Inclisiran (Leqvio®)

Restricted Product(s):

• inclisiran (Leqvio®) subcutaneous injection for administration by a healthcare professional

FDA Approved Use:

• 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 statin therapy

Criteria for Medical Necessity:

The restricted product(s) may be considered medically necessary when the following criteria are met:

Initial Criteria for Approval:

1. The patient is 18 years of age or older; AND 
2. 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, or PCSK9 gene; OR 
   2. History of LDL-C greater than 190 mg/dL (greater than 4.9 mmol/L); OR 
   3. The patient has clinical manifestations of HeFH (e.g., cutaneous xanthomas, tendon xanthomas, arcus cornea); 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 treatment with the requested agent; OR 
3. The patient has a diagnosis of clinical atherosclerotic cardiovascular disease (ASCVD) AND ONE of the following: 
   1. Acute coronary syndrome; OR 
   2. History of myocardial infarction; OR 
   3. Stable or unstable angina; OR 
   4. Coronary or other arterial revascularization; OR 
   5. History of stroke; OR 
   6. History of transient ischemic attack; OR 
   7. Peripheral arterial disease, including aortic aneurysm, presumed to be of atherosclerotic origin; OR 
4. The patient has 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 a greater than or equal to 20% 10-year ASCVD risk AND ONE of the following: 
   1. The patient has a 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 2 or more 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 a 30 to 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 to 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 a 20 to 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  
6. ONE of the following: 
   1. The patient has tried and had an inadequate response to a proprotein convertase subtilisin kexin Type 9 (PCSK9) inhibitor [e.g., Praluent (alirocumab), Repatha (evolocumab)] [medical record documentation required]; OR 
   2. The patient has an intolerance, FDA labeled contraindication, or hypersensitivity to ALL proprotein convertase subtilisin kexin Type 9 (PCSK9) inhibitors [i.e., Praluent (alirocumab), Repatha (evolocumab)] [medical record documentation required]; AND 
7. 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 (prior to treatment with high intensity statin therapy) after this treatment regimen; OR 
      3. If the patient has ASCVD, ONE of the following: 
         1. The patient’s non-HDL-C level after this treatment regimen remains greater than or equal to 100 mg/dL; OR 
         2. The patient is at very high risk and the patient’s LDL-C level after this treatment regimen remains greater than or equal to 55 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; AND 
8. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., cardiologist, endocrinologist, lipid specialist) or has consulted with a specialist in the area of the patient’s diagnosis; AND 
9. The patient will NOT be using the requested agent in combination with a PCSK9 inhibitor [e.g., Praluent (alirocumab), Repatha (evolocumab)] for the requested indication; AND 
10. The requested quantity does NOT exceed the maximum units allowed for the duration of approval (see table below); AND 
11. For requests for injection or infusion administration of the requested medication in an inpatient or outpatient hospital setting, Site of Care Criteria applies (outlined below)* 

Duration of Approval: 365 days (1 year) 

Continuation Criteria for Approval:

1. The patient was approved through Blue Cross NC initial criteria for approval; OR 
2. The patient would have met initial criteria for approval at the time they started therapy; AND 
3. The patient has had clinical benefit with the requested agent; AND 
4. ONE of the following: 
   1. The patient is on a maximally tolerated statin containing lipid-lowering regimen (i.e., rosuvastatin OR atorvastatin); OR 
   2. The patient has an intolerance, FDA labeled contraindication, or hypersensitivity to ALL statin containing lipid-lowering regimens (i.e., rosuvastatin AND atorvastatin); AND 
5. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., cardiologist, endocrinologist, lipid specialist) or has consulted with a specialist in the area of the patient’s diagnosis; AND 
6. The patient will NOT be using the requested agent in combination with a PCSK9 inhibitor [e.g., Praluent (alirocumab), Repatha (evolocumab)] for the requested indication; AND 
7. The requested quantity does NOT exceed the maximum units allowed for the duration of approval (see table below); AND 
8. For requests for injection or infusion administration of the requested medication in an inpatient or outpatient hospital setting, Site of Care Criteria applies (outlined below)*

Duration of Approval: 365 days (1 year) 

*Site of Care Medical Necessity Criteria

1. For requests for injection or infusion administration in an inpatient setting, the injection or infusion may be given if the above medical necessity criteria are met AND the inpatient admission is NOT for the sole purpose of administering the injection or infusion; OR 
2. For requests for injection or infusion administration in an outpatient hospital setting, the injection or infusion may be given if the above medical necessity criteria are met AND ONE of the following must be met: 
   1. History of mild adverse events that have not been successfully managed through mild pre-medication (e.g., diphenhydramine, acetaminophen, steroids, fluids, etc.); OR 
   2. Inability to physically and cognitively adhere to the treatment schedule and regimen complexity; OR 
   3. New to therapy, defined as initial injection or infusion OR less than 3 months since initial injection or infusion; OR 
   4. Re-initiation of therapy, defined as ONE of the following: 
      1. First injection or infusion after 6 months of no injections or infusions for drugs with an approved dosing interval less than 6 months duration; OR 
      2. First injection or infusion after at least a 1-month gap in therapy outside of the approved dosing interval for drugs requiring every 6 months dosing duration; OR
   5. Requirement of a change in the requested restricted product formulation; AND 
3. If the Site of Care Medical Necessity Criteria in #1 or #2 above are not met, the injection or infusion will be administered in a home-based infusion or physician office setting with or without supervision by a certified healthcare professional.  

References:

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

1. Raal FJ, Kallend D, Ray KK, et al.; ORION-9 Investigators. Inclisiran for the treatment of heterozygous familial hypercholesterolemia. N Engl J Med. 2020 Apr;382(16):1520-1530. 
2. Ray KK, Wright RS, Kallend D, et al.; ORION-10 and ORION-11 Investigators. Two phase 3 trials of inclisiran in patients with elevated LDL cholesterol. N Engl J Med. 2020 Apr;382(16):1507-1519. 
3. Writing Committee, Lloyd-Jones DM, Morris PB, 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 Cardiology Solution Set Oversight Committee [published correction appears in J Am Coll Cardiol. 2023 Jan;81(1):104]. J Am Coll Cardiol. 2022;80(14):1366-1418.

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 Q1 annually. 

October 2023: Criteria change: Added newly approved updated indication for primary hyperlipidemia, including HeFH, to reduce low-density lipoprotein cholesterol (LDL-C), as an adjunct to diet and statin therapy. Added associated criteria for primary hyperlipidemia and ≥ 20% 10- year ASCVD risk. Added criteria for very high risk patients with LDL ≥ 55 mg/dL after high intensity statin therapy. Minor formatting changes made throughout policy for consistency and clarity.

July 2022: Coding update: Added HCPCS code J1306 to dosing reference table effective 7/1/2022, deleted C9399, J3490, and J3590 termed 6/30/2022.

March 2022: Criteria change: Updated trial and failure PCSK-9 agents to include any PCSK-9 inhibitor.

February 2022: Original medical policy criteria issued.