Subject: Juxtapid (lomitapide) Original Effective Date: 10/30/2013 Policy Number: MCP-155 Revision Date(s): Review Date(s): 12/16/15; 6/15/2016; 3/21/2017 DISCLAIMER This Medical Policy is intended to facilitate the Utilization Management process. It expresses Molina's determination as to whether certain services or supplies are medically necessary, experimental, investigational, or cosmetic for purposes of determining appropriateness of payment. The conclusion that a particular service or supply is medically necessary does not constitute a representation or warranty that this service or supply is covered (i.e., will be paid for by Molina) for a particular member. The member's benefit plan determines coverage. Each benefit plan defines which services are covered, which are excluded, and which are subject to dollar caps or other limits. Members and their providers will need to consult the member's benefit plan to determine if there are any exclusion(s) or other benefit limitations applicable to this service or supply. If there is a discrepancy between this policy and a member's plan of benefits, the benefits plan will govern. In addition, coverage may be mandated by applicable legal requirements of a State, the Federal government or CMS for Medicare and Medicaid members. CMS's Coverage Database can be found on the CMS website. The coverage directive(s) and criteria from an existing National Coverage Determination (NCD) or Local Coverage Determination (LCD) will supersede the contents of this Molina medical coverage policy (MCP) document and provide the directive for all Medicare members. RECOMMENDATIONS/COVERAGE CRITERIA This policy addresses the use of Juxtapid (lomitapide) for the treatment of treatment of homozygous familial hypercholesterolemia. ∑ The covered FDA-approved indications are conditions that are considered medically necessary; however it is not inclusive of all conditions which may be approved by the Medical Reviewer. At the discretion of the Medical Director and on a case-by-case basis, Molina Healthcare may consider authorization of the biologic therapies addressed in this policy for members with exceptional circumstances and for members with severe disease who may fall outside of the defined criteria. ∑ Molina Healthcare reserves the right to update this policy and revise coverage criteria to include or omit any off-label condition(s) as necessary based on medical literature and clinical studies that may become available. ∑ The intent of this policy is to ensure the safe, clinically appropriate and cost effective use of Juxtapid while maintaining optimal therapeutic outcomes. ∑ Lomitapide is approved only for homozygous familial hypercholesterolemia (HoFH). There is insufficient evidence from a single uncontrolled, open-label trial of 29 HoFH patients to evaluate lomitapide effectiveness to prevent CHD events. Therefore, although lomitapide demonstrated effectiveness in reducing LDL-C levels, there is uncertainty whether this equates to reduced cardiovascular morbidity and mortality. ∑ The current safety data does not support the use of lomitapide in patients with lower CHD risk. ∑ Homozygous familial hypercholesterolemia (HoFH) patients have limited therapeutic options and there is currently limited data available to be able to suggest a place in therapy for Juxtapid®. Therefore, it is recommended that Juxtapid® remain non‐preferred and be available to the few who are unable to tolerate any preferred medications. Page 1 of 17 ∑ There are no head-to-head trials comparing lomitapide to other treatments. Therefore, there is no evidence that lomitapide is safer or more effective than other treatments for homozygous familial hypercholesterolemia, including mipomersen. FDA INDICATIONS � Juxtapid (lomitapide) is indicated as an adjunct to a low-fat diet and other lipid-lowering treatments, including LDL apheresis where available, to reduce low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), apolipoprotein B (apo B), and non-high-density lipoprotein cholesterol (non-HDL-C) in patients with homozygous familial hypercholesterolemia (HoFH). Limitations of Use • The safety and effectiveness of Juxtapid (lomitapide) have not been established in patients with hypercholesterolemia who do not have HoFH. • The effect of Juxtapid (lomitapide) on cardiovascular morbidity and mortality has not been determined. Available as: 5mg, 10mg, and 20mg tablet Approved by the FDA: December 2012 RECOMMENDATIONS/COVERAGE CRITERIA Initiation of therapy with Juxtapid (lomitapide) may be authorized for members who meet ALL of the following criteria [ALL] 1. � Prescriber specialty [BOTH] ß Board-certified clinical lipidologist (achieved certification from the American Board of Clinical Lipidology); specialist in Endocrinology, Diabetes and Metabolism; cardiologist; or hematologist ‹ According to the National Lipid Association (NLA), homozygous FH patients should always be managed by a lipid specialist. B ß Prescribed by a certified REMS provider demonstrated with supporting documentation (signed attestation) 2. � Diagnosis/Indication [ALL] ß Diagnosis of definite homozygous familial hypercholesterolemia confirmed by ONE of the following genetic testing [ONE] û Genetic testing demonstrating mutations in both alleles for LDLR (LDL receptors) û Genetic testing demonstrating gain-of-function mutations in both alleles for PCSK9 û Genetic testing demonstrating mutations in both alleles for apoB (apoprotein B) û Cellular testing demonstrating reduced LDL receptor activity in fibroblasts / lymphocytes equaling 20% or less of the normal activity NOTE: Molina Healthcare will not authorize coverage for members who do not have homozygous familial hypercholesterolemia (HoFH), such as heterozygous familial hypercholesterolemia. Page 2 of 17 ß Documented diagnosis of definite FH according to the Simon Broome criteria:C [ONE] û Adult: Cholesterol above 7.5mmol/l or LDL cholesterol above 4.9 mmol/l, or Child under 16: Cholesterol above 6.7mmol/l or LDL cholesterol above 4 mmol/l AND Tendon xanthomas in patient or a 1st degree relative (parent, sibling, child), or in a 2nd degree relative (grandparent, uncle, aunt). û DNA-based evidence of an LDL receptor mutation, familial defective apoB-100, or a PCSK9 mutation. ß Laboratory or clinically determined presence of homozygous familial hypercholesterolemia defined by the presence of at least ONE of the following clinical criteria:2 [ONE] û Documented functional mutation(s) in both LDL receptor alleles or alleles known to affect LDL receptor functionality (e.g., apo B defective mutations); or û Skin fibroblast LDL receptor activity <20% normal; or û Untreated total cholesterol >500 mg/dL and triglycerides <300 mg/dL with both parents having documented total cholesterol >250 mg/dL; or û Patients with average fasting LDL-C >300 mg/dL on maximally tolerated lipid lowering therapy as decided by the treating physician. 3. � Age/Gender/Other restrictions [ONE] ß 18 years of age or older ‹ The safety and efficacy of Juxtapid (lomitapide) in children have not been established.a,b 4. � Step/Conservative Therapy/Other condition Requirements [ONE] ß Documentation in the medical record that prior to the initiation of therapy, the member has been and will continue to follow a low-fat diet supplying < 20% of energy from fat AND other lipid-lowering therapies including: [ALL] û Low-fat diet: Prior to the initiation of Juxtapid therapy, the member has been and will continue to follow a low-fat diet supplying less than 20% of energy from fat a,b û HMG CoA reductase inhibitor (statin): Inadequate clinical response (defined as failure to reach target LDL), intolerance (refer to next criterion) or contraindication to THREE of the following HMG CoA reductase inhibitor (statin) therapy after an adherent trial at maximum therapeutic dose for at least 90 days of consecutive therapy in the past 12 months: [THREE] o pravastatin (Pravachol) 80mg daily o simvastatin (Zocor) 40mg daily o atorvastatin (Lipitor) 80mg daily o rosuvastatin (Crestor) 40mg daily OR For members intolerant to statins: Failure to reach target LDL on fenofibrate, colestipol, or other approved non-formulary LDL lowering medication o Fibrates [Gemfibrozil (Lopid), Tricor, Lofibra] o nicotinic acidD Page 3 of 17 o ezetimibe o bile acid sequestrants (Cholestyramine, Light) ‹ Refer to Appendix 1 for a list of FDA-approved lipid lowering agents û LDL-C apheresis: Failure to achieve maximum results from LDL-apheresis or are not candidates for LDL-apheresis (due to clinical reasons or proximity to treatment center)G ¶ Documentation of therapeutic failure, contraindication or intolerance to Kynamro ¶ Juxtapid (lomitapide) will be used in combination with a standard lipid lowering regimen containing a high potency statin ¶ Juxtapid (lomitapide) will not be used concomitantly with mipomersen (Kynamro) ‹ The safety and effectiveness of lomitapide have not been studied in combination with mipomersen. 5. � Contraindications/Exclusions to Juxtapid (lomitapide) therapy [ANY] Authorization will not be granted if ANY of the following conditions apply [ANY] ß Non-FDA approved indications ß Hypersensitivity to Juxtapid (lomitapide) or any ingredient in the formulationa,b ß Pregnancy ß Co-administration with moderate moderate (e.g. ciprofloxacin, diltiazem, fluconazole) or strong CYP3A4 inhibitors [such as boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir,