Inclisiran (Leqvio) subcutaneous injection — Medical necessity and site-of-care criteria
Customize your policy alerts
Sign up for all Blue Cross Blue Shield - North Carolina policy alerts
Know when Blue Cross Blue Shield - North Carolina releases new policies or updates existing guidance.
Monitor payer policy activity
Medical necessity and site-of-care criteria for inclisiran (Leqvio) administration for patients with hypercholesterolemia, HeFH, and HoFH; applicable to providers requesting coverage from Blue Cross NC.
Adjusted ASCVD 10-year risk threshold from 20% to 10% and adjusted CAC score threshold from 300 to 100 to align with updated guideline recommendations.
Reformatted and clarified HeFH and HoFH diagnostic confirmation criteria and adjusted statin trial requirement to allow maximally tolerated dose rather than specific products/dosing.
Added newly approved Lerochol as an option within PCSK9 inhibitor trial requirement and allowed Repatha-only step requirement to be specific to HoFH.
Added indication and corresponding criteria for patients 12 to 17 years of age with HoFH.
Continuation criteria now require medical record documentation demonstrating clinical benefit (e.g., LDL-C reduction from baseline).
Coverage Criteria for Inclisiran (Leqvio)
Initial Therapy
Covered when ALL of the following are met for initial approval:
Initial Approval - top level
Diagnosis
HeFH
- HeFH Age: Patient is 12 years of age or older
- HeFH Confirmation: Diagnosis confirmed by ONE of: genetic confirmation of one mutant allele (LDLR, Apo-B, PCSK9, or LDLRAP1); OR history of pretreatment LDL-C >190 mg/dL; OR clinical manifestations of HeFH (e.g., cutaneous/tendon xanthomas, arcus cornea); OR 'definite' or 'possible' familial hypercholesterolemia by Simon Broome criteria; OR Dutch Lipid Clinic Network score >5
Medical record documentation required
Hypercholesterolemia
- Hypercholesterolemia Risk/Criteria: One of: clinical ASCVD (history of acute coronary syndrome, myocardial infarction, stable or unstable angina, coronary or other arterial revascularization, stroke, TIA, or peripheral arterial disease presumed atherosclerotic); OR 10-year ASCVD risk >=10%; OR severe hypercholesterolemia (history of pretreatment LDL-C >=190 mg/dL); OR subclinical atherosclerosis (CAC score >=100 Agatston units)
HoFH
- HoFH Age: Patient is 12 to 17 years of age
- HoFH Confirmation: Diagnosis confirmed by ONE of: BOTH genetic confirmation of two mutant alleles at LDLR, Apo-B, PCSK9, or LDLRAP1 without two LDLR null (negative) alleles; OR history of untreated LDL-C >400 mg/dL with early clinical manifestations of HoFH or parental LDL-C consistent with HoFH
Medical record documentation required
Therapy background
- Statin trial or intolerance: Either: prior treatment with and adherence to high-intensity or maximally tolerated statin therapy for >=8 continuous weeks; OR statin intolerance defined by statin-related rhabdomyolysis, muscle symptoms resolving on discontinuation after trials of at least two statins, elevations in hepatic transaminases due to statin; OR FDA contraindication/hypersensitivity to all statins
- PCSK9 inhibitor trial or exception: Either: for HoFH patients specifically tried and had inadequate response to or intolerance/contraindication to Repatha (evolocumab); OR tried and had inadequate response to or intolerance/contraindication to a PCSK9 inhibitor (e.g., Lerochol, Praluent, Repatha); OR intolerant/contraindicated to all PCSK9 inhibitors — medical record documentation required
Repatha requirement applies to HoFH in some criteria
- LDL-C after prior therapies: The patient's LDL-C after the prior regimen remains above goal corresponding to diagnosis and age (e.g., HoFH: >=100 mg/dL for 12–17y and >=100 mg/dL for >=18y; HeFH: >=70 mg/dL for adults [and pediatric thresholds where specified]; ASCVD or major risk factors: >=55 mg/dL) — medical record documentation required
- Prescriber/Specialist: Prescriber is a specialist in the area of the diagnosis or has consulted with such a specialist (e.g., cardiologist, endocrinologist, geneticist, lipid specialist)
- No combination with PCSK9: Patient will NOT be using inclisiran in combination with a PCSK9 inhibitor for the requested indication
- Quantity limits: Requested quantity does NOT exceed the maximum units allowed for the duration of approval (see dosing/units table)
- Site of Care: For administration in inpatient or outpatient hospital settings, Site of Care criteria must be met
Continuation Therapy
Covered when ALL of the following are met for continuation approval:
Continuation Approval
- Prior approval: Patient was previously approved through Blue Cross NC initial criteria OR would have met initial criteria at the time therapy was started
- Clinical benefit: Medical record documentation demonstrates clinical benefit with inclisiran (e.g., reduction in LDL-C from baseline prior to starting therapy)
Documentation required
- Specialist prescriber: Prescriber is a specialist or has consulted a specialist (e.g., cardiologist, endocrinologist, geneticist, lipid specialist)
- No combination with PCSK9: Patient is not using inclisiran in combination with a PCSK9 inhibitor for the same indication
- Quantity limits: Requested quantity does NOT exceed maximum units allowed for the duration of approval (see dosing/units table)
- Site of Care: If administration is in a hospital inpatient or outpatient setting, Site of Care criteria must be met
Administration in an inpatient setting solely for the purpose of receiving the injection or infusion is excluded unless the admission is for another reason and the medical necessity criteria are met. Per Site of Care criteria, inpatient administration may be allowed when the admission is NOT for the sole purpose of administering the medication. For outpatient hospital administration, the injection/infusion is permitted only when the medical necessity criteria are met and ONE of the specified site-of-care conditions is present (e.g., prior severe adverse event to the agent, conditions that increase risk for severe adverse events, inability to adhere to the regimen, new to therapy [initial dose or <3 months since initial dose], or re-initiation of therapy).
Use of inclisiran is not medically necessary when the patient does not meet the policy’s diagnostic, age, or confirmation requirements (for example, documented HeFH, HoFH, or hypercholesterolemia with the specified age thresholds and confirmatory genetic or clinical criteria). Medical necessity also requires documentation of prior therapy or intolerance: patients must have trialed and adhered to a high‑intensity or maximally tolerated statin regimen for ≥8 continuous weeks unless statin intolerant, or have an FDA‑labeled contraindication to all statins; statin intolerance must be documented per policy definitions (e.g., statin‑related rhabdomyolysis, muscle symptoms resolving after trials of ≥2 statins, or transaminase elevations). For some indications, a trial and inadequate response to a PCSK9 inhibitor (e.g., Lerochol, Praluent, Repatha) is required and documentation must be provided. Continuation approvals additionally require medical record evidence of clinical benefit (for example, LDL‑C reduction from baseline) and that post‑therapy LDL‑C thresholds remain above policy-specified cutoffs (e.g., HoFH LDL-C ≥100 mg/dL after prior regimen or the applicable HeFH / ASCVD thresholds outlined in the policy) to support ongoing therapy. Requests that fail to meet these diagnostic, prior‑therapy, age, or LDL‑C threshold requirements are considered not medically necessary.
Billing and Clinical Thresholds
| J1306 | inclisiran (Leqvio) subcutaneous injection |
Provider Responsibilities and Prior Authorization
Prior Authorization Required
Prior authorization is required for inclisiran (Leqvio) and requests must include documentation that demonstrates the medical necessity criteria are met.
- Prior authorization required before administration or coverage.
- Include medical records showing diagnosis, prior therapies, and lab values (LDL-C) as applicable.
Required Trials of Statin and PCSK9 Inhibitor Therapies
All requests must document trials of statin therapy and PCSK9 inhibitor therapy unless an allowable intolerance, contraindication, or hypersensitivity is documented.
- Statin requirement: Patient must have been treated with and adherent to a high-intensity or maximally tolerated statin for ≥ 8 continuous weeks, OR documentation of statin intolerance (rhabdomyolysis; muscle symptoms with trial of ≥2 statins that resolved on discontinuation; elevations in hepatic transaminases), OR FDA-labeled contraindication/hypersensitivity to all statins.
- PCSK9 requirement: Patient must have tried and had an inadequate response despite adherence to Repatha (evolocumab) or another PCSK9 inhibitor, OR have intolerance/contraindication/hypersensitivity to Repatha, OR intolerance/contraindication/hypersensitivity to ALL PCSK9 inhibitors (medical record documentation required).
Required Medical Record Documentation
Medical record documentation must support diagnosis, genetic or clinical confirmation, prior treatment trials, adherence, and post-treatment LDL-C levels when applicable.
- Diagnosis documentation: For HeFH — genetic confirmation of one mutant allele (LDLR, Apo-B, PCSK9, or LDLRAP1) OR pretreatment LDL-C >190 mg/dL OR clinical signs (xanthomas, arcus) OR Simon Broome/Dutch Lipid Clinic scores as specified.
- For HoFH — genetic confirmation of two mutant alleles or untreated LDL-C >400 mg/dL with supporting clinical history (medical record documentation required).
- Prior therapy documentation: Records showing statin therapy duration/adherence or evidence of intolerance/contraindication; records showing PCSK9 inhibitor use, response, or intolerance (including agent name, dates, and LDL-C results).
- Laboratory documentation: Baseline and on-treatment LDL-C values to demonstrate inadequate response or clinical benefit for continuation requests.
Billing and Dosing Documentation
Billing must use HCPCS code J1306 for inclisiran; follow the labeled dosing schedule and observe maximum units per approval period.
- HCPCS: J1306 for inclisiran (Leqvio).
- Dosing: 284 mg subcutaneous injection initially, then 284 mg at 3 months, then 284 mg every 6 months thereafter.
- Maximum units: Initial request = 852 units; Continuation request = 568 units (per policy duration of approval).
Failure to Meet Medical Necessity Criteria
Requests that do not meet the medical necessity criteria will be denied; ensure all diagnostic, age, genetic/clinical confirmation, and prior therapy criteria are met and documented.
- Denial risk if diagnosis criteria (HeFH, HoFH, hypercholesterolemia/ASCVD) or age requirements are not met or documented.
- Denial risk if required trials of statin and PCSK9 inhibitor therapies (or allowable documented intolerances/contraindications) are not shown.
- Denial risk if genetic testing or clinical criteria supporting familial hypercholesterolemia are not provided when required.
Site of Care / Inpatient Denial Risk
Inpatient admissions solely for administration of the injection/infusion are subject to denial; site of care criteria must be met for inpatient or outpatient hospital administration.
- Inpatient: May be allowed only if medical necessity criteria are met AND the inpatient admission is NOT for the sole purpose of administering the injection/infusion.
- Outpatient hospital: Administration allowed only if medical necessity criteria are met AND at least one site-of-care condition applies (e.g., severe prior adverse event, conditions increasing risk for severe events, inability to adhere, new to therapy [initial or <3 months], re-initiation of therapy).
Background on Inclisiran (Leqvio)
Inclisiran (Leqvio) is a small interfering RNA (siRNA) agent used as an adjunct to diet and exercise to reduce low‑density lipoprotein cholesterol (LDL‑C) in eligible patients with hypercholesterolemia, including patients 12 years and older with familial forms of hypercholesterolemia where indicated. The agent is administered via subcutaneous injection with a typical dosing schedule of 284 mg initially, at 3 months, then every 6 months. Clinical efficacy and use considerations are informed by the ORION trials and the FDA‑approved labeling for inclisiran.
Definitions and Key Terms
OpenPayer is powered by Trek Health's payer performance platform. Trek continuously ingests, validates, and normalizes Transparency in Coverage data alongside payer policies and other commercial payer data to create a structured payer intelligence foundation. OpenPayer uses this foundation to deliver personalized search results, dynamically generated policy pages, and tailored policy monitoring based on each user's payers, specialties, billing codes, and areas of interest. The same intelligence powers broader payer performance workflows, including reimbursement benchmarking, contract evaluation, payer negotiations, and financial decision-making.