Clinical Policy: (Praluent) Reference Number: CP.CPA.268 Effective Date: 11.16.16 Last Review Date: 11.17 Line of Business: Commercial Revision Log See Important Reminder at the end of this policy for important regulatory and legal information. Description (Praluent ) is a human monoclonal antibody (IgG1 isotype) that targets proprotein convertase subtilisin kexin type 9 (PCSK9). FDA Approved Indication Praluent is indicated as adjunctive therapy to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease (ASCVD), who require additional lowering of LDL-cholesterol. Limitations of Use: The effect of Praluent on cardiovascular morbidity and mortality has not been determined. Policy/Criteria Provider must submit documentation (which may include office chart notes and lab results) supporting that member has met all approval criteria It is the policy of health plans affiliated with Centene Corporation that Praluent is medically necessary when the following criteria are met: I. Initial Approval Criteria A. Hypercholesterolemia (must meet all): 1. Diagnosis of one of the following: a. Heterozygous Familial Hypercholesterolemia based on documentation (e.g., medical records, chart notes, laboratory values) of recent LDL level (within the last 30 days) suggestive of familial hypercholesterolemia (e.g., Adults: baseline LDL >190 mg/dl; Children less than 16 years of age: baseline LDL >155 mg/dl); b. Hypercholesterolemia with history of clinical atherosclerotic cardiovascular disease defined as (i and ii): i. LDL>100 mg/dl (within the last 30 days); ii. Documented history of one of the following: a) Acute coronary syndromes; b) Myocardial Infarction; c) Stable or unstable angina; d) Coronary or other arterial revascularization (e.g., percutaneous coronary intervention or coronary artery bypass graft surgery); Page 1 of 7
e) Stroke; f) Peripheral artery disease presumed to be of atherosclerotic origin; g) Transient ischemic attack (TIA); h) Clinically significant coronary heart disease (CHD) diagnosed by invasive or noninvasive testing (such as coronary angiography, stress test using treadmill, stress echocardiography, or nuclear imaging); i) Carotid artery occlusion >50% without symptoms; j) Renal artery stenosis or renal artery stent procedure; 2. Prescribed by or in consultation with a Cardiologist, Endocrinologist, or lipid specialist; 3. One of the following (a, b or c): a. Documentation of concomitant therapy with ezetimibe (Zetia) in combination with high intensity statin therapy (atorvastatin 40 mg or Crestor 20 mg or greater) or Vytorin at simvastatin doses of at least 40 mg for a minimum of two months with demonstrated adherence; b. Clinically significant adverse effects to atorvastatin ( 40 mg), Crestor ( 20 mg) and documentation of concomitant therapy with ezetimibe (Zetia) in combination with maximally tolerated statin therapy [see Appendix B] for a minimum of two months with demonstrated adherence; c. For patients not on statin therapy (statin intolerant) both of the following (i and ii): i. Documentation of current therapy with ezetimibe (Zetia); ii. Documentation of one of the following: a) Statin re-challenge with at least the lowest dose of at least two of the following: pravastatin 10 mg, fluvastatin 20 mg, or rosuvastatin 5 mg, [see Appendix B] and at least intermittent or alternate dosing frequency (e.g., 1 to 3 times weekly) has been attempted; b) History of rhabdomyolysis; c) History of two consecutive abnormal liver function tests (LFT) greater than three times the upper limit of normal (ULN) and experienced symptoms suggesting hepatotoxicity (e.g., jaundice, dark-colored urine, light or clay-colored stools) while taking statin; 4. Dose does not exceed 150 mg every 2 weeks. Approval duration: 6 months B. Other diagnoses/indications 1. Refer to CP.CPA.09 if diagnosis is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) II. Continued Therapy A. Hypercholesterolemia (must meet all): 1. Currently receiving medication via a health plan affiliated with Centene Corporation or member has previously met initial approval criteria; 2. Documentation of recent LDL reduction (within the last 30 days) while on PCSK9 therapy (defined as at least 25% LDL reduction from baseline or LDL<70mg/dL for high risk patients or LDL <100mg/DL for medium risk patients); Page 2 of 7
3. Confirmation of continued ezetimibe (Zetia) therapy; 4. If statin tolerant, confirmation of continued statin therapy at the maximally tolerated dose with demonstrated adherence; 5. If request is for a dose increase, new dose does not exceed 150 mg every 2 weeks. Approval duration: 6 months or member s renewal period, whichever is longer B. Other diagnoses/indications (must meet 1 or 2): 1. Currently receiving medication via a health plan affiliated with Centene Corporation and documentation supports positive response to therapy. Approval duration: Duration of request or 12 months (whichever is less); or 2. Refer to CP.CPA.09 if diagnosis is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) III. Diagnoses/Indications for which coverage is NOT authorized: A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off-label use policy CP.CPA.09 or evidence of coverage documents IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key PCSK9: Proprotein convertase subtilisin/kexin type 9 (PCSK9) ASCVD: clinical atherosclerotic cardiovascular disease LFT: lipid function tests LDL: low-density lipoprotein ULN: upper limit of normal TIA: transient ischemic attack CHD: coronary heart disease ACC: American College of Cardiology AHA: American Heart Association CK: creatine kinase FDA: Food and Drug Administration Appendix B: General Information FDA advisory briefing documents discuss the questionable determination of statin intolerance, stating: many patients who are not able to take statins are not truly intolerant of the pharmacological class. As demonstrated in this program (ODYSSEY- ALTERNATIVE), when patients who met what was thought to be a rigorous clinical definition of statin intolerance were randomly assigned to receive atorvastatin 20 mg daily in a blinded fashion, 70% completed a 24-week trial. Preceding the randomized portion of this trial, 361 statinin tolerant patients entered a single-blind placebo run-in period, during which 23 (49%) of 47 run-in failures discontinued because of skeletal muscle-related adverse events that occurred while taking placebo. Maximally tolerated statin dose is defined as the inability to titrate to one of the following statin dosages due to skeletal muscle or hepatic related symptoms, concomitant medications, or medical conditions: rosuvastatin 20 mg, atorvastatin 40 mg, simvastatin 40 mg. The 2013 ACC/AHA treatment guidelines include the following conditions as clinical ASCVD: acute coronary syndromes, history of MI, stable or unstable angina, coronary or other arterial revascularization, stroke, TIA, or peripheral arterial disease presumed to be of atherosclerotic origin. Page 3 of 7
Baseline LDL prior to lipid lowering therapy should be used to satisfy the diagnostic criteria for Familial Hypercholesterolemia. Patients should remain on concomitant therapy with a statin if tolerated due to the established long term cardiovascular benefits. Patients with high risk of ASCVD include the following: o History of clinical atherosclerotic cardiovascular disease (as defined in section II) o Diabetes with an estimated 10-year ASCVD risk 7.5% for adults 40-75 years of age o Untreated LDL 190 mg/dl Patients with moderate risk of ASCVD include the following: o Diabetes with an estimated 10-year ASCVD risk <7.5% for adults 40-75 years of age o Estimated 10-year ASCVD risk 5% for adults 40-75 years of age The calculator for the 10-year ASCVD risk estimator can be found here: http://tools.cardiosource.org/ascvd-risk-estimator/. Information needed to complete the ASCVD Risk Estimator include: gender, race (white, African American, other), systolic blood pressure, diabetes, age, total cholesterol, HDL-Cholesterol, treatment for hypertension, current smoker Statin re-challenge should be performed with pravastatin, fluvastatin or rosuvastatin due to their hydrophilicity which appear to produce less intrinsic muscle toxicity and fewer drug interactions compared to other statins. Re-challenge requires slow titration with lower intensity statins to titrate up to the patient s maximally tolerated statin dose with the goal of high-intensity statin use. According to the 2013 AHA/ACC lipid guidelines, rhabdomyolysis is a very rare condition. In adults selected for participation in clinical trials of statin therapy, rhabdomyolysis occurred rarely (<0.06% over a mean 4.8 to 5.1 year treatment period). If rhabdomyolysis occurs, documentation via creatine kinase (CK) levels above >10x ULN is required. Appendix C: Therapeutic Alternatives Drug Dosing Regimen Dose Limit/ Maximum Dose Ezetimibe/simvastatin (Vytorin) 10/40 mg PO QD 10/40 mg PO QD (Use of the 10/80 mg dose is restricted to patients who have been taking simvastatin 80 mg for 12 months or more without evidence of muscle toxicity) 40 mg PO QD 80 mg PO QD Atorvastatin (Lipitor) Rosuvastatin (Crestor) 5-40 mg PO QD 40 mg PO QD Repatha 140 mg SC Q2 weeks or 420 mg SC 420 mg once monthly (evolocumab) once monthly Therapeutic alternatives are listed as Brand name (generic) when the drug is available by brand name only and generic (Brand name ) when the drug is available by both brand and generic. Page 4 of 7
V. Dosage and Administration Indication Dosing Regimen Maximum Dose Heterozygous Familial Hypercholesterolemia; Hypercholesterolemia 75 mg SC once every 2 weeks or 300 mg every 4 weeks 150 mg every 2 weeks If response to 75 mg every 2 weeks or 300 mg every 4 weeks is inadequate, dose may be increased to 150 mg every 2 weeks VI. Product Availability Single-use pre-filled pen, syringe: 75 mg/ml, 150 mg/ml VII. References 1. Food and Drug Administration Center for Drug Evaluation and Research: The Endocrinology and Metabolic Drugs Advisory Committee Meeting Briefing Document BLA 125559 Praluent (alirocumab) injection. June 9, 2015. Available at: http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/ EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM449865.pdf. Accessed: June 9, 2015. 2. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 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 June 24; 129[suppl 2]: S1-S45. 3. Moriarty PM, Jacobsen 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. 4. Praluent [Prescribing Information]. Bridgewater, NJ; Sanofi Aventis and Regeneron Pharmaceuticals: April 2017. 5. Hopkins PN, Toth PP, Ballantyne CM, et al. Familial Hypercholesterolemias: Prevalence, genetics, diagnosis and screening recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. Journal of Clinical Lipidology. 2011. 5; S9- S17. 6. Joy TR & Hegele RA, et al. Narrative review: statin-related myopathy. Ann Intern Med. 2009;150(12):858.http://www.ncbi.nlm.nih.gov/pubmed?term=19528564. Accessed May 11, 2016. 7. Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PWF. 2013 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. 2013;00:000 000. Page 5 of 7
Reviews, Revisions, and Approvals Date P&T Approval Date Converted to new template. Minor changes to verbiage and grammar. References updated. 06.12.17 11.17 Important Reminder This clinical policy has been developed by appropriately experienced and licensed health care professionals based on a review and consideration of currently available generally accepted standards of medical practice; peer-reviewed medical literature; government agency/program approval status; evidence-based guidelines and positions of leading national health professional organizations; views of physicians practicing in relevant clinical areas affected by this clinical policy; and other available clinical information. The Health Plan makes no representations and accepts no liability with respect to the content of any external information used or relied upon in developing this clinical policy. This clinical policy is consistent with standards of medical practice current at the time that this clinical policy was approved. Health Plan means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan s affiliates, as applicable. The purpose of this clinical policy is to provide a guide to medical necessity, which is a component of the guidelines used to assist in making coverage decisions and administering benefits. It does not constitute a contract or guarantee regarding payment or results. Coverage decisions and the administration of benefits are subject to all terms, conditions, exclusions and limitations of the coverage documents (e.g., evidence of coverage, certificate of coverage, policy, contract of insurance, etc.), as well as to state and federal requirements and applicable Health Plan-level administrative policies and procedures. This clinical policy is effective as of the date determined by the Health Plan. The date of posting may not be the effective date of this clinical policy. This clinical policy may be subject to applicable legal and regulatory requirements relating to provider notification. If there is a discrepancy between the effective date of this clinical policy and any applicable legal or regulatory requirement, the requirements of law and regulation shall govern. The Health Plan retains the right to change, amend or withdraw this clinical policy, and additional clinical policies may be developed and adopted as needed, at any time. This clinical policy does not constitute medical advice, medical treatment or medical care. It is not intended to dictate to providers how to practice medicine. Providers are expected to exercise professional medical judgment in providing the most appropriate care, and are solely responsible for the medical advice and treatment of members. This clinical policy is not intended to recommend treatment for members. Members should consult with their treating physician in connection with diagnosis and treatment decisions. Providers referred to in this clinical policy are independent contractors who exercise independent judgment and over whom the Health Plan has no control or right of control. Providers are not agents or employees of the Health Plan. Page 6 of 7
This clinical policy is the property of the Health Plan. Unauthorized copying, use, and distribution of this clinical policy or any information contained herein are strictly prohibited. Providers, members and their representatives are bound to the terms and conditions expressed herein through the terms of their contracts. Where no such contract exists, providers, members and their representatives agree to be bound by such terms and conditions by providing services to members and/or submitting claims for payment for such services. 2016 Centene Corporation. All rights reserved. All materials are exclusively owned by Centene Corporation and are protected by United States copyright law and international copyright law. No part of this publication may be reproduced, copied, modified, distributed, displayed, stored in a retrieval system, transmitted in any form or by any means, or otherwise published without the prior written permission of Centene Corporation. You may not alter or remove any trademark, copyright or other notice contained herein. Centene and Centene Corporation are registered trademarks exclusively owned by Centene Corporation. Page 7 of 7