorvastatin ≥ 40 mg or rosuvastatin ≥ 20 mg)

IndicationEstablished cardiovascular disease initial therapy qualifying criterion

Documentation

Prior Authorization, Documentation, and Step Therapy

Prior Authorization

Prior Authorization Required

Prior Authorization is required for benefit coverage of Nexlizet. Approvals are provided for one year when the patient meets the clinical criteria for the specific FDA‑approved indication. A patient who previously met Initial Therapy criteria and is currently receiving Nexlizet only needs to meet continuation criteria (i.e., currently receiving therapy). If prior approval was not previously obtained or the patient is restarting Nexlizet, Initial Therapy criteria must be met.

All approvals provided for 1 year when criteria met.
If patient currently receiving Nexlizet but has not previously received approval through the Coverage Review Department, review under Initial Therapy criteria.

Prior Authorization

Employer Plan Additional Prior Therapy Requirement

For certain Employer Plans/Value Advantage/Drug List Plans, approval requires trial of a PCSK9 inhibitor (for example, Praluent or Repatha) prior to approval of Nexlizet when those specific plan criteria apply.

Applies to Value / Advantage / Total Savings Drug List Plans.

Drug Background and Clinical Context

Nexlizet is an oral combination of bempedoic acid and ezetimibe indicated to reduce LDL-C in adults with primary hyperlipidemia, heterozygous familial hypercholesterolemia (HeFH), or established cardiovascular disease. Clinical outcome data support LDL-C lowering and cardiovascular benefit in selected adult patients; refer to the coverage criteria for indication-specific eligibility, required documentation, and duration of approval.

Definitions and Diagnostic Criteria

inv-27: Nexlizet — Combination tablet description and indication summary

Product descriptionNexlizet is an oral combination tablet containing bempedoic acid (an ATP-citrate lyase inhibitor) and ezetimibe (a cholesterol absorption inhibitor)

Indications summaryIndicated to reduce LDL-C in adults with primary hyperlipidemia, including HeFH, and for adults with established cardiovascular disease as described in policy criteria

Approval contextPrior authorization required; approvals provided for 1 year when clinical criteria are met

inv-28: Statin intolerance (per policy) — Definition and examples (rhabdomyolysis, muscle symptoms with atorvastatin/rosuvastatin trials, etc.)

Policy definitionStatin intolerance includes either statin-related rhabdomyolysis or skeletal-related muscle symptoms occurring with separate trials of atorvastatin and rosuvastatin that resolved upon discontinuation

Policy Revision History

2025-07-15revisionLatest

HeFH initial therapy diagnostic requirement changed from phenotypic confirmation to genetic testing; 'apo B' terminology updated to 'APOB'.

2024-08-15revision

Policy title updated to 'Hyperlipidemia - Nexlizet'; clarified 'Initial Therapy' vs 'Currently Receiving Nexlizet' criteria and added examples of response to therapy; removed statement that use is adjunctive to diet and maximally tolerated statin therapy; statin intolerance criteria were updated; LDL-C threshold for established CVD after one high-intensity statin changed from ≥70 mg/dL to ≥55 mg/dL; clinical criteria added for primary hyperlipidemia.

Policy Summary

PayerCigna

PolicyHyperlipidemia - Nexlizet

Policy CodePolicy IP0249

Change TypeCriteria and threshold revisions

Effective Date

Next Review Date

SourceLink

On This Page

Either (a) patient has tried one high-intensity statin (atorvastatin ≥ 40 mg daily or rosuvastatin ≥ 20 mg daily) for ≥ 8 continuous weeks AND LDL-C after this regimen remains ≥ 70 mg/dL; OR (b) patient is statin intolerant as defined

Statin intolerance defined in policy

Preferred criteria are met as listed in policy tables

B) Currently Receiving: Prescriber reports patient experienced a response to therapy

If not previously approved, initial criteria required

Statin intolerance defined in policy

Preferred product criteria are met as listed in policy tables

B) Currently Receiving: Prescriber reports patient experienced a response to therapy

If not previously approved, initial criteria required

Details per Dutch Lipid Network scoring

HeFH Initial Therapy Genetic Confirmation: For initial therapy for heterozygous familial hypercholesterolemia, the diagnosis must be confirmed by genetic testing.genetic testing positive for LDLR/APOB/PCSK9/LDLRAP1 mutation

Policy language updated to require genetic confirmation for HeFH initial therapy; APOB terminology updated to 'APOB'

Prescribers should document LDL-C value after high-intensity statin to demonstrate threshold

inv-11: LDL-C for HeFH after high-intensity statin — ≥ 70 mg/dL

LDL-C threshold≥ 70 mg/dL after ≥ 8 weeks of one high-intensity statin (atorvastatin ≥ 40 mg or rosuvastatin ≥ 20 mg)

IndicationHeterozygous familial hypercholesterolemia (HeFH) initial therapy qualifying criterion

AlternativeOr documented statin intolerance per policy definitions

inv-12: LDL-C for primary hyperlipidemia after high-intensity statin — ≥ 70 mg/dL

LDL-C threshold≥ 70 mg/dL after ≥ 8 weeks of one high-intensity statin (atorvastatin ≥ 40 mg or rosuvastatin ≥ 20 mg)

IndicationPrimary hyperlipidemia initial therapy qualifying LDL-C criterion

AlternativeOr documented statin intolerance per policy definitions

inv-13: LDL-C threshold for established cardiovascular disease after one high-intensity statin — >= 55 mg/dL

Updated threshold>= 55 mg/dL after one high-intensity statin (changed from ≥70 mg/dL based on guideline update)

ScopeApplies to Established Cardiovascular Disease indication initial therapy

Effective notePolicy revision clarifies initial vs currently receiving criteria and documentation expectations

inv-14: Raised cholesterol (adult) — Total cholesterol >7.5 mmol/L (290 mg/dL) or LDL-C >4.9 mmol/L (190 mg/dL)

Adult total cholesterol cutoffTotal cholesterol >7.5 mmol/L (290 mg/dL)

Adult LDL-C cutoffLDL-C >4.9 mmol/L (190 mg/dL)

UseRaised cholesterol thresholds used in FH classification (adult criteria)

inv-15: Raised cholesterol (child <16y) — Total cholesterol >6.7 mmol/L (260 mg/dL) or LDL-C >4.0 mmol/L (155 mg/dL)

Child total cholesterol cutoffTotal cholesterol >6.7 mmol/L (260 mg/dL)

Child LDL-C cutoffLDL-C >4.0 mmol/L (155 mg/dL)

Age rangeApplies to children <16 years for FH classification thresholds

Example PCSK9 inhibitors: Praluent, Repatha.

Documentation Required

Required Clinical Documentation

Prescriber documentation must support the clinical criteria for the requested indication. Required documentation includes patient age, diagnosis meeting the specific indication criteria, laboratory values (LDL‑C and other lipid panel results) demonstrating thresholds after trial of statin therapy when applicable, and documentation of response to therapy or statin intolerance when claimed.

Document patient age and specific diagnosis (e.g., established cardiovascular disease, HeFH, primary hyperlipidemia).
Include LDL‑C values prior to and after statin trial where specified (examples: ≥55 mg/dL for established CVD after high‑intensity statin; ≥70 mg/dL for HeFH; untreated LDL‑C ≥190 mg/dL for HeFH phenotypes).
If claiming statin intolerance, include documentation meeting statin intolerance definition (rhabdomyolysis with CK ≥10× ULN and evidence of end‑organ injury OR skeletal‑related muscle symptoms with resolution upon statin discontinuation after separate trials of atorvastatin and rosuvastatin).
For HeFH initial therapy, include genetic testing confirmation or prescriber confirmation of diagnostic criteria (Dutch Lipid Network score >5 or Simon Broome criteria).
If requesting continuation, note prescriber statement of clinical response (e.g., decreased LDL‑C, total cholesterol, non‑HDL‑C, or APOB).

Step Therapy

Step Therapy / Statin Background

Some plans may require step therapy that includes prior trial of a PCSK9 inhibitor; step therapy and statin background requirements were clarified in the policy. The policy no longer uses blanket language that Nexlizet is adjunctive to diet and maximally tolerated statin; instead, statin trial or statin intolerance criteria are explicitly defined.

Statin trial requirement: one high‑intensity statin (atorvastatin ≥40 mg or rosuvastatin ≥20 mg) for ≥8 continuous weeks, with LDL‑C thresholds specified per indication.
Statin intolerance defined as either (1) statin‑related rhabdomyolysis or (2) skeletal‑related muscle symptoms during separate trials of atorvastatin and rosuvastatin with symptom resolution upon discontinuation.
Some Employer Plans/Value Advantage/Drug List Plans require a PCSK9 inhibitor trial prior to Nexlizet approval.

Denial Risk

Not Medically Necessary / Not Covered Uses

Nexlizet is considered not medically necessary for any uses other than the FDA‑approved indications and will be denied when requested for other indications.

Requests for Nexlizet for indications other than those specified in this policy will be considered not medically necessary and are subject to denial.
Policy criteria will be updated as new published data are available.

Rhabdomyolysis defined as CK ≥ 10× ULN with evidence of end-organ damage (e.g., ≥0.5 mg/dL increase in Scr or doubling of Scr, or myoglobinuria)

Muscle symptom trialsPolicy requires separate trials of atorvastatin and rosuvastatin with symptom resolution upon discontinuation as examples of statin intolerance

inv-29: Dutch Lipid Network Criteria — Reference to Dutch Lipid Network Criteria for FH classification

ReferenceDutch Lipid Network Criteria (DLNC) used for FH classification and scoring

Use in policyPrescriber may confirm DLNC score >5 as diagnostic threshold for HeFH initial therapy

Scoring elementsIncludes family history, clinical history, physical exam (tendon xanthomas, arcus cornealis), LDL-C ranges and DNA analysis

inv-30: Raised cholesterol — Raised cholesterol thresholds and age-specific LDL-C cutoffs used in FH classification

Raised cholesterol adultTotal cholesterol >7.5 mmol/L (290 mg/dL) or LDL-C >4.9 mmol/L (190 mg/dL)

Raised cholesterol childTotal cholesterol >6.7 mmol/L (260 mg/dL) or LDL-C >4.0 mmol/L (155 mg/dL)

RoleThese age-specific LDL-C/total cholesterol cutoffs are used as part of FH diagnostic scoring in the policy