UnitedHealthcare Evkeeza (HoFH) Coverage Update

Coverage Criteria for Evkeeza (evinacumab-dgnb)

inv-01: Initial Therapy

Covered when ALL of the following are met for initial therapy:

Initial therapy: Diagnosis of homozygous familial hypercholesterolemia (HoFH) by, or in consultation with, a lipid specialist (e.g., cardiologist, endocrinologist, lipid specialist/lipidologist); andN/A

HoFH confirmation (one of the following): Confirmation of HoFH by either: (1) medical records documenting genetic confirmation of biallelic pathogenic/likely pathogenic variants on different chromosomes at LDLR, APOB, PCSK9, or LDLRAP1 genes (or ≥2 such variants at different loci); OR (2) untreated LDL-C > 400 mg/dL plus either xanthoma before age 10 or evidence of familial hypercholesterolemia in at least one parent;> 400 mg/dL

Genetic confirmation preferred; untreated LDL-C threshold >400 mg/dL is suggestive of HoFH

Age or LDL-C goal: Patient is less than 10 years of age OR patient has failed to achieve an LDL-C goal of < 55 mg/dL despite required background therapy/considerations (see below);LDL-C < 55 mg/dL goal

For pediatric patients, FDA indication applies to ages ≥5 years; follow age-specific labeling

Background lipid therapy: Patient is currently treated with maximally tolerated statin therapy and adjunctive ezetimibe when tolerated, or has documented intolerance/contraindication to these agents;N/A

Documentation of medication history or intolerance required

Concomitant therapies and exclusions: Patient will continue other traditional LDL-C lowering therapies in combination with Evkeeza; Evkeeza will not be used in combination with Juxtapid (lomitapide);N/A

Use with lomitapide is explicitly not permitted

Dosing and authorization duration: Evkeeza dosing is in accordance with FDA-approved labeling; initial authorization will be for no more than 12 months;≤ 12 months

Follow FDA labeling for dose and schedule

inv-02: Continuation of Therapy

Covered when ALL of the following are met for continuation of therapy:

Positive clinical response: Documentation of a positive clinical response to Evkeeza therapy (e.g., chart notes, laboratory evidence of LDL-C reduction),N/A

Positive clinical response should be documented in chart notes/labs

Concomitant therapy and exclusions: Evkeeza will not be used in combination with Juxtapid (lomitapide);N/A

Use with lomitapide is explicitly not permitted

Dosing and authorization duration: Evkeeza dosing is in accordance with FDA-approved labeling; reauthorization will be for no more than 12 months;≤ 12 months

inv-03: Prior Therapy Exceptions

Additional qualifying considerations (any one may apply where specified):

Genetic nonresponse or prior treatment exceptions: Patient has been treated with PCSK9 therapy and did not respond; OR physician attests patient has two LDL-receptor negative alleles (little to no residual function) and therefore would not respond to PCSK9 therapy; OR patient has a history of intolerance or contraindication to PCSK9 therapy;N/A

These items can satisfy treatment history requirements where applicable

Intolerance or prior therapies: Patient has a history of intolerance or contraindication to ezetimibe; OR history of intolerance or contraindication to statins; OR patient has previously been treated with Juxtapid (lomitapide) or has previously undergone lipoprotein apheresis;N/A

Prior therapies or intolerances may substitute for step therapy when documented

Use of Evkeeza in combination with lomitapide (Juxtapid) is explicitly prohibited. The policy requires that Evkeeza will not be used in combination with Juxtapid (lomitapide) for both initial authorization and continuation of therapy; failure to adhere to this limitation is a basis for denial. This restriction reflects the policy’s assessment that concurrent use with lomitapide is not permitted due to insufficient evidence of safety and effectiveness when combined.

This policy is intended to assist in interpreting UnitedHealthcare standard benefit plans and is informational in nature. Coverage decisions must reference the member specific benefit plan document, and where a conflict exists, the member specific plan governs. Verify the member’s plan terms and any applicable federal or state mandates before initiating therapy; prior authorization and other requirements may vary by plan.

Evinacumab (Evkeeza) is indicated and its safety and effectiveness have been established for homozygous familial hypercholesterolemia (HoFH). The policy clarifies that the safety and effectiveness have not been established for treatment of hypercholesterolemia due to other causes, including heterozygous familial hypercholesterolemia (HeFH); therefore use in non-HoFH diagnoses is considered outside the evidence base and is not supported by this coverage guidance.

Coding and Diagnostic Thresholds

Applicable HCPCSHCPCSCovered

J1305

Injection, evinacumab-dgnb, 5 mg.

Diagnosis Codes (reference)ICD-10

E78.010	Homozygous familial hypercholesterolemia [HoFH]
E78.011	Heterozygous familial hypercholesterolemia [HeFH]
E78.019	Familial hypercholesterolemia, unspecified
Z83.42	Family history of FH

Applicable ICD-10 Diagnosis Codes (policy revision)ICD-10

E78.010	Added ICD-10 diagnosis code (as listed in policy changes)
E78.011	Added ICD-10 diagnosis code (as listed in policy changes)
E78.019	Added ICD-10 diagnosis code (as listed in policy changes)
E78.01	Removed ICD-10 diagnosis code (as listed in policy changes)

Untreated LDL-C threshold

Untreated LDL-C threshold> 400 mg/dL

ContextLDL-C > 400 mg/dL is cited as suggestive of HoFH and warrants further evaluation (per professional society guidance).

Supporting findingsWhen untreated LDL-C >400 mg/dL, additional evidence such as xanthoma before age 10 or family history is required for diagnosis without genetic confirmation.

Provider Actions, Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required per the member-specific benefit plan before Evkeeza (J1305) is dispensed. Verify member-specific prior authorization requirements, benefit coverage, and any applicable federal or state mandates prior to submission. In the event of a conflict between this policy and the member-specific plan document, the member-specific plan governs.

Prior authorization per member plan — verify benefit coverage and PA requirements before initiating therapy
UnitedHealthcare may apply third-party criteria tools (e.g., InterQual) to assist in benefit administration

Denial Risk

Triggers for Denial

Denial risk exists when required diagnostic confirmation, concomitant therapy documentation, or exclusion criteria are not met. Common triggers for denial include failure to document genetic confirmation of HoFH, absence of required background LDL-C–lowering therapies or documented intolerance/contraindication, prohibited combinations (for example, use with Juxtapid/lomitapide), or dosing inconsistent with FDA labeling.

Background

Homozygous familial hypercholesterolemia (HoFH) is an autosomal hereditary disorder characterized by markedly elevated low-density lipoprotein cholesterol (LDL-C), tendon and cutaneous xanthomas, and premature atherosclerotic cardiovascular disease. HoFH most often results from bi-allelic pathogenic or likely pathogenic variants affecting genes involved in LDL receptor function (for example, LDLR, APOB, PCSK9, or LDLRAP1), leading to severely impaired clearance of LDL particles and very high untreated LDL‑C levels. Patients with HoFH are at high risk for early-onset cardiovascular events and often require specialized lipid-lowering strategies beyond standard therapy.

Evkeeza (evinacumab-dgnb) is an anti-ANGPTL3 monoclonal antibody indicated as an adjunct to other LDL‑C lowering therapies for patients aged 5 years and older with HoFH. Because HoFH reflects genetically driven, bi-allelic dysfunction in LDL clearance pathways, these patients may have inadequate response to certain therapies (for example, PCSK9 inhibitors) and can present with markedly elevated untreated LDL‑C (levels suggestive of HoFH include LDL‑C > 400 mg/dL). Management typically involves care by clinicians experienced in HoFH, continuation of background LDL‑lowering therapies, and specialized agents such as Evkeeza when criteria are met.

Definitions and Diagnostic Criteria

HoFH diagnostic genetic confirmation

Genetic confirmation requiredBi-allelic pathogenic/likely pathogenic variants on different chromosomes at LDLR, APOB, PCSK9, or LDLRAP1; or ≥2 such variants at different loci.

Use in criteriaGenetic confirmation is accepted as one method to confirm HoFH for coverage determination for Evkeeza initial therapy.

DocumentationSubmission of medical records (chart notes, laboratory values) confirming the genetic findings is required for authorization.

LDL-C threshold suggestive of HoFH

LDL-C threshold> 400 mg/dL

Diagnostic implicationAn untreated LDL‑C >400 mg/dL is suggestive of HoFH and should prompt further evaluation (detailed medical/family history and/or genetic testing).

Policy Revision History

2025-10-01ICD-10 code updateLatest

Updated the list of applicable ICD-10 diagnosis codes: added E78.010, E78.011, and E78.019 and removed E78.01; supporting information updated.

2025-10-01Operational/archive

Archived previous policy version 2025D0104H when the ICD-10 code list was updated.

OpenPayer

Evkeeza (evinacumab-dgnb) — Medical Benefit Drug Policy (HoFH)