Is medical necessity met for Leqvio (inclisiran) 284mg subcutaneously (subq) every 6 months for a patient with hyperlipidemia, unspecified (E78.5) and elevated low-density lipoprotein cholesterol (LDL-C) levels?

Medical Necessity Assessment for Inclisiran (Leqvio) J1306 and 96372

Medical necessity is NOT met for this patient based on the Aetna Clinical Policy Bulletin criteria, as there is no documentation of an untreated baseline LDL-C ≥190 mg/dL, which is a mandatory requirement for coverage in this clinical scenario. 1, 2

Critical Coverage Criteria Analysis

Unmet Requirements

The fundamental barrier to approval is the absence of documented untreated (pre-therapy) LDL-C ≥190 mg/dL:

• The policy explicitly requires an untreated baseline LDL-C ≥190 mg/dL in the absence of secondary causes for patients without established ASCVD 1
• This patient's documented LDL-C values (159 mg/dL in 10/2023,145 mg/dL in 03/2024,166 mg/dL in 12/2024) were all obtained while already on lipid-lowering therapy 1
• The diagnosis code E78.5 (hyperlipidemia, unspecified) does not meet the policy's ICD-10 code requirements, as E78.5 is specifically listed as NOT covered 1
• A calcium score of 0 indicates no established coronary atherosclerosis, which eliminates the ASCVD pathway for approval 3

Partially Met Requirements

Statin intolerance documentation is present but incompletely characterized:

• The patient has documented severe myalgias on simvastatin, rosuvastatin (Crestor), atorvastatin (Lipitor), pravastatin, and pitavastatin (Livalo) 1, 4
• However, the records do not clearly specify whether high-intensity statin therapy (atorvastatin 40-80 mg or rosuvastatin 20-40 mg) was attempted for at least 3 months 1, 5
• The American College of Cardiology recognizes statin intolerance as a valid indication for non-statin therapy, but the policy requires explicit documentation of high-intensity statin trials or contraindication 1, 4

Current LDL-C elevation is documented:

• The patient's most recent LDL-C of 166 mg/dL exceeds the policy threshold of ≥100 mg/dL 1
• This criterion alone is insufficient without meeting the untreated baseline LDL-C requirement 1

Clinical Appropriateness Despite Coverage Denial

Evidence Supporting Clinical Benefit

From a purely clinical perspective, this patient would benefit from inclisiran:

• The FDA-approved indication includes primary hyperlipidemia as an adjunct to diet and statin therapy, which applies to this patient 2
• The American College of Cardiology recommends considering non-statin therapies for patients with documented statin intolerance 1, 4
• Inclisiran demonstrates approximately 50% LDL-C reduction, which would bring this patient's LDL-C from 166 mg/dL to approximately 83 mg/dL 6, 5
• The twice-yearly dosing regimen (284 mg subcutaneously initially, at 3 months, then every 6 months) matches the requested treatment plan 2, 6

Safety profile supports use in statin-intolerant patients:

• Inclisiran has a favorable safety profile with injection site reactions (5.0% vs 0.7% placebo) being the most common adverse event 2, 4
• No muscle-related adverse effects have been reported with inclisiran, making it appropriate for patients with statin myopathy 1, 4
• The patient has already tolerated bempedoic acid (Nexletol), suggesting she can tolerate non-statin lipid-lowering agents 1

Specific Documentation Gaps Preventing Approval

To potentially meet coverage criteria, the following documentation would be required:

1. Untreated baseline LDL-C measurement: A documented LDL-C level ≥190 mg/dL obtained before any lipid-lowering therapy was initiated (this may not be obtainable if never measured) 1

2. High-intensity statin trial documentation: Explicit records showing at least 3 months of treatment with atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily, with documented intolerance 1, 5

3. Alternative diagnosis code: If the patient meets criteria for heterozygous familial hypercholesterolemia (HeFH), this diagnosis would align with FDA-approved indications and potentially different coverage pathways 2, 7

Alternative Coverage Strategies

Consider the following approaches:

• Peer-to-peer review: Request a clinical discussion to explain that the patient's current LDL-C of 166 mg/dL likely represents a significantly reduced level from her true untreated baseline, given her documented statin intolerance and family history 1, 8

• PCSK9 monoclonal antibody trial: Evolocumab (Repatha) or alirocumab (Praluent) have cardiovascular outcomes data and may have different coverage criteria, though the case notes indicate prior denial 1, 5

• Bempedoic acid continuation: While the patient reports affordability issues with bempedoic acid, manufacturer assistance programs may provide access at lower cost 9, 1

• Ezetimibe rechallenge: Although documented as not tolerated, the specific adverse effects are not detailed; if gastrointestinal rather than muscular, this may be manageable 1

Common Pitfalls in Inclisiran Prior Authorization

Avoid these documentation errors:

• Submitting only on-treatment LDL-C values without untreated baseline measurements 1
• Using non-specific diagnosis codes (E78.5) instead of more specific codes that align with coverage criteria 1
• Failing to document specific statin doses and durations of therapy 1, 5
• Not clearly documenting the nature and severity of statin-related adverse effects 1, 4

The requested services for J1306 (inclisiran injection) and 96372 (subcutaneous injection administration) from 05/15/2025 through 08/15/2025 do not meet medical necessity criteria per the applicable Clinical Policy Bulletin 1004, primarily due to absence of documented untreated baseline LDL-C ≥190 mg/dL. 1, 2