Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Inhibitors – NC Standard

Restricted Products:

• Praluent® (alirocumab)
• Repatha® (evolocumab)

FDA Approved Use:

Praluent is a PCSK9 inhibitor antibody 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 lipid-lowering therapies (e.g., statins, ezetimibe), for the treatment of adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) to reduce low-density lipoprotein cholesterol (LDL-C).
• As an adjunct to diet and other LDL-C lowering therapies in pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia to reduce LDL-C
• As an adjunct to other low-density lipoprotein cholesterol (LDL-C) lowering therapies in adult patients with homozygous familial hypercholesterolemia to reduce LDL-C.

Repatha is a PCSK9 inhibitor antibody indicated:

• To reduce the risk of myocardial infarction, stroke, and coronary revascularization in adults with established cardiovascular disease.
• As an adjunct to diet, alone or in combination with other lipid-lowering therapies, for treatment of adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia HeFH) to reduce low-density lipoprotein cholesterol (LDL-C).
• As an adjunct to diet and other LDL-C-lowering therapies in pediatric patients aged 10 years and older with HeFH, to reduce LDL-C.
• As an adjunct to other LDL-C-lowering therapies in adults and pediatric patients aged 10 years and older with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C.

Criteria for Approval of Restricted Product(s):

1. The patient has ONE of the following:
   1. 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 low-density lipoprotein hypercholesterolemia (LDL-C) level >190 mg/dL (>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 LDL-C ≥ 100 mg/dL after treatment with antihyperlipidemic agents but prior to PCSK9 inhibitor therapy; OR
   2. 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 >500 mg/dL (>13 mmol/L) or treated LDL-C ≥300 mg/dL (≥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. A diagnosis of clinical atherosclerotic cardiovascular disease (ASCVD) AND BOTH of the following:
      1. The patient is 18 years of age or greater; AND
      2. The patient 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. Stroke
         6. Transient ischemic attack
         7. Peripheral arterial disease, including aortic aneurysm, presumed to be of atherosclerotic origin; OR
   4. The patient has primary hyperlipidemia AND BOTH of the following:
      1. The patient is 18 years of age or greater; AND
      2. ONE of the following:
         1. The patient has a coronary artery calcium or calcification (CAC) score ≥300 Agatston units; OR
         2. The patient has an LDL-C level ≥ 220 mg/dL (≥5.7 mmol/L) while receiving maximally tolerated statin and ezetimibe therapy; OR
   5. The patient has ≥20% 10-year ASCVD risk AND ONE of the following:
      1. The patient has ≥40% 10-year ASCVD risk AND BOTH of the following:
         1. LDL-C ≥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 ≥40% stenosis in ≥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 ≥100 mg/dL, less than high–intensity statin therapy, chronic kidney disease, poorly controlled hypertension, high-sensitivity C-reactive protein >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 ≥220 mg/dL with ≥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 ≥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 ≥2 years prior, and no coronary artery bypass grafting); AND
         3. Adverse or poorly controlled cardiometabolic risk factor(s) including age ≥65 years, current smoking, chronic kidney disease, lipoprotein(a) ≥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 ≥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 <100 mg/dL, blood pressure <140/90 mm Hg, and C-reactive protein <1 mg/dL); OR
            2. The use is for primary prevention with LDL-C ≥220 mg/dL AND BOTH of the following:
               1. No clinical ASCVD or CAC <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 ≥20 mg daily, atorvastatin ≥40 mg daily) for ≥8 continuous weeks AND ONE of the following:
      1. The patient’s LDL-C level after this treatment regimen remains ≥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:
         1. The patient’s non-HDL-C level after this treatment remains ≥100 mg/dL; OR
         2. The patient is at very high risk and the patient’s LDL-C level after this treatment regimen remains ≥55mg/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; AND
3. The patient will NOT be using the requested agent in combination with another PCSK9 agent; AND
4. The patient does not have any FDA labeled contraindications to the requested agent; AND
5. If requesting Praluent:
   1. The patient has tried and failed or has a clinical contraindication to Repatha; OR
   2. The patient is at least 8 years of age and less than 10 years of age, with heterozygous familial hypercholesterolemia; AND
6. For formularies that exclude (non-formulary) the requested medication, Non-formulary Exception Criteria applies.

Duration of Approval: 365 days (1 year)

Continuation Criteria:

1. The patient has a prior approval for this medication from Blue Cross NC; AND
2. If requesting Praluent:
   1. The patient has tried and failed or has a clinical contraindication to Repatha; OR
   2. The patient is at least 8 years of age and less than 10 years of age, with heterozygous familial hypercholesterolemia; AND
3. The patient has shown clinical benefit with PCSK9; AND
4. The patient is currently adherent to therapy with a PCSK9; AND
5. ONE of the following:
   1. The patient is currently adherent to high-intensity statin therapy (i.e. rosuvastatin ≥20 mg, atorvastatin ≥40 mg); 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 patient will NOT be using the requested agent in combination with another PCSK9 agent; AND
7. The patient does not have any FDA labeled contraindications to the requested agent.

Duration of Approval: 365 days (1 year)

Quantity limitations apply to brand and associated generic products

Quantity Limit Exception Criteria:

1. The quantity (dose) requested is for documented titration purposes at the initiation of therapy (authorization for a 90 day titration period); AND
2. The prescribed dose cannot be achieved using a lesser quantity of a higher strength; AND
3. The quantity (dose) requested does not exceed the maximum FDA labeled dose, when specified, or to the safest studied dose per the manufacturer’s product insert; OR
4. If the quantity (dose) requested exceeds the maximum FDA labeled dose, when specified, or to the safest studied dose per the manufacturer’s product insert, then the prescriber must submit documentation in support of therapy with a higher dose for the intended diagnosis (submitted documentation may include medical records OR fax form which reflects medical record documentation that shows the length of time the requested dose has been used, and what other medications and doses have been tried and failed).

References:

All information referenced is from FDA package insert unless otherwise noted below.

1. Identification and Management of Familial Hypercholesterolemia. Simon Broome Diagnostic criteria for index individuals and relatives.:http://www.ncbi.nlm.nih.gov/books/NBK53810/.
2. 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.
3. 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/
4. World Health Organization. Familial Hypercholesterolaemia (FH): Report of a second WHO consultation. Geneva: World Health Organization; 1999
5. 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.
6. Gidding S, Champagne M, Ferranti S, et al. The Agenda for Familial Hypercholesterolemia. A Scientific Statement From the American Heart Association. Circulation. 2015; 132:00-00doi.10.1093/eurheartj/eht273.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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) 2022, 1366-1418. https://www.sciencedirect.com/science/article/pii/S0735109722055942?ref=pdf_download&fr=RR-2&rr=7edef3f3691926bb

Policy Implementation/Update Information:

Criteria and treatment protocols are reviewed annually by the Blue Cross NC P&T Committee, regardless of change. This policy is reviewed in Q2 annually.

September 2024: Criteria update: Increased Repatha 140 mg/mL QL due to discontinuation of Repatha Pushtronex 420 mg/3.5mL

April 2024: Criteria change: Added expanded indication for Praluent. Updated criteria to allow Praluent for members 8-10 years of age.

April 2024: Criteria change: Created NC Standard policy. Added restriction on Repatha on Net Results.

August 2023: Criteria change: Added criteria for very high risk patients with LDL ≥55mg/dL after high intensity statin therapy

February 2023: Criteria update: Annual review. No changes to criteria.

September 2022: Criteria update: Removed preferred NDCs for Repatha (72511075001, 72511076001, 72511076002, 72511077001) and Praluent (61755002002, 61755002102, 72733590102, 72733590202) from the policy.

October 2021: Criteria update: Updated Repatha expanded age indication under FDA approved use section.

September 2021: Criteria change: Increased Repatha Pushtronex QL to 2 systems per 30 days due to labeling change.

April 2021: Criteria change: Added expanded indication for Praluent for the diagnosis of HoFH. Addition of preferred NDCs (61755002002, 61755002102).

*Additional historical revisions available upon request from BCBSNC Corporate Pharmacy