Anthem Blue Cross California Leqvio (inclisiran) Form

Medical Drug Clinical Criteria Subject: Leqvio (inclisiran) Document #: CC-0209 Status: Revised Table of contents Publish Date: 12/18/2023 Last Review Date: 11/17/2023 Overview Document history References Clinical criteria Coding Overview This document addresses the use of Leqvio (inclisiran), a small interfering RNA (siRNA) directed to proprotein convertase subtilisin kexin type 9 (PCSK9) mRNA approved by the Food and Drug Administration as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD) who require additional lowering of low-density lipoprotein cholesterol (LDL-C). Leqvio is administered by a healthcare provider as a subcutaneous injection on day 1, day 90 and every 6 months thereafter. The effect of Leqvio on cardiovascular morbidity and mortality has not been determined. In the clinical setting, statins are considered first-line drug therapy, in addition to healthy lifestyle interventions, in individuals requiring treatment for abnormal cholesterol. Other lipid lowering therapies should be considered second- line options for individuals needing additional cholesterol lowering or who cannot tolerate moderate to high doses of statins. In 2018, the American Heart Association (AHA)/American College of Cardiology (ACC) released guidelines on the management of blood cholesterol. In very high-risk ASCVD, the guidance recommends considering adding non- statins to statin therapy when LDL-C remains greater than or equal to 70 mg/dL. Ezetimibe is the first agent to consider adding on to maximally tolerated statin therapy. PCSK9 inhibitors can be considered for addition if LDL-C remains greater than or equal to 70 mg/dL on statin therapy combined with ezetimibe. The 2018 AHA/ACC guidelines recommend using an LDL-C threshold of greater than or equal to 100 mg/dL to consider adding non-statins to statin therapy in individuals with severe primary hypercholesterolemia. Ezetimibe is the first non-statin to consider adding to therapy. PCSK9 inhibitors can be considered for addition if LDL-C remains greater than or equal to 100 mg/dL on statin therapy combined with ezetimibe. Statins have labeled warnings for liver enzyme abnormalities and skeletal muscle effects including myopathy and rhabdomyolysis. Statin-induced adverse events leading to some degree of intolerance is reported in as many as 5% to 30% of individuals although incidence and prevalence vary. The National Lipid Association (NLA) has provided guidance defining statin intolerance as one or more adverse effects associated with statin therapy, which resolves or improves with dose reduction or discontinuation, and can be classified as complete inability to tolerate any dose of a statin or partial intolerance, with inability to tolerate the dose necessary to achieve the individual-specific therapeutic objective. To classify an individual as having statin intolerance, a minimum of two statins should have been attempted, including at least one at the lowest approved daily dosage. World Health Organization (WHO)/Dutch Lipid Clinic Network Criteria for Familial Hypercholesterolemia (FH) Diagnosis Criteria Family History Known premature coronary and vascular disease (men <55 years, women <60 years) in first degree relative Known LDL-C >95th percentile in first degree relative Tendon xanthoma and/or corneal arcus in first degree relative Points 1 1 2 1 Children aged <18 years with LDL-C >95th percentile Personal Clinical History Premature coronary artery disease (men <55 years, women <60 years) Premature cerebral or peripheral vascular disease (men <55 years, women <60 years) Clinical Exam Tendon xanthoma Corneal arcus in individual aged <45 years LDL-C Level > 329 mg/dL (>8.5 mmol/L) 250-329 mg/dL (6.5-8.4 mmol/L) 190-249 mg/dL (5.0-6.4 mmol/L) 155-189 mg/dL (4.0-4.9 mmol/L) Genetic Testing Functional mutation in LDLR, ApoB or PCSK9 gene 2 2 1 6 4 8 5 3 1 8 Scoring: Definite FH:> 8 points; Probable FH: 6-8 points; Possible FH: 3-5 points; Unlikely FH: 0-2 points. Clinical criteria When a drug is being reviewed for coverage under a member’s medical benefit plan or is otherwise subject to clinical review (including prior authorization), the following criteria will be used to determine whether the drug meets any applicable medical necessity requirements for the intended/prescribed purpose. Leqvio (inclisiran) Initial requests for Leqvio (inclisiran) may be approved when the following criteria are met: I. Individual is at high risk for atherosclerotic cardiovascular disease (ASCVD) events as identified by one of the following: A. Individual has Heterozygous Familial Hypercholesterolemia (HeFH) verified by (Singh 2015; WHO 1999): 1. Presence of a mutation in LDLR, ApoB, PCSK9 or ARH adaptor protein (LDLRAP1) gene; OR 2. WHO/Dutch Lipid Clinic Network criteria with score of greater than eight points; OR B. Individual has a history of clinical atherosclerotic cardiovascular disease (ASCVD) including one or more of the following (AHA/ACC 2018): 1. 2. 3. 4. 5. 6. 7. 8. Acute coronary syndrome; Coronary artery disease (CAD); History of myocardial infarction (MI); Stable or unstable angina; Coronary or other arterial revascularization; Stroke; Transient ischemic attack (TIA); Peripheral arterial disease (PAD); AND II. Individual meets one of the following: A. B. Individual is on high intensity statin therapy or statin therapy at the maximum tolerated dose (high intensity statin is defined as atorvastatin 40 mg or higher or rosuvastatin 20 mg or higher) (AHA/ACC 2018); OR Individual is statin intolerant based on one of the following: 1. 2. Inability to tolerate at least two statins, with at least one started at the lowest starting daily dose, demonstrated by adverse effects associated with statin therapy that resolve or improve with dose reduction or discontinuation (NLA 2022); OR Statin associated rhabdomyolysis or immune-mediated necrotizing myopathy (IMNM) after a trial of one statin; OR C. Individual has a contraindication for statin therapy including but not limited to active liver disease, unexplained persistent elevation of hepatic transaminases or pregnancy; AND III. Individual has achieved suboptimal lipid lowering response despite at least 90 days of compliant lipid lowering therapy and lifestyle modifications as defined (AHA/ACC 2018, ACC 2022): 2 A. B. For individuals where initial LDL-C is known: 1. Less than 50% reduction in LDL-C; OR For individuals where initial LDL-C is unknown: 1. 2. ASCVD and LDL-C remains greater than or equal to 55 mg/dL; OR No history of ASCVD and LDL-C remains greater than or equal to 100 mg/dL. Continuation requests for Leqvio (inclisiran) may be approved when the following criteria are met: I. II. Individual continues to use in combination with maximally tolerated statin therapy (unless contraindication or individual is statin intolerant); AND Individual has achieved LDL-C reduction. Leqvio (inclisiran) may not be approved for the following: In combination with Praluent or Repatha; OR I. II. When the above criteria are not met and for all other indications. Initial Approval Duration: 1 year Continuation Approval Duration: 1 year Step Therapy Note: When a PCSK9 inhibitor is deemed approvable based on the clinical criteria above, the benefit plan may have additional criteria requiring the use of a preferred1 agent or agents. Non-Preferred PCSK9 Inhibitor Step Therapy A list of the preferred PCSK9 inhibitor agents is available here. Requests for a non-preferred PCSK9 inhibitor may be approved if the following criteria are met: I. Individual has had an adequate trial and titration of a preferred PCSK9 inhibitor and achieved suboptimal lipid lowering response despite at least 90 days of compliant therapy. 1Preferred, as used herein, refers to agents that were deemed to be clinically comparable to other agents in the same class or disease category but are preferred based upon clinical evidence and cost effectiveness. Quantity Limits Leqvio (inclisiran) Quantity Limit Leqvio (inclisiran) 284 mg/1.5 mL prefilled syringe 1 syringe per 6 months Drug Limit Initiation of therapy: May approve one additional prefilled syringe within the first six months of initiating therapy. Override Criteria Coding The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member. HCPCS J1306 ICD-10 Diagnosis Injection, inclisiran, 1 mg [Leqvio] I25.10-I25.812 Atherosclerosis and atherosclerotic heart disease 3 I20.8 I20.9 I23.7 I24.0-I24.8 I25.2-I25.9 Other forms of angina pectoris Angina pectoris, unspecified Postinfarction angina Acute coronary thrombosis not resulting in myocardial infarction Coronary artery aneurysm Document history Revised: 11/17/2023