Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.40.02 Subject: Kynamro Page: 1 of 5 Last Review Date: December 2, 2016 Kynamro Description Kynamro (mipomersen) Background Kynamro is indicated for homozygous familial hypercholesterolemia. It is an inhibitor of mrna for apolipoprotein B-100, thus preventing translation of the apolipoprotein B-100 protein. This inhibition prevents the synthesis of cholesterol, thus lowering low-density lipoprotein cholesterol (LDL-C) total cholesterol (TC), and non-high density lipoprotein-cholesterol (non-hdl-c). Kynamro is intended for use in combination with a low fat diet and other lipid-lowering treatments (1). Regulatory Status Kynamro is an oligonucleotide inhibitor of apolipoprotein B-100 synthesis indicated as an adjunct to lipid-lowering medications and diet to reduce low density lipoprotein-cholesterol (LDL- C), apolipoprotein B (apo B), total cholesterol (TC), and non-high density lipoprotein-cholesterol (non-hdl-c) in patients with homozygous familial hypercholesterolemia (HoFH) (1). The Kynamro label includes a boxed warning citing the risk of hepatotoxicity. Kynamro can cause elevations in transaminases. Kynamro also increases hepatic fat (hepatic steatosis) with or without concomitant increases in transaminases. Hepatic steatosis associated with Kynamro treatment may be a risk factor for progressive liver disease, including steatohepatitis and cirrhosis. Kynamro is contraindicated in patients with moderate or severe hepatic impairment (based on Child-Pugh category B or C), or active liver disease, including unexplained persistent elevations of serum transaminases. Before beginning treatment with Kynamro, measure alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and total
Subject: Kynamro Page: 2 of 5 bilirubin. During the first year, conduct liver-related tests monthly (ALT and AST, at a minimum). After the first year, conduct these tests at least every 3 months (1). Modify the dose of Kynamro if elevations of transaminases are observed. Discontinue treatment with Kynamro if persistent or clinically significant elevations or if transaminase elevations are accompanied by clinical symptoms of liver injury, increases in bilirubin 2x ULN, or active liver disease (1). After initiation of Kynamro therapy lipid levels should be monitored at least every 3 months for the first year. Maximal reduction of LDL-C may be seen with Kynamro therapy after approximately 6 months. Health care providers should assess the patient s LDL-C level after 6 months to determine if the LDL-C reduction achieved with Kynamro is sufficiently robust to warrant the potential risk of liver toxicity (1). The safety and effectiveness of Kynamro have not been established in patients with hypercholesterolemia who do not have HoFH. The use of Kynamro as an adjunct to LDL apheresis is not recommended. The effect of Kynamro on cardiovascular morbidity and mortality has not been determined (1). Because of the risk of hepatotoxicity, Kynamro is available only through a limited program under the REMS. Under the Kynamro REMS, only certified healthcare providers and pharmacies may prescribe and distribute Kynamro (1). Safety and effectiveness have not been established in pediatric patients (1). Related policies Juxtapid Policy This policy statement applies to clinical review performed for pre-service (Prior Approval, Precertification, Advanced Benefit Determination, etc.) and/or post-service claims. Kynamro may be considered medically necessary in patients that are 18 years of age and older with homozygous familial hypercholesterolemia; documented confirmation of diagnosis by LDL-R DNA Sequencing Test or APOB (hypercholesterolemia) Mutation Analysis; genetic confirmation of two mutant alleles at the LDLR, Apo-B, PCSK9, ARH adaptor protein 1/LDLRAP1 gene locus; recent ALT, AST, alkaline phosphatase, and total bilirubin levels and agreement to monitor levels after a dose increase or at least monthly for the first year; used in conjunction with a low fat diet; used in combination with other lipid-lowering treatments; not in
Subject: Kynamro Page: 3 of 5 combination with LDL apheresis; no moderate or severe hepatic impairment (Child-Pugh B or C) or active liver disease; physician is enrolled in the Kynamro REMS program. Kynamro is considered investigational in patients that are less than 18 years of age and for all other indications. Prior-Approval Requirements Age 18 years of age or older Diagnosis Patient must have the following: Homozygous familial hypercholesterolemia AND ALL of the following: 1. Documented confirmation of diagnosis by LDL-R DNA Sequencing Test or APOB (hypercholesterolemia) Mutation Analysis 2. Genetic confirmation of two mutant alleles at the LDLR, Apo-B, PCSK9, ARH adaptor protein 1/LDLRAP1 gene locus 3. Recent ALT, AST, alkaline phosphatase, and total bilirubin levels. a. Agreement to monitor ALT and AST levels every 3 months 4. Used in conjunction with a low fat diet 5. Used in combination with other lipid-lowering treatments 6. NOT in combination with LDL apheresis 7. NO moderate or severe hepatic impairment (Child-Pugh B or C) or active liver disease 8. Physician is enrolled in the Kynamro REMS program Prior Approval Renewal Requirements Age 18 years of age or older Diagnosis Patient must have the following:
Subject: Kynamro Page: 4 of 5 Policy Guidelines Homozygous familial hypercholesterolemia AND ALL of the following: Pre - PA Allowance None 1. Agreement to monitor ALT and AST levels every 3 months. 2. Used in conjunction with a low fat diet 3. Used in combination with other lipid-lowering treatments 4. NOT in combination with LDL apheresis 5. NO moderate or severe hepatic impairment (Child-Pugh B or C) or active liver disease 6. Physician is enrolled in the Kynamro REMS program Prior - Approval Limits Duration 12 months Prior Approval Renewal Limits Duration 12 months Rationale Summary Kynamro is an oligonucleotide inhibitor of apolipoprotein B-100 synthesis indicated as an adjunct to lipid-lowering medications and diet to reduce low density lipoprotein-cholesterol (LDL- C), apolipoprotein B (apo B), total cholesterol (TC), and non-high density lipoprotein-cholesterol (non-hdl-c) in patients with homozygous familial hypercholesterolemia (HoFH). Kynamro carries a boxed warning of hepatotoxicity which requires frequent liver function monitoring. Kynamro is contraindicated in patients with moderate or severe hepatic impairment or active liver disease. Due to the risk of hepatoxicity, Kynamro is available only through the Kynamro REMS program. The safety and efficacy of Kynamro in pediatric patients have not been established (1).
Subject: Kynamro Page: 5 of 5 Prior approval is required to ensure the safe, clinically appropriate and cost effective use of Kynamro while maintaining optimal therapeutic outcomes. References 1. Kynamro prescribing information. Cambridge MA; Genzyme Corporation. May 2016. Policy History Date April 2013 June 2013 June 2014 September 2015 April 2016 June 2016 December 2016 Action Addition to PA and reference update Addition of documented confirmation of diagnosis by LDL-R DNA Sequencing Test or APOB (hypercholesterolemia) Mutation Analysis; genetic confirmation of two mutant alleles at the LDLR, Apo-B, PCSK9, ARH adaptor protein 1/LDLRAP1 gene locus. Change of initation from 6 months to 12 months Policy number change from 5.16.02 to 5.40.02 Annual editorial review and reference update Keywords This policy was approved by the FEP Pharmacy and Medical Policy Committee on December 2, 2016 and is effective on January 1, 2017. Deborah M. Smith, MD, MPH