Praluent (alirocumab)

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1 Praluent (alirocumab) Policy Number: Last Review: 06/2018 Origination: 07/2015 Next Review: 06/2019 Policy Blue Cross and Blue Shield of Kansas City (Blue KC) will provide coverage for Praluent when it is determined to be medically necessary because the criteria listed below are met. When Policy Topic is covered Food and Drug Administration (FDA)-Approved Indications 1. Heterozygous Familial Hypercholesterolemia [HeFH]. * Approve Praluent for 12 months if the patient meets the following criteria (A, B, C, D and E): A) The patient is aged 18 years; AND B) The patient has an LDL-C level 160 mg/dl (after treatment with antihyperlipidemic agents but prior to PCSK9 inhibitor therapy such as Praluent or Repatha) [documentation required]; AND C) The patient meets one of the following criteria (i or ii): i. The patient has tried at least 2 statins with at least one being a high-intensity statin therapy (i.e., atorvastatin 40 mg daily; Crestor 20 mg daily [as a single-entity or as a combination product]) * AND Zetia (ezetimibe tablets) [as a single-entity or as a combination product] concomitantly for 8 continuous weeks [documentation required]; AND the LDL-C level remains 70 mg/dl [documentation required]; OR ii. The patient has been determined to be statin intolerant by meeting one of the following criteria (a or b): a) The patient experienced statin-related rhabdomyolysis (statin-induced muscle breakdown with signs and symptoms such as muscle pain, weakness, tenderness, acute renal failure and/or elevated creatine kinase [CK] levels [e.g., 10 times the upper limit of normal]) [documentation required]; OR b) The patient experienced skeletal-related muscle symptoms (e.g., myopathy [muscle weakness] or myalgia [muscle aches, soreness, stiffness, or tenderness]) and meets both of the following criteria [(1) and (2)]: (1) The skeletal-related muscle symptoms (e.g., myopathy or myalgia) occurred while receiving separate trials of both atorvastatin and Crestor (as single-entity or as combination products) [documentation required]; AND (2) When receiving separate trials of both atorvastatin and Crestor (as singleentity or as combination products) the skeletal-related muscle symptoms (e.g., myopathy, myalgia) resolved upon discontinuation of each respective statin therapy (atorvastatin and Crestor); AND D) Praluent is prescribed by, or in consultation with, a cardiologist; an endocrinologist; or a physician who focuses in the treatment of cardiovascular (CV) risk management and/or lipid disorders; AND E) If able to tolerate statins, the patient continues to receive the maximum tolerated dose of a statin while receiving Praluent therapy.

2 2. Hyperlipidemia in Patients with Clinical Atherosclerotic Cardiovascular Disease (ASCVD). * Approve Praluent for 12 months if the patient meets the following criteria (A, B, C, D and E): A) The patient is aged 18 years; AND B) The patient meets the following criteria (i and ii): i. The patient has an LDL-C level 70 mg/dl (after treatment with antihyperlipidemic agents but prior to PCSK9 inhibitor therapy such as Praluent or Repatha) [documentation required]; AND ii. The patient has had one of the following conditions or diagnoses (a, b, c, d, or e): a) The patient has had a previous myocardial infarction (MI) or has a history of an acute coronary syndrome (ACS); OR b) The patient has a diagnosis of angina (stable or unstable); OR c) The patient has a past history of stroke or transient ischemic attack (TIA); OR d) The patient has peripheral arterial disease (PAD); OR e) The patient has undergone a coronary or other arterial revascularization procedure in the past; AND C) The patient meets one of the following criteria (i or ii): i. The patient has tried at least 2 statins with at least one being a high-intensity statin therapy (i.e., atorvastatin 40 mg daily; Crestor 20 mg daily [as a single-entity or as a combination product]) * AND Zetia (ezetimibe tablets) [as a single-entity or as a combination product] concomitantly for 8 continuous weeks [documentation required]; AND the LDL-C level remains 70 mg/dl [documentation required]; OR ii. The patient has been determined to be statin intolerant by meeting one of the following criteria (a or b): a) The patient experienced statin-related rhabdomyolysis (statin-induced muscle breakdown with signs and symptoms such as muscle pain, weakness, tenderness, acute renal failure and/or elevated creatine kinase [CK] levels [e.g., 10 times the upper limit of normal]) [documentation required]; OR b) The patient experienced skeletal-related muscle symptoms (e.g., myopathy [muscle weakness] or myalgia [muscle aches, soreness, stiffness, or tenderness]) and meets both of the following criteria [(1) and (2)]: (1) The skeletal-related muscle symptoms (e.g., myopathy or myalgia) occurred while receiving separate trials of both atorvastatin and Crestor (as single-entity or as combination products) [documentation required]; AND (2) When receiving separate trials of both atorvastatin and Crestor (as singleentity or as combination products) the skeletal-related muscle symptoms (e.g., myopathy, myalgia) resolved upon discontinuation of each respective statin therapy (atorvastatin and Crestor); AND D) Praluent is prescribed by, or in consultation with, a cardiologist; an endocrinologist; or a physician who focuses in the treatment of cardiovascular (CV) risk management and/or lipid disorders; AND E) If able to tolerate statins, the patient continues to receive the maximum tolerated dose of a statin while receiving Praluent therapy. * Note: The number of drug-drug interactions that are categorized as severe or as unmodifiable by using lower doses or alternating to another statins or medications to manage the condition are limited. Exceptions based on current use of these other medications are not intentionally provided for in this policy. Praluent is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with HeFH or clinical ASCVD, who require additional LDL-C lowering. 1 In this criteria, ASCVD was defined according to that described in the 2013 ACC/AHA guidelines for the treatment of blood cholesterol. Statins are well-established therapies and should be utilized first-line in all eligible patients with elevated LDL-C levels for patients without contraindications for use who are able to tolerate these

3 agents. Data with statins, as well as Zetia added to a statin, have noted reductions in CV events. 9,18-21 At this time, CV outcomes data are not available with Praluent. Patients with ASCVD or HeFH are recommended to utilize maximally tolerated high-intensity therapy (atorvastatin 40 mg daily; Crestor 20 mg daily) first-line, along with Zetia, prior to Praluent therapy. The recently published IMPROVE-IT trial with Zetia demonstrated a reduction in CV events when Zetia was added to statin therapy (simvastatin) compared with simvastatin monotherapy in patients who had been recently hospitalized for an ACS event. As in the Praluent clinical trials and as recommended in the Praluent prescribing information, patients should continue to receive the maximally tolerated dose of statin to continue to receive the benefits established regarding CV event reduction. Use of Praluent should be judicious and under the guidance of a specialist physician (cardiologist, endocrinologist, or a physician who focuses in the treatment of CV risk management and/or lipid disorders) to assure other lipid lowering therapies have been maximized and to promote safe use of Praluent. The criteria also recognize situations in which patients are unable to take statin therapy (i.e., muscle related AEs) and that rechallenge with a different statin in such scenarios can lead to successful treatment with statin therapy. However, rhabdomyolysis, albeit rare, is a serious event and patients should not be rechallenged with statin therapy. The criteria were developed based on nationally-recognized guidelines regarding lipid management, clinical data for Praluent and other antihyperlipidemic therapies (e.g., statins, Zetia) as well as the professional opinion of specialized physicians. When Policy Topic is not covered Praluent has not been shown to be effective, or there are limited or preliminary data or potential safety concerns that are not supportive of general approval for the following conditions. Rationale for noncoverage for these specific conditions is provided below. (Note: This is not an exhaustive list of Conditions Not Recommended for Approval.) 1. Concurrent use of Praluent with Juxtapid (lomitapide capsules) or Kynamro (mipomersen injection). Both of these agents are indicated as an adjunct to lipid-lowering medications and diet to modify lipid parameters (e.g., reduce LDL-C levels) in patients with homozygous familial hypercholesterolemia (HoFH) The efficacy and safety of using these medication regimens in combination with Praluent have not been established. 2. Coverage is not recommended for circumstances not listed in the Recommended Authorization Criteria. Criteria will be updated as new published data are available. Considerations Prior authorization is recommended for prescription benefit coverage of Praluent. Although Praluent lowers LDL-C and could possibly be used in a variety of patients with hyperlipidemia, the most benefit with Praluent is noted among patients in conditions for which it is indicated (adults with HeFH or ASCVD). The intent of this policy is to recommend coverage in such patients who are likely to benefit from Praluent if LDL-C remains elevated after trial of other proven therapies (i.e., high-dose statins, Zetia). Because of the specialized skills required for evaluation and monitoring of this new therapy, approval requires Praluent to be prescribed by or in consultation with a physician who specializes in the condition being treated. All approvals are provided for 12 months in duration. Documentation: For the Comprehensive Program, documentation will be required where noted in the criteria as [documentation required]. Documentation may include, but is not limited to, chart notes, prescription claims records, prescription receipts and/or laboratory data. Description of Procedure or Service Praluent, a proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor, is indicated 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). 1 A limitation of use is that the effects of Praluent on cardiovascular (CV) morbidity and mortality has not been determined. The

4 recommended starting dose of Praluent is 75 mg administered subcutaneously (SC) once every 2 weeks (Q2W), since most patients achieve adequate LDL-C reduction with this dose. If the LDL-C response is inadequate, the Praluent dose may be increased to a maximum of 150 mg SC Q2W. It is recommended to assess LDL-C levels within 4 to 8 weeks of initiating or titrating Praluent to evaluate for response and adjust the dose, if needed. The most common adverse events (AEs) in patients treated with Praluent were nasopharyngitis (11.3%), injection site reactions (7.2%), and influenza (5.7%). AEs led to discontinuation of treatment in 5.3% of patients treated with Praluent. Rationale Clinical Data The efficacy of Praluent was assessed in several studies. 1 The Praluent prescribing information details five double-blind, placebo-controlled trials that enrolled 3,499 patients. In total, 36% of patients had HeFH and 54% of patients had clinical ASCVD (without familial hypercholesterolemia [FH]). Three of the five trials involved patients only with HeFH. Patients were receiving statin therapy at a maximally tolerated dose, with or without other lipid modifying therapies. All trials were at least 52 weeks in duration. The primary efficacy endpoint was the mean percent change in LDL-C from baseline which was assessed at Week 24. Three studies used an initial Praluent dose of 75 mg SC Q2W, followed by a potential dose increase to 150 mg SC Q2W at Week 12 for patients who did not achieve the predefined target LDL-C at Week 8. Two studies used only the Praluent 150 mg SC Q2W dose. 1 ODYSSEY LONG-TERM was a multicenter, double-blind, placebo-controlled trial that randomized patients to Praluent 150 mg SC Q2W (n = 1,553) or to placebo (n = 788). 1-2 The baseline LDL-C was 122 mg/dl. At Week 24, the treatment difference between Praluent and placebo in the mean LDL-C percent change was -58%. 1-2 ODYSSEY COMBO I study was a multicenter, double-blind, placebocontrolled trial that randomized patients to Praluent (n = 209) or placebo (n = 107). 1,3 The mean baseline LDL-C was 102 mg/dl. At Week 12, the mean percent change from baseline in LDL-C -45% with Praluent compared with 1% with placebo, and the treatment difference between Praluent 75 mg SC Q2W and placebo in the mean LDL-C percent change was -46%. 1,3 At Week 12, if additional LDL- C lowering was required based on pre-specified LDL-C criteria, the Praluent dose was increased to 150 mg SC Q2W for the remainder of the trial. At Week 24, the mean percent change from baseline in LDL-C was -44% with Praluent and -2% with placebo, and the treatment difference between Praluent and placebo in mean LDL-C percent change was -43% (P < ). The dose was increased to 150 mg SC Q2W in 17% of patients (n = 32/191) treated with Praluent for at least 12 weeks. 1 Two other multicenter, double-blind, placebo-controlled trials involved patients with HeFH who were randomized to receive Praluent (n = 490) or placebo (n = 245). The average LDL-C at baseline was 141 mg/dl. Considering both trials together, the Week 12 treatment difference between Praluent 75 mg SC Q2W and placebo in the mean LDL-C percent change was -48%. At Week 12, if additional LDL-C lowering was required, the Praluent dose was increased to 150 mg SC Q2W for the remainder of the trials. At Week 24, the mean treatment difference between Praluent and placebo in the mean LDL-C percent change from baseline was -54% (P < ). The Praluent dose was increased to 150 mg SC Q2W in 42% of patients (n = 196/469) treated with Praluent for at least 12 weeks. The LDL-C lowering effect was sustained during the trial. 1 ODYSSEY HIGH FH was a multicenter, double-blind, placebocontrolled trial that randomized patients with HeFH with a baseline LDL-C 160 mg/dl to receive Praluent 150 mg SC Q2W (n = 72) or placebo (n = 35). 1,4 The average LDL-C at baseline was 198 mg/dl. At Week 24, the mean percent change from baseline in LDL-C was -43% with Praluent and - 7% with placebo; the treatment difference between Praluent and placebo in the mean LDL-C percent change was -36% (P < ). Guidelines Praluent has not yet been addressed in clinical guidelines. Many guidelines are available regarding the treatment of patients with dyslipidemia. Two nationally recognized organizations (the American College of Cardiology [ACC]/American Heart Association [AHA] and the National Lipid Association [NLA]) have guidelines regarding the management of patients with elevated cholesterol and related conditions which are detailed below.

5 ACC/AHA Treatment of Blood Cholesterol to Reduce Atherosclerotic CV Risk in Adults In 2013, the ACC/AHA published guidelines on the treatment of blood cholesterol to reduce atherosclerotic CV risk in adults. 5 The guidelines state that many randomized controlled trials have demonstrated a consistent reduction in ASCVD events with use of statins in both primary and secondary prevention among populations most likely to benefit. The ACC/AHA guidelines identify four major groups who should be treated with an appropriate statin-intensive therapy. These groups include: 1) patients with clinical ASCVD, which includes patients with a past acute coronary syndrome (ACS), or history of a myocardial infarction (MI), stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack (TIA), or peripheral arterial disease (PAD) presumed to be atherosclerotic origin; 2) patients with primary elevations of LDL-C 190 mg/dl; 3) patients 40 to 75 years of age with diabetes and an LDL-C between 70 and 189 mg/dl (without ASCVD); and 4) patients without clinical ASCVD or diabetes with an LDL-C between 70 and 189 mg/dl, and have an estimated 10-year ASCVD risk 7.5%. The ACC/AHA guidelines emphasize the appropriate intensity of statin therapy to reduce CV risk in patients who will benefit. 5 No statin is preferred, but instead, statins with related doses are categorized as high-intensity (lowers LDL-C by approximately 50%), moderate-intensity (lowers LDL-C by approximately 30% to < 50%), and low-intensity (lowers LDL-C by < 30%). Only atorvastatin and Crestor (rosuvastatin tablets) are categorized as high-intensity statin therapy, which is recommended for many patient populations at high CV risk. Table 1 categorizes the different statin regimens as high-, moderate-, and low-intensity. Refer to the guideline for the most appropriate intensity for the individual patient. These guidelines do not focus on LDL-C goals but emphasize the benefits of LDL-C reduction. Evidence from randomized controlled trials demonstrates that ASCVD events are reduced when patients use the maximum tolerated statin intensity in the groups in which benefits have been demonstrated. Table 1. High-, Moderate-, and Low-Intensity Statin Therapy. 5* High-Intensity Statin Therapy Moderate-Intensity Statin Therapy Low-Intensity Statin Therapy Daily dose lowers LDL-C on average by approximately 50%. Daily dose lowers LDL-C on average by approximately 30% to < 50%. Daily dose lowers LDL-C on average by < 30%. Atorvastatin (40 mg ) to 80 mg Crestor 20 mg (40 mg) Atorvastatin 10 mg (20 mg) Crestor (5 mg) 10 mg Simvastatin 20 mg to 40 mg Pravastatin 40 mg (80 mg) Lovastatin 40 mg Lescol XL 80 mg Fluvastatin 40 mg BID Livalo 2 mg to 4 mg Simvastatin 10 mg Pravastatin 10 mg to 20 mg Lovastatin 20 mg Fluvastatin 20 mg to 40 mg Livalo 1 mg * Individual responses to statin therapy varied in the randomized controlled trials and should be expected to vary in clinical practice. There might be a biologic basis for a less-than-average response; Specific statins and doses are bolded that were evaluated in randomized controlled trials in which a major reduction in cardiovascular events was demonstrated. Statins and doses that are approved by the Food and Drug Administration but were not tested in randomized controlled trials are in italics; LDL- C Low-density lipoprotein cholesterol; Evidence from one randomized controlled trial only and down titration is recommended if the patient is unable to tolerate atorvastatin 80 mg; Although simvastatin 80 mg was assessed in randomized controlled trials, initiation of simvastatin 80 mg or titration to 80 mg is not recommended by the Food and Drug Administration due to the increased risk of myopathy, including rhabdomyolysis; BID Twice daily.

6 NLA Management of Dyslipidemia In 2014, the NLA published recommendations for patient-centered management of dyslipidemia. 6-7 The guidelines recommend treatment goals. Regarding LDL-C, patients at low, moderate, or high risk are recommended to obtain an LDL-C level < 100 mg/dl. Patients at very high risk are recommended to achieve an LDL-C level < 70 mg/dl. Patients with ASCVD are included among the patients defined as being very high risk. Patients at high risk include those with an LDL-C 190 mg/dl, which suggests that patients may have FH. Unless contraindicated, first-line drug therapy for the treatment of disorders involving dyslipidemia includes a moderate- or high-intensity statin. High-intensity statin therapy includes atorvastatin (40 to 80 mg once daily [QD]) or Crestor (20 to 40 mg QD), which leads to an LDL-C reduction of 50%. The guidelines also note that one risk indicator also includes patients with an LDL-C 160 mg/dl. NLA Familial Hypercholesterolemia In 2011, the NLA published guidelines for the screening, diagnosis, and management of pediatric and adult patients with FH. 8 FH encompass a group of genetic defects that cause severe elevations in LDL- C levels, as well as other lipid parameters. HeFH occurs in approximately 1 in 300 to 500 patients and is present in childhood. Total cholesterol (total-c) levels in HeFH range from 350 to 550 mg/dl, which can result in premature ASCVD. Aggressive lipid-lowering therapy is recommended to achieve LDL-C reductions of at least 50%. Both children and adults with LDL-C levels 190 mg/dl following lifestyle modifications will require medication therapy. Statins are the initial treatment for all adults with FH. Higher risk patients may require intensification of drug therapy to achieve the more aggressive treatment goals. Intensification of medication therapy should be considered if LDL-C remains 160 mg/dl or if an initial 50% reduction in LDL-C is not achieved. Other Lipid-Lowering Therapies The ACC/AHA guidelines note that there is substantially less evidence for non-statin medications in reducing ASCVD risk. 5 However, the guidelines became available prior to publication of the IMPROVE- IT trial (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) with Zetia (ezetimibe tablets). 9 The trial involved patients (n = 18,144) who had been hospitalized for an ACS within the last 10 days; the mean LDL-C at baseline was 93.8 mg/dl. Patients receiving standard therapy for the treatment of ACS were also randomized in a double-blind manner to receive Zetia 10 mg QD plus simvastatin 40 mg QD or simvastatin 40 mg QD. The median follow-up was 6 years. The median timeweighted average LDL-C level during the trial was 53.7 mg/dl in the Zetia plus simvastatin 40 mg group compared with 69.5 mg/dl in the simvastatin 40 mg monotherapy group (P < 0.001). The Kaplan-Meier event rate for the primary endpoint at 7 years (composite of CV death, nonfatal MI, unstable angina requiring rehospitalization, coronary revascularization [ 30 days after randomization] or nonfatal stroke) was 32.7% with Zetia plus simvastatin 40 mg QD vs. 34.7% with simvastatin 40 mg QD (P = 0.016). 9 Of note, adding Zetia to statins leads to additional decreases of LDL-C by up to - 25% The NLA guidelines for the management of dyslipidemia recommend therapy with a statin plus additional agents for those who have not achieved treatment goals for atherogeneic cholesterol levels, especially patient at very high or high risk. 6-7 Statin-Associated Adverse Events (AEs) Statins have been associated with muscle-related AEs such as myalgia (e.g., muscle aches, soreness, stiffness, or tenderness), myopathy (muscle weakness), and/or myositis (muscle inflammation). 12 Although the incidence is variable, muscle AEs are reported in around 5% of patients receiving statins, but may be due to other causes (e.g., excessive exercise, other medical conditions [hypothyroidism], non-statin medications). Rhabdomyolysis, which is uncommon with statin therapy, is a severe musclerelated AE that results in muscle breakdown and may or may not be associated with muscle-related symptoms (e.g., muscle pain, weakness, tenderness) along with acute renal failure and/or elevated creatine kinase [CK] levels. In patients with statin-related muscle AEs, symptoms may not re-occur if the patient switches to a different statin therapy.

7 In 2014 the NLA Statin Intolerance Panel published an update. 13 It was stated that most statin intolerance is due to myalgia. The strongest evidence at present for statin intolerance in a population is that myalgia appears but then remits with withdrawal, but reoccurs with rechallenge. The incidence of statin intolerance is widely variable. The Panel states that statins are among the safest medications available. The Panel does advise that due to statin benefits, it is safe to recommend a patient continue statin therapy even when some degree of statin intolerance is present, if patient can reasonably tolerate the statin. 13 A pivotal trial with Praluent called ODYSSEY ALTERNATIVE defined statin intolerance as the inability to take at least two different statins due to muscle-related AE, of which one statin was administered at the lowest approved starting dose. 14 Data also suggest that many patients who are rechallenged with statin therapy after an AE may be able to tolerate statin therapy long-term Of note, in the ODYSSEY ALTERNATIVE trial with Praluent, 69.8% of patients who were considered statin intolerant were treated with atorvastatin 20 mg QD and completed the double-blind 24-week portion of the trial. 17 This suggests that rechallenge with a statin in those purported to be statin intolerant is reasonable and may lead to successful use of a statin therapy. References 1. Praluent injection for subcutaneous use [prescribing information]. Bridgewater, NJ and Tarrytown, NY: sanofi-aventis and Regeneron Pharmaceuticals; July Robinson JG, Farnier M, Krempf M, et al, for the ODYSSEY LONG TERM Investigators. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372(16) Kereiakes DJ, Robinson JG, Cannon CP, et al. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: The ODYSSEY COMBO 1 study. Am Heart J. 2015;169; e Ginsberg HN, Rader DJ, Raal FJ, et al. ODYSSEY FH: efficacy and safety of alirocumab in patients with severe heterozygous familial hypercholesterolemia [abstract]. Circulation. 2014;130(23): Stone NJ, Robinson J, Lichtenstein AH, et al ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice guidelines. Circulation. 2014;129(25 Suppl 2):S1-S45. Available at Accessed on July 23, Jacobson TA, Ito MK, Maki KC, et al. National Lipid Association recommendations for patientcentered management of dyslipidemia: Part 1-executive summary. J Clin Lipidol. 2014;8: Available at: Accessed on July 23, Jacobson TA, Ito MK, Maki KC, et al. National Lipid Association recommendations for patientcentered management of dyslipidemia: Part 1-full report. J Clin Lipidol. 2015;9: Goldberg AC, Hopkins PN, Toth PP, et al. Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients. J Clin Lipidol. 2011;5:S1-S8. 9. Cannon CP, Blazing MA, Giugliano RP, et al, for the IMPROVE-IT investigators. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372(25): Zetia tablets [prescribing information]. Whitehouse Station, NJ: Merck; August Morrone D, Weintraub WS, both PP, et al. Lipid-altering efficacy of ezetimibe plus statin and statin monotherapy and identification of factors associated with treatment response: a pooled analysis of over 21,000 subjects from 27 clinical trials. Atherosclerosis. 2012;223(2): Rosenson RS, Baker SK, Jacobson TA, et al. An assessment by the statin muscle safety task force: 2014 update. J Clin Lipidol. 2014;8:S58-S Guyton JR, Bays HE, Grundy SM, Jacobson TA. An assessment by the Statin Intolerance Panel: 2014 update. J Clin Lipidol. 2014;8:S72-S Moriarty PM, Jacobson TA, Bruckert E, et al. Efficacy and safety of alirocumab, a monoclonal antibody to PCSK9, in statin-intolerant patients: design and rationale of ODYSSEY ALTERNATIVE, a randomized phase 3 trial. J Clin Lipidol. 2014;8:

8 15. Zhang H, Plutzky J, Skentzos S, et al. Discontinuation of statins in routine care settings. Ann Intern Med. 2013;158(7): Mampuya WM, Frid D, Rocco M, et al. Treatment strategies in patients with statin intolerance: the Cleveland Clinic Experience. Am Heart J. 2013;166(3): Praluent (alirocumab injection). Food and Drug Administration Center for Drug Evaluation and Research. The Endocrinologic and Metabolic Drugs Advisory Committee Meeting. June 9, Briefing Document. BLA Available at: ogicandmetabolicdrugsadvisorycommittee/ucm pdf. Accessed on July 23, Cholesterol Treatment Trialists (CTT) Collaborators. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012;380: Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev Jan 31;1:CD Cholesterol Treatment Trialists (CCT) Collaborators, Kearney PM, Blackwell L, Collins R, et al. Efficacy of cholesterol lowering therapy in 18,686 people with diabetes in 14 randomized trials: a meta-analysis. Lancet. 2008;371(9607) Baigent C, Keech A, Kearney PM, et al, for the Cholesterol Treatment Trialists (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomized trials of statins. Lancet. 2005;366(9493): Kynamro solution for subcutaneous injection [prescribing information]. Cambridge, MA: Genzyme; March Juxtapid capsules [prescribing information]. Cambridge, MA: Aegerion Pharmaceuticals; August Billing Coding/Physician Documentation Information Praluent is a pharmacy benefit Additional Policy Key Words ; Repatha Policy Implementation/Update Information 07/2015 New policy titled Praluent (alirocumab) 07/2016 Annual review- no changes to policy statement 07/2017 Annual review- no changes to policy statement 06/2018 Annual review- no changes to policy statement State and Federal mandates and health plan contract language, including specific provisions/exclusions, take precedence over Medical Policy and must be considered first in determining eligibility for coverage. The medical policies contained herein are for informational purposes. The medical policies do not constitute medical advice or medical care. Treating health care providers are independent contractors and are neither employees nor agents Blue KC and are solely responsible for diagnosis, treatment and medical advice. No part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by any means, electronic, photocopying, or otherwise, without permission from Blue KC.