Subject: PCSK9i Supplemental Specialty PA 6431-A P2026b

Drug

Proprotein Convertase Subtilisin/Kexin type 9 Inhibitors (PCSK9i)

LEROCHOL  (lerodalcibep-liga)

LIPFENDRA  (enlicitide)

PRALUENT  (alirocumab)

REPATHA  (evolocumab)

Policy:

Indications

The indications below including FDA-approved indications and compendial uses are considered a covered benefit provided that all the approval criteria are met and the member has no exclusions to the prescribed therapy.

FDA-Approved Indications^1-4

Lerochol

As an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH).

Lipfendra

As an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH).

Praluent

·        To reduce the risk of major adverse cardiovascular (CV) events (coronary heart disease death, myocardial infarction, stroke, or unstable angina requiring hospitalization) in adults at increased risk for these events.

·        As an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in:

§  Adults with hypercholesterolemia.

§  Adults and pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia (HeFH).

§  Adults with homozygous familial hypercholesterolemia (HoFH).  

Repatha

·        To reduce the risk of major adverse cardiovascular (CV) events (CV death, myocardial infarction, stroke, unstable angina requiring hospitalization, or coronary revascularization) in adults at increased risk for these events.

·        As an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in:

§  Adults with hypercholesterolemia.

§  Adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (HeFH).

§  Adults and pediatric patients aged 10 years and older with homozygous familial hypercholesterolemia (HoFH).

Coverage Criteria

Clinical Atherosclerotic Cardiovascular Disease (ASCVD)^1,2,5,6,10

(Praluent and Repatha only)

Authorization of 12 months may be granted for treatment of ASCVD when all of the following criteria are met:

·        Member has a history of ASCVD or has experienced a cardiovascular event.

·        Member meets either of the following criteria:

§  Member has a current LDL-C level greater than or equal to 70 milligrams per deciliter (mg/dL) or a current non-HDL-C greater than or equal to 100 mg/dL.

§  Member has a current LDL-C level greater than or equal to 55 mg/dL or a current non-HDL-C greater than or equal to 85 mg/dL, and has had one of the following:

·        At least two major ASCVD events (e.g., acute coronary syndrome [ACS] within the past 12 months, history of myocardial infarction, history of ischemic stroke, or symptomatic peripheral artery disease).

·        One major ASCVD event and at least two high-risk conditions (e.g., 65 years of age or older, coronary bypass or percutaneous intervention, current smoker, diabetes, history of congestive heart failure, hypertension, or LDL-C of greater than or equal to 100 mg/dL).

·        Chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR) of 20 milliliters per minute per 1.73 square meters (mL/min/1.73 m²) to 59 mL/min/1.73 m²

·        Member is receiving maximally tolerated statin therapy or has a contraindication or intolerance to statin therapy.

Hypercholesterolemia^1-6,8

Authorization of 12 months may be granted for treatment of hypercholesterolemia when all of the following criteria are met:

·        Member had an untreated (before any lipid-lowering therapy) LDL-C level greater than or equal to 190 mg/dL in the absence of a secondary cause.

·        Member meets either of the following criteria:

§  Member does not have a history of ASCVD and either of the following criteria are met:

·        Member has a current LDL-C level greater than or equal to 70 mg/dL or a current non-HDL-C level greater than or equal to 100 mg/dL in the presence of additional ASCVD risk factors ( e.g., 65 years of age or older, coronary bypass or percutaneous intervention, current smoker, diabetes, history of congestive heart failure, hypertension, LDL-C greater than or equal to 100 mg/dL despite maximally tolerated statin and ezetimibe use), heterozygous familial hypercholesterolemia (HeFH), or subclinical atherosclerosis.

·        Member has a current LDL-C level greater than or equal to 100 mg/dL or a current non-HDL-C level greater than or equal to 130 mg/dL in the absence of additional ASCVD risk factors (e.g., 65 years of age or older, coronary bypass or percutaneous intervention, current smoker, diabetes, history of congestive heart failure, hypertension, LDL-C greater than or equal to 100 mg/dL despite maximally tolerated statin and ezetimibe use), HeFH, or subclinical atherosclerosis.

§  Member has a history of clinical ASCVD and a current LDL-C level greater than or equal to 55 mg/dL or a current non-HDL-C level greater than or equal to 85 mg/dL.

·        Member is receiving maximally tolerated statin therapy or has a contraindication or intolerance to statin therapy.

Heterozygous Familial Hypercholesterolemia (HeFH)^1-6,8

Authorization of 12 months may be granted for treatment of heterozygous familial hypercholesterolemia (HeFH) when all of the following criteria are met:

·        Member meets either of the following criteria:

§  Member is 18 years of age or older and had an untreated (before any lipid-lowering therapy) LDL-C level greater than or equal to 190 mg/dL.

§  Member is less than 18 years of age and the request is for Praluent or Repatha, and had an untreated (before any lipid-lowering therapy) LDL-C level greater than or equal to 160 mg/dL.

·        Member has a current LDL-C level greater than or equal to 70 mg/dL or a current non-HDL-C level greater than or equal to 100 mg/dL.

·        Member is receiving maximally tolerated statin therapy or has a contraindication or intolerance to statin therapy.

Homozygous Familial Hypercholesterolemia (HoFH)^1,2,6,9

(Praluent and Repatha only)

Authorization of 12 months may be granted for treatment of homozygous familial hypercholesterolemia (HoFH) when all of the following criteria are met:

·        Member has a diagnosis of HoFH confirmed by any of the following criteria:

§  Variant in two low-density lipoprotein receptor (LDLR) alleles.

§  Presence of homozygous or compound heterozygous variants in apolipoprotein B (APOB) or proprotein convertase subtilisin-kexin type 9 (PCSK9) gene.

§  Member has compound heterozygosity or homozygosity for variants in the gene encoding low-density lipoprotein receptor adaptor protein 1 (LDLRAP1).

§  Member has an untreated LDL-C of greater than 400 mg/dL and has either of the following:

·        Presence of cutaneous or tendinous xanthomas before the age of 10 years.

·        An untreated LDL-C level of greater than or equal to 190 mg/dL in both parents.

·        Member meets either of the following criteria:

§  Member has a current LDL-C level greater than or equal to 100 mg/dL.

§  Member has a current LDL-C level greater than or equal to 55 mg/dL or non-HDL-C level greater than or equal to 85 mg/dL, and meets either of the following criteria:

§  Member has a history of a clinical ASCVD event.

§  Member has major ASCVD risk factors (e.g., 65 years of age or older, diabetes, history of congestive heart failure, coronary bypass or percutaneous intervention, current smoker, hypertension, LDL-C greater than or equal to 100 mg/dL despite maximally tolerated statin and ezetimibe use).

·        Member is receiving maximally tolerated statin therapy or has a contraindication or intolerance to statin therapy.

Primary Prevention of Atherosclerotic Cardiovascular Disease^5,6,10,11

(Praluent and Repatha only)

Authorization of 12 months may be granted for primary prevention of ASCVD when any of the following criteria is met:

·        Member meets all of the following criteria:

§  Member is 40 years of age to 75 years of age.

§  Member has a diagnosis of diabetes mellitus.

§  Member has a current LDL-C level of greater than or equal to 70 mg/dL or a current non-HDL-C level of greater than or equal to 100 mg/dL.

§  Member is receiving maximally tolerated statin therapy or has a contraindication or intolerance to statin therapy.

·        Member meets all of the following criteria:

§  Member is 30 years of age to 79 years of age.

§  Member has a 10-year estimated ASCVD risk of greater than or equal to 10% as calculated by the Predicting Risk of Cardiovascular Disease Events – Atherosclerotic Cardiovascular Disease (PREVENT-ASCVD) calculator (see Appendix).

§  Member has a current LDL-C level of greater than or equal to 70 mg/dL or a current non-HDL-C level of greater than or equal to 100 mg/dL.

§  Member is receiving maximally tolerated statin therapy in combination with ezetimibe or has a contraindication or intolerance to statin therapy.

·        Member meets all of the following criteria:

§  Member has a coronary artery calcium (CAC) score greater than or equal to 300 Agatston units (AU).

§  Member has a current LDL-C level of greater than or equal to 55 mg/dL or a current non-HDL-C level of greater than or equal to 85 mg/dL.

§  Member is receiving maximally tolerated statin therapy or has a contraindication or intolerance to statin therapy.

Continuation of Therapy

Authorization of 12 months may be granted for members who are continuing therapy with a PCSK9i.

Appendix

PREVENT-ASCVD calculator¹¹

Predicting Risk of Cardiovascular Disease Events – Atherosclerotic Cardiovascular Disease (PREVENT-ASCVD) tool available at: https://professional.heart.org/en/guidelines-and-statements/prevent-calculator.

Place of Service:

Outpatient

The above policy is based on the following references:

1.      Repatha [package insert]. Thousand Oaks, CA: Amgen, Inc.; August 2025.

2.     Praluent [package insert]. Tarrytown, NY: Regeneron Pharmaceuticals, Inc.; October 2025.

3.     Lerochol [package insert]. Cincinnati, OH: LIB Therapeutics; December 2025.

4.     Lipfendra [package insert]. Rahway, NJ: Merck Sharp & Dohme LLC; July 2026.

5.     Blumenthal RS, Morris PB, Gaudino M, et al. 2026 ACC/AHA/AACVPR/ABC/ACPM/AGS/APhA/ ASPC/NLA/PCNA guideline on the management of dyslipidemia: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2026;153:e1154– e1276.

6.     Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 2022 ACC Expert consensus decision pathway on the role of nonstatin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: A report of the American college of cardiologic solution set oversight committee. J Am Coll Cardiol. 2022;80(14):1366–1418.

7.     Jacobson TA, Ito MK, Maki KC, et al. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 1 — full report. J Clin Lipidol. 2015;9:(2)129–169.

8.     McGowan MP, Hosseini Dehkordi SH, Moriarty PM, et al. Diagnosis and treatment of heterozygous familial hypercholesterolemia. J Am Heart Assoc. 2019; 8(24):e013225.

9.     Cuchel M, Raal FJ, Hegele RA, et al. Update on European atherosclerosis society consensus statement on homozygous familial hypercholesterolaemia: new treatments and clinical guidance. Eur Heart J. 2023;44(25):2277-2291.

10.  American Diabetes Association Professional Practice Committee. Cardiovascular disease and risk management: standards of care in diabetes – 2024. Diabetes Care. 2024;47(Suppl 1):S179-S218.

11.    Predicting Risk of cardiovascular disease Events – Atherosclerotic Cardiovascular Disease (PREVENT-ASCVD). Available online: https://professional.heart.org/en/guidelines-and-statements/prevent-calculator. Accessed July 29, 2026.

Copyright Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.

October 01, 2026