Kynamro (mipomersen)

Transcription

1 Kynamro (mipomersen) Line(s) of Business: HMO; PPO; QUEST Integration Original Effective Date: 10/01/2015 Current Effective Date: 01/01/201803/01/2019 POLICY A. INDICATIONS The indications below including FDA-approved indications and compendial uses are considered a covered benefit provided that all the approval criteria are met and the member has no exclusions to the prescribed therapy. FDA-Approved Indications Kynamro is indicated as an adjunct to lipid-lowering medications and diet to reduce low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apo B), total cholesterol, and non-high density lipoprotein-cholesterol (non-hdl-c) in patients with homozygous familial hypercholesterolemia (HoFH). Homozygous familial hypercholesterolemia o An adjunct to lipid-lowering medications and diet to reduce low density lipoproteincholesterol (LDL-C), apolipoprotein B (apob), total cholesterol (TC), and non-high density lipoprotein-cholesterol (non HDL-C) in patients with homozygous familial hypercholesterolemia (HoFH) B. CRITERIA FOR INITIAL APPROVAL Homozygous familial hypercholesterolemia (HoFH) Authorization for 12 months may be granted for members who meet all of the criteria listed below: 1. Member has a diagnosis of HoFH confirmed by genetic analysis or clinical criteria (See Appendices). 2. Prior to initiation of treatment with Kynamro, patient is/was receiving a combination lipidlowering regimen consisting of a high-intensity statin, ezetimibe, and evolocumab (Repatha). 3. Prior to initiation of treatment with Kynamro, patient is/was experiencing an inadequate response to such a combination regimen, as demonstrated a treated LDL-C of greater than or equal to 100 mg/dl (or greater than or equal to 70 mg/dl with clinical atherosclerotic cardiovascular disease [ASCVD]). C. CONTINUATION OF THERAPY Authorization of 12 months may be granted for members (including new members) who meet all initial authorization criteria and have achieved or maintained a LDL-C reduction greater than 20% from the levels immediately prior to initiation of treatment with Kynamro.

2 D. DOSAGE AND ADMINISTRATION Approvals may be subject to dosing limits in accordance with FDA-approved labeling, accepted compendia, and/or evidence-based practice guidelines. E. ADMINISTRATIVE GUIDELINES Precertification is required. Please refer to the HMSA medical policy web site for the fax form. F. IMPORTANT REMINDER The purpose of this Medical Policy is to provide a guide to coverage. This Medical Policy is not intended to dictate to providers how to practice medicine. Nothing in this Medical Policy is intended to discourage or prohibit providing other medical advice or treatment deemed appropriate by the treating physician. Benefit determinations are subject to applicable member contract language. To the extent there are any conflicts between these guidelines and the contract language, the contract language will control. This Medical Policy has been developed through consideration of the medical necessity criteria under Hawaii s Patients Bill of Rights and Responsibilities Act (Hawaii Revised Statutes 432E-1.4), generally accepted standards of medical practice and review of medical literature and government approval status. HMSA has determined that services not covered under this Medical Policy will not be medically necessary under Hawaii law in most cases. If a treating physician disagrees with HMSA/CVS determination as to medical necessity in a given case, the physician may request that HMSA reconsider the application of the medical necessity criteria to the case at issue in light of any supporting documentation. G. APPENDICES APPENDIX A. Diagnosis of Homozygous Familial Hypercholesterolemia Genetic confirmation o Mutations in both alleles at LDL receptor, ApoB, PCSK9 or LDL receptor adaptor protein gene locus Clinical diagnosis o Untreated LDL-C > 500 mg/dl OR unknown untreated LDL-C with treated LDL-C > 300 mg/dl plus o One of the following: Tendon or cutaneous xanthomas at age 10 or younger Diagnosis of familial hypercholesterolemia (FH) by Simon-Broome Diagnostic Criteria or Dutch Lipid Clinic Network Criteria (See Appendix B) in both parents Evidence of FH in both parents with a history including any of the following: Total cholesterol 310 mg/dl Premature ASCVD (before 55 years in men and 60 years in women) Tendon xanthoma Sudden premature cardiac death APPENDIX B: Diagnosis of familial hypercholesterolemia (FH) A diagnosis of FH is made when one of the following diagnostic criteria is met: Genetic confirmation

3 o An LDL-receptor mutation, familial defective apo B-100, or a PCSK9 gain-of-function mutation Simon-Broome Diagnostic Criteria for FH o Total cholesterol > 290 mg/dl or LDL-C > 190 mg/dl in patients over 16 years of age or total cholesterol > 260 mg/dl or LDL-C > 155 mg/dl in patients less than 16 years of age and one of the following Tendon xanthomas in the patient, first (parent, sibling or child) or second degree relative (grandparent, uncle or aunt) Family history of myocardial infarction in a first degree relative before the age of 60 or in a second degree relative before the age of 50 Total cholesterol greater than 290 mg/dl in an adult first or second degree relative Total cholesterol greater than 260 mg/dl in a child, brother, or sister aged younger than 16 years Dutch Lipid Clinic Network Criteria for FH o Total score > 5 points H. REFERENCES 1. Kynamro [package insert]. Cambridge, MA: Genzyme Corporation, Inc.; May Nordestgaard BG, Chapman MJ, Humphries SE, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease. Consensus Statement of the European Atherosclerosis Society. Eur Heart J. 2013;34: Cuchel M, Bruckert E, Ginsberg HN, et al. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J. 2014;35: National Institute for Health and Clinical Excellence (2008). Identification and management of familial hypercholesterolaemia. NICE clinical guideline Raal JF, Santos RD, Blom DJ, et al. Mipomersen, an apolipoprotein B Synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomized, double-blind, placebo-controlled trial. Lancet. 2010;375: Goldberg AC, Hopkins PN, Toth PP, et al. Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients. Clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol. 2011;5:S1 S8. 7. Raal JF, Santos RD. Homozygous familial hypercholesterolemia: current perspectives on diagnosis and treatment. Atherosclerosis. 2012;223: Liposorber System [package insert]. New York, NY: Kaneka Pharma America, LLC. Available at Accessed: December 6, Moriarty PM. LDL-apheresis therapy: current therapeutic practice and potential future use. Future Lipidol. 2006;3: Bays HE, Jones PH, Orringer CE, et al. National Lipid Annual Summary of Clinical Lipidology J Clin Lipidol 2016; 10:S1-S Lloyd-Jones DM, Morris PB, Ballantyne CM, Birtcher KK, Daly DD Jr., DePalma SM, Minissian MB, Orringer CE, Smith SC Jr focused update of the 2016 ACC expert consensus decision pathway on the role of non-statin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: a report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol 2017;70:

4 B. REQUIRED DOCUMENTATION The following information is necessary to initiate the prior authorization review: For initial authorization o Laboratory results, chart notes, and/or documentation of genetic or molecular testing (e.g., mutations in both alleles at LDL receptor, ApoB, PCSK9, or ARH adapter protein gene locus) to support the diagnosis of HoFH o Untreated (if known) and current LDL-C level o Untreated (if known) and current triglyceride level o Previous and current treatment regimen(s) (e.g., LDL-apheresis, name of medications, total daily s) For continuation of treatment o Pretreatment and current LDL-C levels, liver function tests including ALT, AST, and bilirubin C. EXCLUSIONS For initiation of treatment o Moderate or severe hepatic impairment (e.g., Child-Pugh B or C) For continuation of treatment o ALT or AST equal to or greater than 5 times the upper limit of normal (ULN) o ALT or AST greater than 3x ULN with signs or symptoms of liver toxicity or injury, increases in bilirubin greater than 2x ULN, or active liver disease

5 D. PRESCRIBER RESTRICTIONS Prescriber must be a lipid specialist or a cardiometabolic specialist. Members who reside in areas where access to lipid specialists and cardiometabolic specialists are limited, prescriber must be a board-certified cardiologist or endocrinologist. E. CRITERIA FOR APPROVAL 1. Homozygous familial hypercholesterolemia Authorization for 12 months may be granted for members who meet ALL of the criteria listed below: 1. Member has a diagnosis of HoFH confirmed by ONE of the following: i. Documented mutations in both alleles at LDL receptor, ApoB, PCSK9, or ARH adapter protein gene locus ii. Documented skin fibroblast LDL receptor activity less than 20% of normal iii. Combination of ALL of the following a) Untreated LDL-C greater than 500 mg/dl or unknown b) Triglyceride level less than 350 mg/dl c) Tendon or cutaneous xanthomas at age 10 or younger OR both parents with a history of LDL-C greater than 190 mg/dl 2. Prior to initiation of treatment with Kynamro, member is/was receiving a combination lipid-lowering regimen consisting of at least 3 of the treatment options listed below for at least 3 months. i. Regular LDL apheresis (i.e., at least once every 2 weeks) ii. Lipid-lowering medications at s greater or equal to the s specified below Table. Lipid lowering medications Class Medication Dose Adults Statins (Highintensity statins) Children and adolescents (Age < 18 years) Crestor (rosuvastatin) 40 mg Age < 8 years: Any Age 8 to 17 years: 20 mg/day or higher Lipitor (atorvastatin) 80 mg Age < 6 years: Any Age 6-9 years: 0.2 mg/kg in 2.5 mg increment or 10 mg/day Age years: 0.2 mg/kg in 2.5 mg increment or 20 mg/day

6 Zocor (simvastatin) mg Age < 10 years: Any Age 10 to 17 years: 40 mg/day or higher Fibrates Fenoglide (fenofibrate) 120 mg Any Lipofen (fenofibrate) 150 mg Any Tricor (fenofibrate) 145 mg Any Triglide (fenofibrate) 160 mg Any Fibricor (fenofibric acid) 105 mg Any Trilipix (fenofibric acid) 135 mg Any Lopid (gemfibrozil) 1200 mg Any Bile acid sequestrants Inhibitor of intestinal cholesterol Questran or Prevalite (cholestyramine) 24 g Age < 10 years: 240 mg/kg/day or 4 g/day or higher Age years: 240 mg/kg/day or 8 g/day Welchol (colesevelam) 3.75 g Age < 10 years: Any Age years: 3.75 g/day Colestid (colestipol) 16 g Age < 8 years: Any Age 8-17 years: 10 g Zetia (ezetimibe) 10 mg Age < 8 years: Any Age 8-17 years: 10 mg Combination products* Liptruzet (ezetimibe/atorvastatin) 10 mg/80 mg See Lipitor above for age-specific requirement (Available in 10/10, 10/20, 10/40, 10/80) Vytorin (ezetimibe/simvastatin) 10 mg/80 mg See Zocor above for age-specific requirement (Available in 10/10, 10/20, 10/40, 10/80) *Combination products will be counted as two medications for the purpose of this Policy.

7 3. Prior to initiation of treatment with Kynamro, patient is/was experiencing an inadequate response to such combination regimen, as demonstrated by one of the following: i. Treated LDL-C greater than or equal to 300 mg/dl ii. Treated LDL-C greater than 200 mg/dl with a documented history of any of the following: Myocardial infarction Coronary bypass graft surgery Coronary arteriogram demonstrating significant coronary artery disease or percutaneous transluminal coronary angioplasty (PTCA) with or without atherectomy or coronary stent placement Significant angina pectoris with a positive thallium or other heart scanning stress test F. CONTINUATION OF THERAPY Authorization of 12 months may be granted for members (including new members) who meet all initial authorization criteria and have achieved or maintained a LDL-C reduction greater than 20% from the levels immediately prior to initiation of treatment with Kynamro after at least 12 months of treatment.

8 G. DOSAGE AND ADMINISTRATION Approvals may be subject to dosing limits in accordance with FDA-approved labeling, accepted compendia, and/or evidence-based practice guidelines. H. IMPORTANT REMINDER The purpose of this Medical Policy is to provide a guide to coverage. This Medical Policy is not intended to dictate to providers how to practice medicine. Nothing in this Medical Policy is intended to discourage or prohibit providing other medical advice or treatment deemed appropriate by the treating physician. Benefit determinations are subject to applicable member contract language. To the extent there are any conflicts between these guidelines and the contract language, the contract language will control. This Medical Policy has been developed through consideration of the medical necessity criteria under Hawaii s Patients Bill of Rights and Responsibilities Act (Hawaii Revised Statutes 432E-1.4), generally accepted standards of medical practice and review of medical literature and government approval status. HMSA has determined that services not covered under this Medical Policy will not be medically necessary under Hawaii law in most cases. If a treating physician disagrees with HMSA s determination as to medical necessity in a given case, the physician may request that CVS/caremark reconsider the application of the medical necessity criteria to the case at issue in light of any supporting documentation. I. REFERENCES 1. Kynamro [package insert]. Cambridge, MA: Genzyme Corporation, Inc.; January Raal JF, Santos RD, Blom DJ, et al. Mipomersen, an apolipoprotein B Synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomized, double-blind, placebo-controlled trial. Lancet. 2010;375: Goldberg AC, Hopkins PN, Toth PP, et al. Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients. Clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol. 2011;5:S1 S8. 4. World Health Organization. Familial Hypercholesterolemia, Report of a WHO Consultation. Available at: Accessed December 10, World Health Organization. Familial Hypercholesterolemia, Report of a second WHO Consultation. Available at: Accessed December 10, DeMott K, Nherera L, Shaw EJ, et al. Clinical guidelines and evidence review for familial hypercholesterolemia: the identification and management of adults and children with familial hypercholesterolaemia London: National Collaborating Centre for Primary Care and Royal College of General Practitioners. 7. Wiegman A, Hutten BA, de Groot E, et al. Efficacy and safety of statin therapy in children with familial hypercholesterolemia: a randomized controlled trial. JAMA. 2004;292(3): Raal JF, Santos RD. Homozygous familial hypercholesterolemia: current perspectives on diagnosis and treatment. Atherosclerosis. 2012;223: Liposorber System [package insert]. New York, NY: Kaneka Pharma America, LLC. Available at Accessed: December 10, 2014.

9 10. Moriarty PM. LDL-apheresis therapy: current therapeutic practice and potential future use. Future Lipidol. 2006;3: Agency for Health Research and Quality (AHRQ) Effective Healthcare Program. Update of Comparative Effectiveness of Lipid-Modifying Agents. Published online: May 16, Available at: Kavey RW, Allada V, Daniels SR, et al. Cardiovascular risk reduction in high-risk pediatric patients: a scientific statement from the American Heart Association Expert Panel on Population and Prevention Science; the Councils on Cardiovascular Disease in the Young, Epidemiology and Prevention, Nutrition, Physical Activity and Metabolism, High Blood Pressure Research, Cardiovascular Nursing, and the Kidney in Heart Disease; and the Interdisciplinary Working Group on Quality of Care and Outcomes Research: Endorsed by the American Academy of Pediatrics. Circulation. 2006;114: Stone NJ, Robinson J, Lichtenstein AH, et al ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risks in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2013 Nov 12. [Epub ahead of print] 14. Lexi-Drugs [database online]. Hudson, OH: Lexicomp, Inc. Accessed November 18, Pediatric and Neonatal Lexi-Drugs [database online]. Hudson, OH: Lexicomp, Inc. Accessed November 18, Document History 10/01/2015 Original effective date 11/2016 Annual review 11/2017 Annual review 01/2018 Revision effective date (annual review) 10/2018 Annual review- adopt CVS standard 03/01/2019 Revision effective date