Effective Date

Date of Origin 

7/1/2023

Praluent®   (alirocumab)

Injection

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 low density lipoprotein cholesterol (LDL-C)- lowering therapies, in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (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

1

Repatha® (evolocumab)

Injection

In adults with established cardiovascular disease to reduce the risk of myocardial infarction, stroke, and coronary revascularization

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 pediatric patients aged 10 years and older with HeFH, to reduce LDL-C

As an adjunct to diet and other LDL-C-lowering therapies in adults and pediatric patients aged 10 years and older with HoFH, to reduce LDL-C

2

Heterozygous familial hypercholesterolemia (HeFH)

Criteria have been developed to aid in diagnosing HeFH. These include the Simon Broome Register criteria and Dutch Lipid clinic Network criteria. (5) Definitive diagnosis of HeFH according to Simon Broome diagnostic criteria requires the patient has one of the following:(3,5)

• • Total cholesterol greater than 6.7 mmol/L or low-density lipoprotein cholesterol (LDL-C) greater than 4.0 mmol/L in a child aged younger than 16 years, or greater than 7.5 mmol/L or LDL-C greater than 4.9 mmol/L in an adult (levels either pre-treatment or highest on treatment) plus tendon xanthomas in the patient, or in first-degree relative (parent, sibling or child), or in second-degree relative (e.g., grandparent, uncle or aunt) OR
• • DNA-based evidence of an LDL receptor mutation, familial defective Apo B-100, or a PCSK9 mutation

Possible diagnosis of HeFH according to Simon Broome diagnostic criteria requires the patient has:(3)

• • Total cholesterol greater than 6.7 mmol/L or low-density lipoprotein cholesterol (LDL-C) greater than 4.0 mmol/L in a child aged younger than 16 years, or greater than 7.5 mmol/L or LDL-C greater than 4.9 mmol/L 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: greater than 7.5 mmol/L in adult first- or second-degree relative or greater than 6.7 mmol/L in child, brother or sister aged younger than 16 years

The Dutch Lipid Clinic Network criteria assign points based on cholesterol levels, family history of hyperlipidemia or cardiovascular disease, clinical presentation, and/or presence of identified genetic mutation affecting plasma LDL-C. (5-7) A definitive diagnosis of HeFH can be made in patients with greater than 8 points. A probable diagnosis can be made in patients with 6-8 points.

Dutch Lipid Clinic Network criteria for diagnosis of heterozygous familial hypercholesterolemia(8)

Homozygous familial hypercholesterolemia (HoFH)

Guidelines advise that diagnosis of HoFH can be made based on genetic or clinical criteria. Genetic confirmation of the HoFH includes confirmation of two mutant alleles at the LDL-R, APOB, PCSK9, or LDLRAP1 genes.(4,6) While genetic testing may provide a definitive diagnosis of HoFH, it is recognized that in some patients, genetic confirmation remains elusive, despite exhaustive investigation; indeed, the existence of additional FH genes cannot be excluded. Historically, HoFH has been most commonly diagnosed based on either an untreated LDL-C plasma concentration greater than 13 mmol/L (greater than 500 mg/dL), or a treated LDL-C concentration of greater than or equal to 8 mmol/L (greater than or equal to 300 mg/dL), accompanied by the presence of cutaneous or tendon xanthomas before the age of 10 years, or the presence of untreated elevated LDL-C levels consistent with HeFH in both parents.(4,6)

According the American Heart Association (AHA), initial treatment for FH should include a high intensity statin.(9) If the LDL-C is not at goal after 3 months of therapy with the high intensity statin and the patient has been adherent, AHA recommends the addition of ezetimibe. For patients who do not respond to this two drug regimen within 3 months, AHA recommends addition of a PCKS9, a bile acid sequestrant, or niacin. Patients with HoFH who require additional therapy despite treatment with the three drug regimen, AHA recommends addition of Juxtapid and LDL apheresis.(9)    

Atherosclerotic Cardiovascular Disease (ASCVD) – Secondary Prevention

The AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline lists the following as clinical ASCVD:

• Acute coronary syndrome (ACS)
• Myocardial infarction (MI)
• Stable or unstable angina or coronary or other arterial revascularization
• Stroke
• Transient ischemic attack (TIA) or peripheral artery disease (PAD) including aortic aneurysm

Management

The AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol states the following regarding PCSK9 therapy(9)

• Severe hypercholesterolemia (LDL-C greater than or equal to 190 mg/dL [greater than or equal to 4.9 mmol/L])
  • In patients 30-75 years of age with heterozygous FH and with an LDL-C level of 100 mg/dL (greater than or equal to 2.6 mmol/L) or higher while taking maximally tolerated statin and ezetimibe therapy, the addition of a PCSK9 inhibitor may be considered
  • In patients 40-75 years of age with a baseline LDL-C level of 220 mg/dL (greater than or equal to 5.7 mmol/L) or higher while receiving maximally tolerated statin and ezetimibe therapy, the addition of a PCSK9 inhibitor may be considered

The AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol states the following regarding PCSK9 therapy:(9)

• Secondary atherosclerotic cardiovascular disease (ASCVD) prevention
  • In patients with clinical ASCVD who are judged to be very high risk and considered for PCSK9 inhibitor therapy, maximally tolerated LDL-C lowering therapy should include maximally tolerated statin therapy and ezetimibe
  • In patients with clinical ASCVD who are judged to be very high risk and who are on maximally tolerated LDL-C lowering therapy with LDL-C 70 mg/dL (greater than or equal to 1.8 mmol/L) or higher or a non-HDL-C level of 100 mg/dL (greater than or equal to 2.6 mmol/L) or higher, it is reasonable to add PCSK9 inhibitor following a clinical-patient discussion about the net benefit, safety, and cost

The AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline categorizes the following statin intensities:(9)

^{a - Although simvastatin 80 mg was evaluated in RCTs, initiation of simvastatin 80 mg or titration to 80 mg is not recommended by the FDA because of the risk of myopathy, including rhabdomyolysis}

The National Lipid Association (NLA) 2019 consensus statement identifies the following patients, who are already on maximally tolerated statin therapy, as most likely to benefit from PCSK9 therapy.(10)

• Extreme high-risk (greater than or equal to 40% 10-year ASCVD risk on maximally tolerated statin therapy) with LDL-C greater than or equal to 70 mg/dL and either of the following:
  • Extensive or active burden of ASCVD (i.e., polyvascular ASCVD, which affects all 3 vascular beds—coronary, cerebrovascular, and peripheral arterial; clinical peripheral arterial disease in addition to coronary and/or cerebrovascular disease; a clinical ASCVD event with multivessel coronary artery disease defined as greater than or equal to 40% stenosis in greater than or equal to 2 large vessels; or recurrent myocardial infarction within 2 years of the initial event) in the presence of adverse or poorly controlled cardiometabolic risk factors
  • Extremely high-risk elevations in cardiometabolic factors with less-extensive ASCVD (i.e., HeFH, diabetes, LDL-C greater than or equal to 100 mg/dL, less than high–intensity statin therapy, chronic kidney disease, poorly controlled hypertension, high-sensitivity C-reactive protein greater than 3 mg/L, or metabolic syndrome, usually occurring with other extremely high–risk or very-high-risk characteristics), usually with other adverse or poorly controlled cardiometabolic risk factors present. Patients with ASCVD and HeFH or severe hyperlipidemia (SH) LDL-C greater than or equal to 220 mg/dL are an additional group of extremely high–risk patients, with greater than or equal to 45% 10- year ASCVD risk despite statin therapy. Statin-treated HeFH patients with coronary artery calcium (CAC) score greater than 100 Agatston units also have about a 45% 10-year ASCVD risk despite statin therapy
• Very high-risk (30-39% 10-year ASCVD risk on maximally tolerated statin therapy) with LDL-C greater than or equal to 100 mg/dL and the following:
  • Less-extensive clinical ASCVD (i.e., no polyvascular ASCVD, no clinical peripheral arterial disease, a prior ASCVD event greater than or equal to 2 years prior, and no coronary artery bypass grafting)
  • Adverse or poorly controlled cardiometabolic risk factor(s) including age greater than or equal to 65 years, current smoking, chronic kidney disease, lipoprotein(a) greater than or equal to 37 nmol/L, high-sensitivity C-reactive protein 1–3 mg/L, metabolic syndrome with a history of myocardial infarction, ischemic stroke, or symptomatic peripheral arterial disease, usually in the presence of other adverse or poorly controlled cardiometabolic risk factors
• High-risk (20-29% 10-year ASCVD risk on maximally tolerated statin therapy) with LDL-C greater than or equal to 130 mg/dL and either of the following:
  • High-risk patients with ASCVD who have the following:
    • Less-extensive ASCVD
    • Well-controlled cardiometabolic risk factors (i.e., no diabetes, nonsmoker, on high-intensity statin with LDL-C less than 100 mg/dL, blood pressure less than 140/90 mm Hg, and C-reactive protein less than 1 mg/dL)
  • Primary prevention patients with HeFH or SH LDL-C greater than or equal to 220 mg/dL and have the following:
    • No clinical ASCVD or CAC less than 100 Agatston units
    • Poorly controlled cardiometabolic risk factor

CAC Agatston score in non-contrast CT can be used for patient risk classification for coronary heart disease:(11,12)

• 0 CAC = no CAC, very low risk,
• 1-99 CAC = mild CAC, mildly increased risk
• 100 - 299 CAC = moderate CAC, moderately increased risk
• greater than or equal to 300 CAC = moderate to severely increased risk

1

Praluent prescribing information. Regeneron. April 2021.

2

Repatha prescribing information. Amgen. September 2021.

3

Identification and Management of Familial Hypercholesterolemia. Simon Broome Diagnostic criteria for index individuals and relatives.:http://www.ncbi.nlm.nih.gov/books/NBK53810/.

4

Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management.  A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. July 22, 2014. https://academic.oup.com/eurheartj/article/35/32/2146/2481389.

5

National Collaborating Centre for Primary Care (UK). Identification and Management of Familial Hypercholesterolaemia (FH) [Internet]. London: Royal College of General Practitioners (UK); 2008 Aug. (NICE Clinical Guidelines, No. 71.) 3, Diagnosis. http://www.ncbi.nlm.nih.gov/books/NBK53817/

6

World Health Organization. Familial Hypercholesterolaemia (FH): Report of a second WHO consultation. Geneva: World Health Organization; 1999

7

Nordestgaard BG, Chapman MJ, Humphries ST, et al; for the European Atherosclerosis Society Consensus Panel. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease. Eur Heart J. 2013. doi.10.1093/eurheartj/eht273.

8

Gidding S, Champagne M, Ferranti S, et al. The Agenda for Familial Hypercholesterolemia. A Scientific Statement From the American Heart Association. Circulation. 2015; 132:00-00

9

2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol. Journal of the American College of Cardiology. https://doi.org/10.1016/j.acc.2018.11.003.

10

Robinson JG, Jayanna MB, Brown AS, et al. 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. July-August, 2019. 13(4): 525-537.

11

Hect HS, Cronin P, Blaha M, et al.  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.  J Thorac Imaging.  2017;32(5):W54-S66.

12

Blaha MJ, Mortensen MB, Kianoush S, et al.  Coronary artery calcium scoring.  Is it time for a change in methodology.  J Am Coll Cardiol Imag.  2017;10:923-937.

Praluent

Alirocumab Subcutaneous Soln Prefilled Syringe

75

M ; N ; O ; Y

N

Praluent

alirocumab subcutaneous solution auto-injector

150 MG/ML ; 75 MG/ML

M ; N ; O ; Y

N

Repatha sureclick

evolocumab subcutaneous soln auto-injector

140 MG/ML

M ; N ; O ; Y

N

Repatha pushtronex system

evolocumab subcutaneous soln cartridge/infusor

420 MG/3.5ML

M ; N ; O ; Y

N

Repatha

evolocumab subcutaneous soln prefilled syringe

140 MG/ML

M ; N ; O ; Y

N

Repatha

evolocumab subcutaneous soln prefilled syringe

140 MG/ML

2

SYRNGS

28

DAYS

Repatha pushtronex system

evolocumab subcutaneous soln cartridge/infusor

420 MG/3.5ML

2

CARTS

28

DAYS

Repatha sureclick

evolocumab subcutaneous soln auto-injector

140 MG/ML

2

PENS

28

DAYS

Praluent

Alirocumab Subcutaneous Soln Prefilled Syringe  ; alirocumab subcutaneous solution auto-injector

150 MG/ML ; 75  ; 75 MG/ML

2

SYRNGS

28

DAYS

Praluent

Alirocumab Subcutaneous Soln Prefilled Syringe

75

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Praluent

alirocumab subcutaneous solution auto-injector

150 MG/ML ; 75 MG/ML

Blue Partner ; Commercial ; Health Insurance Marketplace ; SourceRx

Repatha

evolocumab subcutaneous soln prefilled syringe

140 MG/ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Repatha pushtronex system

evolocumab subcutaneous soln cartridge/infusor

420 MG/3.5ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Repatha sureclick

evolocumab subcutaneous soln auto-injector

140 MG/ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Repatha

evolocumab subcutaneous soln prefilled syringe

140 MG/ML

Blue Partner ; Commercial ; Health Insurance Marketplace ; SourceRx

Repatha pushtronex system

evolocumab subcutaneous soln cartridge/infusor

420 MG/3.5ML

Blue Partner ; Commercial ; Health Insurance Marketplace ; SourceRx

Repatha sureclick

evolocumab subcutaneous soln auto-injector

140 MG/ML

Blue Partner ; Commercial ; Health Insurance Marketplace ; SourceRx

Praluent

Alirocumab Subcutaneous Soln Prefilled Syringe  ; alirocumab subcutaneous solution auto-injector

150 MG/ML ; 75  ; 75 MG/ML

Blue Partner ; Commercial ; Health Insurance Marketplace ; SourceRx

PA

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. ONE of the following:
   1. BOTH of the following:
      1. ONE of the following:
         1. The patient has a diagnosis of heterozygous familial hypercholesterolemia (HeFH) AND ONE of the following:
            1. Genetic confirmation of one mutant allele at the LDLR, Apo-B, PCSK9, or 1/LDLRAP1 gene OR
            2. History of LDL-C greater than 190 mg/dL (greater than 4.9 mmol/L) (pretreatment) OR
            3. The patient has clinical manifestations of HeFH (e.g., cutaneous xanthomas, tendon xanthomas, arcus cornea, tuberous xanthoma, or xanthelasma) OR
            4. The patient has “definite” or “possible” familial hypercholesterolemia as defined by the Simon Broome criteria OR
            5. The Patient has a Dutch Lipid Clinic Network Criteria score of greater than 5 OR
            6. The patient has a treated low-density lipoprotein cholesterol (LDL-C) level greater than or equal to 100 mg/dL after treatment with antihyperlipidemic agents but prior to PCSK9 inhibitor therapy OR
         2. The patient has a diagnosis of homozygous familial hypercholesterolemia (HoFH) AND ONE of the following:
            1. Genetic confirmation of TWO mutant alleles at the LDLR, Apo-B, PCSK9, or LDLRAP1 gene OR
            2. History of untreated LDL-C greater than 500 mg/dL (greater than 13 mmol/L) or treated LDL-C greater than or equal to 300 mg/dL (greater than or equal to 7.76 mmol/L) OR
            3. The patient has clinical manifestations of HoFH (e.g., cutaneous xanthomas, tendon xanthomas, arcus cornea, tuberous xanthomas, or xanthelasma) OR
         3. The patient has a diagnosis of clinical atherosclerotic cardiovascular disease (ASCVD) AND has ONE of the following:
            1. Acute coronary syndrome
            2. History of myocardial infarction
            3. Stable or unstable angina
            4. Coronary or other arterial revascularization
            5. History of stroke
            6. History of transient ischemic attack
            7. Peripheral arterial disease, including aortic aneurysm, presumed to be of atherosclerotic origin OR
         4. The patient has a diagnosis of primary hyperlipidemia AND ONE of the following:
            1. The patient has a coronary artery calcium or calcification (CAC) score greater than or equal to 300 Agatston units OR
            2. The patient has an LDL-C level greater than or equal to 220 mg/dL (greater than or equal to 5.7 mmol/L) while receiving maximally tolerated statin and ezetimibe therapy OR
         5. The patient has greater than or equal to 20% 10-year ASCVD risk AND ONE of the following:
            1. The patient has greater than or equal to 40% 10-year ASCVD risk AND BOTH of the following:
               1. LDL-C greater than or equal to 70 mg/dL while on maximally tolerated statin therapy AND
               2. ONE of the following:
                  1. The patient has extensive or active burden of ASCVD (i.e., polyvascular ASCVD, which affects all 3 vascular beds—coronary, cerebrovascular, and peripheral arterial; clinical peripheral arterial disease in addition to coronary and/or cerebrovascular disease; a clinical ASCVD event with multivessel coronary artery disease defined as greater than or equal to 40% stenosis in greater than or equal to 2 large vessels; or recurrent myocardial infarction within 2 years of the initial event) in the presence of adverse or poorly controlled cardiometabolic risk factors OR
                  2. Extremely high-risk elevations in cardiometabolic factors with less-extensive ASCVD (i.e., diabetes, LDL-C greater than or equal to 100 mg/dL, less than high–intensity statin therapy, chronic kidney disease, poorly controlled hypertension, high-sensitivity C-reactive protein greater than 3 mg/L, or metabolic syndrome, usually occurring with other extremely high–risk or very-high-risk characteristics), usually with other adverse or poorly controlled cardiometabolic risk factors present. OR
                  3. Patients with ASCVD and LDL-C greater than or equal to 220 mg/dL with greater than or equal to 45% 10- year ASCVD risk despite statin therapy OR
            2. The patient has 30-39% 10-year ASCVD risk AND ALL of the following:
               1. LDL-C greater than or equal to 100 mg/dL while on maximally tolerated statin therapy AND
               2. Less-extensive clinical ASCVD (i.e., no polyvascular ASCVD, no clinical peripheral arterial disease, a prior ASCVD event greater than or equal to 2 years prior, and no coronary artery bypass grafting) AND
               3. Adverse or poorly controlled cardiometabolic risk factor(s) including age 65 years or older, current smoking, chronic kidney disease, lipoprotein(a) greater than or equal to 37 nmol/L, high-sensitivity C-reactive protein 1–3 mg/L, metabolic syndrome with a history of myocardial infarction, ischemic stroke, or symptomatic peripheral arterial disease, usually in the presence of other adverse or poorly controlled cardiometabolic risk factors OR
            3. The patient has 20-29% 10-year ASCVD risk AND BOTH of the following:
               1. LDL-C greater than or equal to 130 mg/dL while on maximally tolerated statins AND
               2. ONE of the following:
                  1. The patient has less extensive ASCVD and well-controlled cardiometabolic risk factors (i.e., no diabetes, nonsmoker, on high-intensity statin with LDL-C less than 100 mg/dL, blood pressure less than 140/90 mm Hg, and C-reactive protein less than 1 mg/dL) OR
                  2. The use is for primary prevention with LDL-C greater than or equal to 220 mg/dL AND BOTH of the following:
                     1. No clinical ASCVD or CAC less than 100 Agatston units AND
                     2. Poorly controlled cardiometabolic risk factor AND
      2. ONE of the following:
         1. The patient has been adherent to high-intensity statin therapy (i.e., rosuvastatin greater than or equal to 20 mg daily, atorvastatin greater than or equal to 40 mg daily) for greater than or equal to 8 continuous weeks AND ONE of the following:
            1. The patient’s LDL-C level after this treatment regimen remains greater than or equal to 70 mg/dL OR
            2. The patient has not achieved a 50% reduction in LDL-C from baseline after this treatment regimen OR
            3. If the patient has ASCVD, the patient’s non HDL-C level after this treatment regimen remains greater than or equal to 100 mg/dL OR
         2. The patient has been determined to be statin intolerant by meeting one of the following criteria:
            1. The patient experienced statin-related rhabdomyolysis OR
            2. The patient experienced skeletal-related muscle symptoms (e.g., myopathy [muscle weakness] or myalgia [muscle aches, soreness, stiffness, or tenderness]) and BOTH of the following:
               1. The skeletal-related muscle symptoms (e.g., myopathy or myalgia) occurred while receiving separate trials of both atorvastatin AND rosuvastatin (as single-entity or as combination products) AND
               2. When receiving separate trials of both atorvastatin and rosuvastatin (as single-entity or as combination products) the skeletal-related muscle symptoms (e.g., myopathy, myalgia) resolved upon discontinuation of each respective statin therapy (atorvastatin AND rosuvastatin) OR
            3. The patient experienced elevations in hepatic transaminase while receiving separate trials of both atorvastatin and rosuvastatin (as single-entity or as combination products) OR
         3. The patient has a hypersensitivity to atorvastatin AND rosuvastatin OR
         4. The patient has an FDA labeled contraindication to atorvastatin AND rosuvastatin OR
   2. The patient has another FDA approved indication for the requested agent and route of administration OR
   3. The patient has another indication that is supported in compendia for the requested agent and route of administration AND
2. If the patient has an FDA labeled indication, ONE of the following:
   1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
   2. The prescriber has provided information in support of using the requested agent for the patient’s age for the requested indication AND
3. The agent 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 AND
4. The patient will NOT be using the requested agent in combination with another PCSK9 agent for the requested indication AND
5. The patient does NOT have any FDA labeled contraindications to the requested agent AND
6. ONE of the following:
   1. The request is for a preferred agent OR
   2. The patient has tried and had an inadequate response to the preferred agent OR
   3. The patient has an intolerance or hypersensitivity to the preferred agent OR
   4. The patient has an FDA labeled contraindication to ALL preferred agents

Compendia Allowed: AHFS, or DrugDex 1 or 2a level of evidence

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has been previously approved for therapy for PCSK9 inhibitors through the plan’s Prior Authorization process AND
2. ONE of the following:
   1. The request is for a preferred agent OR
   2. The patient has tried and had an inadequate response to the preferred agent OR
   3. The patient has an intolerance or hypersensitivity to the preferred agent OR
   4. The patient has an FDA labeled contraindication to ALL preferred agents AND
3. The patient has shown clinical benefit with a PCSK9 inhibitor AND
4. The patient is currently adherent to therapy with a PCSK9 inhibitor AND
5. If the patient has cardiovascular disease OR hyperlipidemia, then ONE of the following:
   1. The patient is currently adherent to high-intensity statin therapy (i.e., rosuvastatin greater than or equal to 20 mg daily, atorvastatin greater than or equal to 40 mg daily) OR
   2. The patient has been determined to be statin intolerant by meeting one of the following criteria:
      1. The patient experienced statin-related rhabdomyolysis OR
      2. The patient experienced skeletal-related muscle symptoms (e.g., myopathy [muscle weakness] or myalgia [muscle aches, soreness, stiffness, or tenderness]) and BOTH of the following:
         1. The skeletal-related muscle symptoms (e.g., myopathy or myalgia) occurred while receiving separate trials of both atorvastatin AND rosuvastatin (as single-entity or as combination products) AND
         2. When receiving separate trials of both atorvastatin and rosuvastatin (as single-entity or as combination products) the skeletal-related muscle symptoms (e.g., myopathy, myalgia) resolved upon discontinuation of each respective statin therapy (atorvastatin AND rosuvastatin) OR
      3. The patient experienced elevations in hepatic transaminase while receiving separate trials of both atorvastatin and rosuvastatin (as single-entity or as combination products) OR
   3. The patient has a hypersensitivity to atorvastatin AND rosuvastatin OR
   4. The patient has an FDA labeled contraindication to atorvastatin AND rosuvastatin AND
6. The agent 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 AND
7. The patient will NOT be using the requested agent in combination with another PCSK9 agent for the requested indication AND
8. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of approval:  12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

QL

Evaluation

Target Agent(s) will be approved when ONE of the following is met:

1. The requested quantity (dose) does NOT exceed the program quantity limit OR
2. ALL of the following:
   1. The requested quantity (dose) is greater than the program quantity limit AND
   2. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
   3. The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit

Length of approval:  12 months