Drug Therapy Guidelines

Transcription

1 Drug Therapy Guidelines PCSK9 Inhibitors: Praluent TM, Repatha TM Applicable Medical Benefit Effective: 5/1/18 Pharmacy- Formulary 1 x Next Review: 3/19 Pharmacy- Formulary 2 x Date of Origin: 10/9/15 Pharmacy- Formulary 3/Exclusive x Review Dates: 9/15, 3/16, 3/17, 3/18 Pharmacy- Formulary 4/AON x I. Medication Description PCSK9 inhibitors are human monoclonal IgG2 antibodies that binds to and inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9) binding to low-density lipoprotein receptors (LDLR). PCSK9 binds to LDLR on the hepatocyte surface to promote LDLR degradation within the liver. LDLR is the primary receptor that clears circulating LDL; with evolocumab inhibiting the binding of PCSK9 to LDLR, the number of LDLRs available to clear LDL increases, thereby lowering LDL-C concentrations. II. Position Statement Coverage is determined through a prior authorization process with supporting clinical documentation for every request. III. Policy Coverage is available for those who meet all of the following criteria: One of the following, dependent upon the diagnosis: o For hyperlipidemia in clinical Atherosclerotic Cardiovascular Disease (ASCVD): The patient is aged 18 years AND The patient has a low-density lipoprotein cholesterol (LDL-C) level 70 mg/dl (after treatment with antihyperlipidemic agents but prior to PCSK9 inhibitor therapy) AND The patient has had one of the following conditions or diagnoses: previous myocardial infarction (MI), a history of acute coronary syndrome (ACS), angina (stable or unstable), history of stroke or transient ischemic attack (TIA), peripheral arterial disease (PAD), or has undergone a coronary or other arterial revascularization procedure in the past (e.g., coronary artery bypass graft [CABG], percutaneous coronary intervention [PCI], angioplasty, coronary stent procedure) o For Heterozygous Familial Hypercholesterolemia (HeFH): The patient is aged 18 years AND The patient has a low-density lipoprotein cholesterol (LDL-C) level 160 mg/dl (after treatment with antihyperlipidemic agents but prior to PCSK9 inhibitor therapy) o For Homozygous Familial Hypercholesterolemia (HoFH): Repatha is the prescribed medication AND The patient is aged 13 years AND The patient meets one of the following: Page 1 of 5

2 AND o The patient has genetic confirmation of two mutant alleles at the lowdensity lipoprotein receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin kexin type 9 (PCSK9) or low-density lipoprotein receptor adaptor protein 1 (LDLRAP1) gene locus OR o The patient has an untreated low-density lipoprotein (LDL-C) level > 500 mg/dl (prior to treatment with antihyperlipidemic agents) OR o The patient has a treated low-density lipoprotein cholesterol (LDL-C) level 300 mg/dl (after treatment with antihyperlipidemic agents but prior to agents such as Repatha, Kynamro [mipomersen injection] or Juxtapid [lomitapide capsules]) OR o The patient has clinical manifestations of HoFH (e.g., cutaneous xanthomas, tendon xanthomas, arcus cornea, tuberous xanthomas or xanthelasma) The medication is prescribed by (or in consultation with) a cardiologist, endocrinologist, or a physician who has obtained additional education/certification in cardiovascular risk management and/or the treatment of lipid disorders AND The patient meets one of the following: o The patient has tried one high-intensity statin therapy (atorvastatin 40 mg daily; rosuvastatin 20 mg daily) AND another antihyperlipidemic agent concomitantly for 8 continuous weeks and the LDL-C level remains 70 mg/dl OR o The patient has been determined to be statin-intolerant by meeting one of the following criteria: 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., greater or equal to 10 times the upper limit of normal]) OR 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: AND The skeletal-related muscle symptoms (e.g., myopathy or myalgia) occurred while receiving separate trials of both atorvastatin and rosuvastatin AND When receiving separate trials of both atorvastatin and rosuvastatin the skeletalrelated muscle symptoms (e.g., myopathy, myalgia) resolved upon discontinuation of each respective statin therapy If able to tolerate statins, the patient continues to receive the maximum-tolerated dose of a statin while receiving PCSK9 Inhibitor therapy IV. Quantity Limitations Coverage of Praluent will be limited to 2 pre-filled pens/syringes every 4 weeks. Coverage of Repatha will be limited to 3 pre-filled syringes/autoinjectors or one 3.5mL injector every 4 weeks. Page 2 of 5

3 V. Coverage Duration Coverage is available for 12 months and may be renewed. VI. Coverage Renewal Criteria Coverage can be renewed based upon the following criteria: Stabilization of disease or in absence of disease progression AND Absence of unacceptable toxicity from the drug VII. Billing/Coding Information Praluent is available as 75mg/mL and 150mg/mL pre-filled pens and pre-filled syringes. Repatha is available as 140mg/mL prefilled syringes, 2-pack 140mg/mL prefilled SureClick autoinjectors and 420mg/3.5mL single-use Pushtronex system (on-body infuser with prefilled cartridge). VIII. Summary of Policy Changes 10/9/15: new policy 6/15/16: no policy changes 4/5/17: package sizes updated; quantity limits updated to reflect changes in package sizes 5/1/18: no policy changes IX. References 1. Repatha injection for subcutaneous use [prescribing information]. Thousand Oaks, CA: Amgen; 7/ Praluent injection for subcutaneous use [prescribing information]. Bridgewater, NJ and Tarrytown, NY: sanofi-aventis and Regeneron Pharmaceuticals; 10/ Robinson JG, Nedergaard BS, Rogers WJ, et al, for the LAPLACE-2 Investigators. Effect of evolocumab or ezetimibe added to moderate- or high-intensity statin therapy on LDL-C lowering in patients with hypercholesterolemia. The LAPLACE-2 randomized clinical trial. JAMA. 2014;311(18): [Supplemental Appendix]. 4. Blom DJ, Hala T, Bolognese M, et al, for the DESCARTES Investigators. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. N Engl J Med. 2014;370: [Supplemental Appendix]. 5. Raal FJ, Stein EA, Dufour R, et al, for the RUTHERFORD-2 Investigators. PCSK9 inhibition with evolocumab (AMG145) in heterozygous familial hypercholesterolemia (RUTHERFORD-2): a randomized, double-blind, placebo-controlled trial. Lancet. 2015;385: [Supplemental Appendix]. 6. Raal FJ, Honarpour N, Blom DJ, et al, for the TESLA Investigators. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolemia (TESLA Part B): a randomized, double-blind, placebo-controlled trial. Lancet. 2015;385: 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 Page 3 of 5

4 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 patient-centered 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 patient-centered 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-S 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 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): 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): Cuchel M, Bruckert E, Ginsberg HN, et al, for the European Atherosclerosis Society Consensus Panel on Familial Hypercholesterolemia. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholestolaemia of the European Atherosclerosis Society. Eur Heart J. 2014;35: Zocor tablets [prescribing information]. Whitehouse Station, NJ: Merck; Revised 3/ Lipitor tablets [prescribing information]. New York, NY: Pfizer; Revised 6/ Crestor tablets [prescribing information]. Wilmington, DE: AstraZeneca; Revised 8/ Vytorin tablets [prescribing information]. Whitehouse Station, NJ: Merck; Revised 10/2016. Page 4 of 5

5 27. Liptruzet tablets [prescribing information]. Whitehouse Station, NJ: Merck; Revised 5/ Kynamro solution for subcutaneous injection [prescribing information]. Cambridge, MA: Genzyme; Revised 5/ Juxtapid capsules [prescribing information]. Cambridge, MA: Aegerion Pharmaceuticals; Revised 8/2017. The Plan fully expects that only appropriate and medically necessary services will be rendered. The Plan reserves the right to conduct pre-payment and post-payment reviews to assess the medical appropriateness of the above-referenced therapies. Drug therapy initiated with samples will not be considered as meeting medical necessity for coverage for non-preferred or prior authorized medications. The preceding policy applies only to members for whom the above named pharmacy benefit medications are included on their covered formulary. Members with closed formulary benefits are subject to trying all appropriate formulary alternatives before a coverage exception for a non-formulary agent will be considered. The preceding policy is a guideline to allow for coverage of the pertinent medication/product, and is not meant to serve as a clinical practice guideline. Page 5 of 5