PCSK9 Inhibitors

POLICY NUMBER

L.5.01.527

Praluent (alirocumab)

Repatha (evolocumab)

Please perform a formulary drug search on your patient’s member ID to ensure the prescription drug is covered under their benefit plan. The medication(s) in this medical policy may not be covered under a specific member’s benefit plan.

DESCRIPTION

Proprotein convertase subtilisin kexin type 9 (PCSK9) is a serine protease synthesized primarily by the liver and intestines. PCSK9 promotes the degradation of low density lipoprotein (LDL) receptors (LDL-R), thus preventing them from being recycled back to the plasma membrane where they can bind more LDL. Evolocumab and alirocumab are monoclonal antibodies that bind to free plasma PCSK9, which inhibits the binding of PCKS9 to LDLR and increases the number of LDL-R available. This allows the liver to remove more LCL-cholesterol (LDL-C) from circulation resulting in lower plasma LDL-C level. 

Repatha (evolocumab) is indicated for the following:

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

• As adjunct to diet and exercise to reduce 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).

Praluent (alirocumab) is indicated:

• To reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease;

• As an adjunct to diet, alone or in combination with other LDL-C-lowering therapies, in adults with primary hyperlipidemia (including HeFH), to reduce LDL-C;

• As an adjunct to other LDL-C-lowering therapies in adult patients with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C; and

• As an adjunct to diet and other LDL-C-lowering therapies in pediatric patients aged 8 years and older with HeFH to reduce LDL-C. 

QUANTITY LIMITS

POLICY

Prior authorization is required.

The use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements.

Praluent (alirocumab) is currently non-covered on all BCBSMS formularies.

Initial Criteria

Repatha (evolocumab) may be considered medically necessary when ALL of the following criteria are met:

1. ONE of the following:

   1. The individual is 18 years of age or older and is at high risk for Acute Coronary Syndrome as identified by ONE of the following:

      1. History of clinical atherosclerotic cardiovascular disease (ASCVD), including at least ONE of the following:

         1. Acute coronary syndromes;

         2. Coronary artery disease (CAD);

         3. History of myocardial infarction (MI);

         4. Stable or unstable angina;

         5. Coronary or other arterial revascularization;

         6. Stroke;

         7. Transient Ischemic Attack (TIA); OR

         8. Peripheral Arterial Disease (PAD); OR

      2. Has calculated 10-year risk of cardiovascular disease >20% using the Framingham Coronary Heart Disease Risk Score or the American College of Cardiology ASCVD Risk Estimator;

   2. The individual is 10 years of age or older with a documented diagnosis of Heterozygous Familial Hypercholesterolemia (HeFH) confirmed by ONE of the following:

      1. Genetic confirmation of one mutant allele at the LDLR, Apo-B, PCSK9, or ARH adaptor protein 1/LDLRAP1 gene locus;

      2. The individual has a Dutch Lipid Clinic Network Criteria score of greater than 8 (See Policy Guidelines); OR

      3. ONE of the following:

         1. Total cholesterol greater than 290 mg/dL (>7.5mmol/L) pretreatment or highest level while on treatment; OR

         2. LDL-C greater than 190mg/dL (>4.9 mmol/L) (pretreatment or highest level while on treatment) AND history of tendon xanthomas in ONE of the following:

            1. The individual;

            2. The individual's first degree relative (i.e. parent, sibling, or child); OR

            3. The individual's second degree relative (i.e. grandparent, uncle, or aunt); OR

   3. The individual is 10 years of age or older and has Homozygous Familial Hypercholesterolemia (HoFH) confirmed by ONE of the following:

      1. Genetic confirmation of two mutant alleles at the LDLR, Apo-B, PCSK9, or ARH adaptor protein 1/LDLRAP1 gene locus; OR

      2. Untreated LDL-C >500mg/dL (>13mmol/L) or treated LDL-C ≥300mg/dL (≥7.76 mmol/L) with ONE of the following:

         1. Cutaneous or tendon xanthoma before 10 years of age; OR

         2. Untreated LDL-C levels consistent with heterozygous FH in both parents [untreated [LDL-C >190mg/dL (>4.9mmol/L)];

2. ONE of the following:

   1. Individual has had an inadequate response to high intensity statin therapy defined as ALL of the following:

      1. Individual has received ≥3 consecutive months of therapy with atorvastatin ≥40mg or rosuvastatin ≥20mg;

      2. Individual has received add-on therapy with ezetimibe or bile acid sequestrants to maximum tolerable statin dose; AND

      3. Individual's LDL-C reduction was <50% from pretreatment baseline OR the individual has an LDL-C ≥70mg/dL (≥1.81 mmol/L);

   2. Individual has had an inadequate response to moderate intensity statin therapy defined as ALL of the following:

      1. Individual has intolerance to high-intensity statin therapy;

      2. Individual has received ≥3 consecutive months of therapy with low or moderate intensity statin therapy (e.g., atorvastatin 10-20mg, rosuvastatin 5-10mg, simvastatin ≥20mg, pravastatin ≥40mg, lovastatin ≥40mg, fluvastatin ≥80mg);

      3. Individual has received add-on therapy with ezetimibe or bile acid sequestrants to maximum tolerable dose of statin; AND

      4. Individual's LDL-C reduction was <50% from pretreatment baseline OR the individual has an LDL-C ≥70mg/dL (≥1.81 mmol/L);

   3. Individual has documented intolerance to at least TWO different statins, one of which must be pravastatin or rosuvastatin, as defined by ALL of the following per the National Lipid Association:

      1. One statin trial at any dose and one trial at lowest daily dose;

      2. Individual was unable to tolerate statin due to intolerable skeletal muscle-related symptoms (documented in medical records) or abnormal biomarkers (increased LFTs or CK elevations) temporarily related to statin use, which are reversible upon discontinuation and reproducible by re-challenge while excluding the following known determinants:

         1. Low body mass index (BMI);

         2. Acute infection;

         3. Untreated or undertreated hypothyroidism;

         4. Severe renal or hepatic dysfunction;

         5. Organ transplant;

         6. Recent severe trauma;

         7. HIV infection;

         8. Vitamin D deficiency;

         9. History of creatine kinase elevation; AND

         10. History of preexisting or unexplained muscle or joint pain; AND

      3. Each statin trial, both initial and re-challenge, shall be at least 2 weeks in duration; OR

   4. Individual has an FDA-labeled contraindication to all statins documented in medical records:

      1. Decompensated (see Child-Pugh Classification of Severity of Liver Disease under Policy Guidelines) liver disease (i.e., individuals with symptomatic complications such as jaundice, ascites, variceal hemorrhage, or hepatic encephalopathy). This does NOT include individuals with stable, chronic liver disease (e.g., Hepatitis B and C, non-alcoholic fatty liver disease, etc.);

      2. Immune-mediated hypersensitivity to the HMG-CoA reductase inhibitor drug class as evidenced by an allergic reaction occurring with at least TWO different statins; AND

      3. Pregnancy;

3. The requested agent will not be used concurrently with another PCSK9 inhibitor;

4. The requested agent is prescribed by, or in consultation with, a cardiologist, an endocrinologist, and/or a physician who focuses in the treatment of cardiovascular (CV) risk management and/or lipid disorders;

5. The individual does not have any contraindication(s) to therapy with the requested agent; AND

6. The prescribed dosage is within the program quantity limits based on FDA approved labeled dosage. 

Length of Approval: 6 months

Renewal Criteria

Repatha (evolocumab) may be considered for renewal when ALL of the following criteria are met:

1. The individual has been previously approved for therapy with the requested agent through BCBSMS PA process;

2. The individual has a documented positive clinical response (i.e., LDL-C reduction to goal and/or significant reduction in LDL-C levels from baseline);

3. If the individual has ASCVD, HeFH, or hyperlipidemia, then ONE of the following:

   1. Individual has been adherent to prescribed statin therapy;

   2. Individual is statin intolerant;

   3. Individual has a hypersensitivity or FDA labeled contraindication to statin therapy; OR

   4. Individual does not require additional therapy as they have met their goal of therapy using a single agent PCSK9 inhibitor;

4. The individual does not have any contraindication(s) to therapy with the requested agent; AND

5. The prescribed dosage is within the program quantity limits based on FDA approved labeled dosage. 

Length of Approval: 12 months

POLICY EXCEPTIONS

State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

Structural Steel Self-Insured Group: Effective 06/16/2025, Repatha is covered without Prior Authorization. (FID#: 89805 Formulary Name: BCBSMS COMM-CUSTOM STEEL) 

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

BCBSMS determines patient medication trials and adherence by a review of pharmacy claims data over the preceding twelve months. Additional information may be requested on a case-by-case basis to allow for proper review. If member is new to BCBSMS and pharmacy records are needed to confirm medication trials and adherence, it is the responsibility of the member and/or requesting provider to obtain said records and submit them to BCBSMS upon request. Medical records from the provider that list previously prescribed medications will not be sufficient to show medication trials or adherence.AdherenceAdherence is defined as proportion of days covered [PDC] of ≥80% for the past 90 days as evidenced by prescription drug claims. If pharmacy refill history is unavailable, a recent pharmacy profile will be requested. 

Dutch Lipid Clinic Network Criteria for Diagnosis of HeFH in Adults

Simon Broome Familial Hypercholesterolemia diagnostic criteria

A “definite” diagnosis of HeFH according to Simon Broome diagnostic criteria requires one of the following:

• Total cholesterol >6.7 mmol/L (259 mg/dL) or LDL-C >4.0 mmol/L (155 mg/dL) in a child/young person, or  Total cholesterol >7.5 mmol/L (290 mg/dL) or LDL-C >4.9 mmol/L (189 mg/dL) in an adult (levels either pre-treatment or highest on treatment) AND tendon xanthomas in the patient or a first-degree relative; OR

• DNA-based evidence of mutation in the LDLR, PCSK9, or APOB gene

A “possible” diagnosis of HeFH according to Simon Broome diagnostic criteria requires the following:

• Total cholesterol >6.7 mmol/L (259 mg/dL) or LDL-C >4.0 mmol/L (155 mg/dL) in a child/young person, or >7.5 mmol/L (290 mg/dL) or LDL-C >4.9 mmol/L (189 mg/dL) in an adult (levels either pre-treatment or highest on treatment) AND at least one of the following:

• • Family history of myocardial infarction: aged younger than 50 years in second-degree relative or aged younger than 60 years in first-degree relative; OR

  • Family history of raised total cholesterol above >7.5 mmol/L (290 mg/dL) in adult first- or second-degree relative or >6.7 mmol/L (259 mg/dL)  in child, brother, or sister aged younger than 16 years.

Child-Pugh Classification of Severity of Liver Disease

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D;

A. consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B. appropriate with regard to standards of good medical practice; and

C. not solely for the convenience of the Member, his or her Provider; and

D. the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of Medically Necessary, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.

POLICY HISTORY

06/15/2019: New policy added.

11/01/2020: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Added drug name to the top of the policy. Policy description updated regarding indications for Repatha. Policy section updated to add that the use of samples by a Member will not be considered current or stable therapy for purposes of Medical Policy review. Medically necessary criteria updated regarding statin therapy. Renewal criteria updated. Policy Guidelines updated to remove information regarding statin intolerance. Added information regarding BCBSMS request for additional information. "Nervous/Mental Conditions" changed to "Mental Health Disorders." Sources updated.

02/01/2023: Policy Exceptions updated to add the following: State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

11/18/2024: Policy statement updated to change prescribing requirements to the following: Repatha was prescribed by, or in consultation with, a cardiologist, an endocrinologist, and/or a physician who focuses in the treatment of cardiovascular (CV) risk management and/or lipid disorders. Policy previously required prescribing by or in consultation with, a Board Certified cardiologist, endocrinologist, or lipid specialist.

06/03/2025: Policy reviewed and approved by the Pharmacy & Therapeutics (P&T) Committee. Policy description updated regarding indications for Repatha (evolocumab) and Praluent (alirocumab). Policy statement revised to state that the use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements. Medically necessary criteria updated regarding age requirement for those with a documented diagnosis of Heterozygous Familial Hypercholesterolemia (HeFH). Added statement regarding dose requirement. Renewal criteria updated regarding a documented positive clinical response, contraindications to therapy, and dose requirements. Policy Guidelines updated regarding Simon Broome Familial Hypercholesterolemia diagnostic criteria. Sources updated.

06/16/2025: Added Self-Insured Group exception.

02/01/2026: Policy description updated regarding indications for Repatha (evolocumab). Policy section revised to remove statement that the requested agent will be prescribed in combination with the maximum tolerated dose of a statin. Renewal statement revised to add criteria for individuals with ASCVD, HeFH, or hyperlipidemia. Sources updated.

SOURCE(S)

1. Blaha, MJ, Mortensen MB, Kianoush S, et al. (2017). Coronary Artery Calcium Scoring: Is It Time for a Change in Methodology? JACC: Cardiovascular Imaging, 10(8), 923–937. https://doi.org/10.1016/j.jcmg.2017.05.007

2. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/ APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018; DOI: 10.1161/CIR.0000000000000625.

3. Guyton JR, Bays HE, Grundy SM, Jacobson TA, The National Lipid Association Statin Intolerance Panel. An assessment by the Statin Intolerance Panel: 2014 update. J Clin Lipidol. 2014;8(3 Suppl):S72-S81. doi:10.1016/j.jacl.2014.03.002.

4. Hecht, HS, Cronin P, Blaha MJ, et al. (2017). 2016 SCCT/STR Guidelines for coronary artery calcium scoring of noncontrast noncardiac chest CT scans: A report of the Society of Cardiovascular Computed Tomography and Society of Thoracic Radiology. Journal of Cardiovascular Computed Tomography, 11, 74–84. https://doi.org/10.1016/j.jcct.2016.11.003

5. Lloyd-Jones D, Morris PB, Ballantyne C, 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. Journal of the American College of Cardiology, 80(14), 1366–1418. https://doi.org/10.1016/j.jacc.2022.07.006

6. National Institute for Health and Care Excellence. (2019, October 4). Familial hypercholesterolaemia: identification and management (NICE Guideline No. 71). https://www.nice.org.uk/guidance/cg71

7. National Institute for Health and Care Excellence. Appendix F Simon Broome Diagnostic Criteria for index individuals and relatives. Familial hypercholesterolaemia: identification and management (NICE Guideline No. 71). (2019, October 4). https://www.nice.org.uk/guidance/cg71/evidence/full-guideline-appendix-f-pdf-241917811

8. Praluent prescribing information. Regeneron Pharmaceuticals, Inc. March 2024. Last accessed April 2025.

9. Repatha prescribing information. Amgen USA Inc. December 2025. Last accessed January 2026.

10. Robinson, JG, Jayanna MB, Brown AS, et al. (2019). Enhancing the Value of PCSK9 Monoclonal Antibodies by Identifying Patients Most Likely to Benefit. A Consensus Statement from the National Lipid Association. Journal of Clinical Lipidology, 13(4). https://doi.org/10.1016/j.jacl.2019.05.005

11. Stroes ES, Thompson PD, Corsini A, et al. Statin associated muscle symptoms: impact on statin therapy – European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. European Heart Journal 2015, epub 18 February 2015.

CODE REFERENCE

None