CurrentCignaPolicy IP0128

Evkeeza (evinacumab-dgnb) for Homozygous Familial Hypercholesterolemia

Defines Cigna's coverage criteria, prior authorization requirements, dosing, and not-covered uses for Evkeeza as adjunct therapy for patients with homozygous familial hypercholesterolemia (HoFH). Applies to plans administered by Cigna Companies.

Policy Summary

PayerCigna

PolicyEvkeeza (evinacumab-dgnb) for Homozygous Familial Hypercholesterolemia

Policy CodePolicy IP0128

Change TypeClarification and threshold updates

Effective DateAug 15, 2025

Next Review DateN/A

Key ActionObtain prior authorization with required documentation (genetic test results or clinical findings and prior lipid-lowering therapy history) to support approval.

SourceLink

POLICY UPDATE CHANGES

Clarified Initial Therapy versus Currently Receiving Evkeeza criteria and added examples of response to therapy; removed adjunctive phrasing about diet and maximally tolerated statin therapy.

Updated statin intolerance criteria to clearly define statin intolerance with notes and examples.

Changed diagnostic confirmation language from requiring two mutant alleles to phenotypic confirmation and then back to genetic testing confirming (policy text changed across revisions).

Lowered the untreated LDL-C threshold in diagnostic criterion from > 500 mg/dL to > 400 mg/dL and clarified parental-family history requirement to at least one parent.

Added 'documentation required' for genetic or physical findings to confirm HoFH in initial therapy criteria.

≥5Minimum patient age

15 mg/kg q4w

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>400 mg/dLUntreated LDL-C threshold

≥300 mg/dLTreated LDL-C threshold

1 yrStandard approval duration

Coverage Criteria for Evkeeza (evinacumab-dgnb)

FDA-Approved Indication

Covered when ONE of the following is met:

Top-level: Initial Therapy (A) OR Currently Receiving Evkeeza (B)

Approvals are for 1 year

Initial Therapy

Covered when ALL of the following are met:

Initial Therapy (A): i. Patient is ≥ 5 years of age; ii. Diagnostic confirmation (meet ONE of the Diagnostic Confirmation Paths) with documentation; iii. Prior lipid-lowering therapy requirements or statin intolerance as defined; iv. PCSK9 inhibitor trial or alternate qualifying conditions

Approve for 1 year if all subcriteria met; documentation required as specified in Diagnostic Confirmation Paths and Prior Therapy requirements.

Diagnostic Confirmation Paths

Diagnostic confirmation — meet ONE of a, b, or c (documentation required):

Diagnostic confirmation: a) Genetic testing confirming homozygous familial hypercholesterolemia (documentation required); OR b) Untreated LDL-C > 400 mg/dL (documentation required) AND either (1) clinical manifestations of HoFH before age 10 years (eg, cutaneous or tendon xanthomas, arcus cornea, tuberous xanthomas, xanthelasma) OR (2) at least one parent with untreated LDL-C or total cholesterol consistent with familial hypercholesterolemia (example untreated LDL-C ≥ 190 mg/dL and/or untreated total cholesterol > 250 mg/dL); OR c) Treated LDL-C ≥ 300 mg/dL (documentation required) AND either (1) clinical manifestations of HoFH before age 10 years OR (2) at least one parent with untreated LDL-C or total cholesterol consistent with familial FH (example untreated LDL-C ≥ 190 mg/dL and/or untreated total cholesterol > 250 mg/dL)

‘Untreated’ refers to level prior to any antihyperlipidemic therapy; ‘Treated’ refers to level after at least one antihyperlipidemic agent.

Prior Therapy / Statin Intolerance / PCSK9

Prior lipid-lowering therapy requirements or statin intolerance:

Prior therapy or statin intolerance: Either: a) Tried one high-intensity statin (eg, atorvastatin ≥ 40 mg daily or rosuvastatin ≥ 20 mg daily) AND tried high-intensity statin plus ezetimibe for ≥ 8 continuous weeks with LDL-C remaining ≥ 70 mg/dL; OR b) Statin intolerance defined as either (1) statin-related rhabdomyolysis OR (2) skeletal muscle symptoms occurring with separate trials of both atorvastatin and rosuvastatin that resolved upon discontinuation of each respective statin (documentation required)≥ 70 mg/dL after statin ± ezetimibe

Rhabdomyolysis defined by markedly elevated CK (≥10× ULN) with evidence of end-organ damage (eg, acute kidney injury).

PCSK9 or alternatives: Either: a) Tried one PCSK9 inhibitor for ≥ 8 continuous weeks with LDL-C remaining ≥ 70 mg/dL; OR b) Patient known to have two LDL-receptor negative alleles; OR c) Patient age 5–9 years (special allowance)≥ 70 mg/dL after PCSK9 inhibitor

Examples of PCSK9 inhibitors include evolocumab (Repatha) and alirocumab (Praluent).

Patients Currently Receiving Evkeeza

Covered when ALL of the following are met:

Currently Receiving Evkeeza: Prescriber attests the patient has experienced a response to Evkeeza (examples: decreased LDL-C, total cholesterol, non-HDL-C, or apolipoprotein B); if the patient has not previously received Cigna approval for this indication, evaluate under Initial Therapy criteria; restarting therapy requires meeting Initial Therapy criteria.

Approve for 1 year when criteria met; documentation of response recommended.

Evkeeza (evinacumab-dgnb) is considered not medically necessary for any use other than treatment of homozygous familial hypercholesterolemia (HoFH). Specific exclusions include use for heterozygous familial hypercholesterolemia (HeFH) and for other forms of hyperlipidemia (e.g., combined hyperlipidemia, primary hypercholesterolemia, dyslipidemia, or isolated elevated LDL-C).

The policy states the safety and effectiveness of Evkeeza have not been established for patients who do not have HoFH; therefore claims and requests for these non-HoFH indications do not meet medical necessity under this policy.

For clarity, treatments for HeFH (heterozygous familial hypercholesterolemia) are explicitly listed among the conditions for which Evkeeza is not covered because its safety and efficacy have not been established in that population.

Similarly, use of Evkeeza for other non-HoFH hypercholesterolemia diagnoses or nonspecific elevated LDL-C is considered not medically necessary, per the prescribing information and the Conditions Not Covered section of this policy.

Coding, Age, and Thresholds

Considered Medically Necessary CodesHCPCSCovered

J1305

Injection, evinacumab-dgnb, 5 mg

inv-09: Age — Minimum patient age for Evkeeza treatment

Minimum agePatient must be ≥ 5 years of age to qualify for Evkeeza

Source contextPolicy overview and Initial Therapy criteria specify age requirement for HoFH indication

Approval duration noteApprovals are typically for 1 year per FDA-Approved Indication section

inv-10: Untreated LDL-C diagnostic threshold — threshold suggestive of HoFH (untreated)

Untreated LDL-C threshold> 400 mg/dL (LDL-C measured prior to any antihyperlipidemic therapy)

Clinical useAn untreated LDL-C > 400 mg/dL is suggestive of HoFH and may satisfy diagnostic path when documented

Provider Actions, Documentation, and Prior Authorization

Prior Authorization

Prior Authorization Required

Prior Authorization is required for Evkeeza (evinacumab-dgnb) for the FDA‑approved indication of Homozygous Familial Hypercholesterolemia (HoFH). Approvals are typically for 1 year. Documentation is required as noted in the clinical criteria and must be submitted with the prior authorization request (e.g., chart notes, laboratory results, genetic testing reports). Claims lacking required documentation or covered diagnosis/procedure codes will be denied.

Approval duration: 1 year
Documentation may include chart notes, lab tests, claims records, genetic testing reports

Step Therapy

Required Prior Lipid‑Lowering Therapy

For initial authorization in HoFH, documentation must demonstrate a trial of high‑intensity statin therapy and a trial of high‑intensity statin plus ezetimibe for at least 8 continuous weeks, or documentation of statin intolerance per the policy-defined pathway. Include medication names, doses, dates of therapy, LDL‑C values before and after these regimens, and duration of each trial.

Background on HoFH and Therapy Context

Homozygous familial hypercholesterolemia (HoFH) is a rare, inherited disorder characterized by markedly elevated low-density lipoprotein cholesterol (LDL-C) levels due to impaired or absent LDL receptor function, which leads to early and accelerated atherosclerotic cardiovascular disease. Management typically requires combination lipid-lowering strategies and may include high-intensity statins, ezetimibe, PCSK9 inhibitors, lomitapide, lipoprotein apheresis, and adjunctive therapies.

Evkeeza (evinacumab) is an angiopoietin-like 3 (ANGPTL3) inhibitor indicated as adjunctive therapy for patients with HoFH aged ≥ 5 years. Because HoFH confers high ASCVD risk and often fails to achieve adequate LDL-C lowering with standard therapy alone, Evkeeza provides an additional mechanism to reduce LDL-C in this specific patient population, although cardiovascular outcome benefits have not been established.

Definitions and Diagnostic Terms

inv-19: Untreated LDL-C — Definition and use in diagnostic thresholds (e.g., > 400 mg/dL)

DefinitionUntreated LDL‑C = LDL‑C level measured prior to any antihyperlipidemic therapy

Diagnostic roleAn untreated LDL‑C > 400 mg/dL is suggestive of HoFH and used in diagnostic confirmation pathways

Supporting clinical findingsPresence of tendon or cutaneous xanthomas (often before age 10) and parental LDL‑C levels consistent with familial FH strengthen diagnosis

inv-20: Statin intolerance — Criteria describing statin-related rhabdomyolysis or muscle symptoms and trial requirements

Statin intolerance definition (rhabdomyolysis)Statin‑related rhabdomyolysis: statin‑induced muscle breakdown with markedly elevated creatine kinase (≥ 10× ULN) and evidence of end‑organ damage (e.g., substantial Scr increase or myoglobinuria)

Statin intolerance definition (muscle symptoms)

Policy Summary

PayerCigna

PolicyEvkeeza (evinacumab-dgnb) for Homozygous Familial Hypercholesterolemia

Policy CodePolicy IP0128

Change TypeClarification and threshold updates

Effective DateAug 15, 2025

Next Review DateN/A

Key ActionObtain prior authorization with required documentation (genetic test results or clinical findings and prior lipid-lowering therapy history) to support approval.

SourceLink

On This Page

Examples of supporting findingsCutaneous or tendon xanthomas before age 10 and/or parental LDL-C consistent with familial hypercholesterolemia

inv-11: Treated LDL-C diagnostic threshold — threshold used on-therapy for diagnostic pathway

Treated LDL-C thresholdTreated LDL‑C ≥ 300 mg/dL (measured after therapy with at least one antihyperlipidemic agent)

Diagnostic contextA treated LDL‑C ≥ 300 mg/dL can satisfy diagnostic confirmation when combined with clinical manifestations before age 10 or parental LDL-C consistent with familial FH

Examples of antihyperlipidemic agentsStatins, ezetimibe, PCSK9 inhibitors, or lomitapide (Juxtapid) — per policy note

inv-12: Post-therapy LDL-C persistence threshold — LDL-C persistence after statin ± ezetimibe or PCSK9 inhibitor

Post-therapy persistence thresholdLDL‑C remains ≥ 70 mg/dL after high‑intensity statin ± ezetimibe or after PCSK9 inhibitor therapy

Therapy duration requirementStatin + ezetimibe and PCSK9 inhibitor trials are specified as ≥ 8 continuous weeks before assessing LDL‑C persistence

PurposeUsed to determine inadequate response to prior lipid-lowering therapy for Initial Therapy eligibility

High‑intensity statin example doses: atorvastatin ≥ 40 mg daily; rosuvastatin ≥ 20 mg daily

Statin + ezetimibe trial duration: ≥ 8 continuous weeks

If statin intolerance claimed, provide documentation per policy (rhabdomyolysis or documented resolution of muscle symptoms on discontinuation with trials of atorvastatin and rosuvastatin)

Documentation Required

Required Documentation for Initial Therapy

For initial therapy requests, submit supporting documentation confirming HoFH by genetic testing or by clinical/phenotypic findings as specified in the policy. Examples of acceptable documentation include genetic test reports showing pathogenic variants (e.g., LDLR, APOB, PCSK9, LDLRAP1) or records documenting untreated LDL‑C > 400 mg/dL with supporting clinical notes. Documentation is required for approval.

Genetic testing report showing pathogenic variants (LDLR, APOB, PCSK9, LDLRAP1)
If using phenotypic criteria: untreated LDL‑C > 400 mg/dL with supporting clinical documentation

Documentation Required

Dosing and Response Documentation

Document dosing and response for patients receiving Evkeeza. Include prescribed dose (typical dose: 15 mg/kg IV every 4 weeks), infusion dates, and laboratory evidence of clinical response (e.g., reductions in LDL‑C, total cholesterol, non‑HDL‑C, or apolipoprotein B). Continuation approvals rely on prescriber attestation of response and supporting lab data.

Dosing: 15 mg/kg IV no more frequently than once every 4 weeks
Provide LDL‑C and other lipid values showing response while on therapy
If patient restarting therapy, Initial Therapy criteria must be met if no prior approval through Cigna

Denial Risk

Documentation and Coding Requirements

Claims submitted without covered diagnosis/procedure codes or without the required supporting documentation (as outlined above) will be denied. When submitting, use the most appropriate and up‑to‑date codes and include all requested documentation with the prior authorization and claims submission.

Failure to include genetic test reports, lipid panels, medication trials, or prescriber documentation may result in denial
Receipt of sample product does not satisfy documentation requirements

Skeletal muscle symptoms (myopathy or myalgia) occurring with separate trials of atorvastatin and rosuvastatin that resolve upon discontinuation of each statin

Trial requirementsStatin intolerance requires documented separate trials of atorvastatin and rosuvastatin (single‑entity or combination products) with symptom resolution after stopping each agent