DOCSLIB.ORG

Kynamro, INN-Mipomersen

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Kynamro, INN-Mipomersen London, 21 March 2013 EMA/305826/2013 Committee for Medicinal Products for Human Use (CHMP) Assessment report Kynamro Solution for injection 189mg International non-proprietary name: mipomersen Procedure No. EMEA/H/C/002429/0000 Assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted. 7 Westferry Circus ● Canary Wharf ● London E14 4HB ● United Kingdom Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7523 7455 E -mail [email protected] Website www.ema.europa.eu An agency of the European Union Table of Contents 1. BACKGROUND INFORMATION ON THE PROCEDURE ..................................... 5 2. SCIENTIFIC DISCUSSION ............................................................................. 8 2.1 Introduction ............................................................................................... 8 2.2. Quality aspects ......................................................................................... 9 2.2.1. Introduction .......................................................................................... 9 2.2.2. Active Substance .................................................................................... 9 2.2.3. Finished Medicinal Product ......................................................................12 2.2.4. Discussion on chemical, pharmaceutical and biological aspects ...................15 2.2.5. Conclusions on the chemical, pharmaceutical and biological aspects ............16 2.3. Non-clinical aspects ..................................................................................16 2.3.1. Introduction .........................................................................................16 2.3.2. Pharmacology .......................................................................................17 2.3.3. Pharmacokinetics ..................................................................................19 2.3.4. Toxicology ............................................................................................21 2.3.5. Discussion on non-clinical aspects ...........................................................28 2.3.6. Conclusion on the non-clinical aspects .....................................................29 2.4. Clinical aspects ........................................................................................30 2.4.1. Introduction .........................................................................................30 2.4.2. Pharmacokinetics ..................................................................................32 2.4.3. Pharmacodynamics ................................................................................35 2.4.4. Discussion on clinical pharmacology ........................................................36 2.4.5. Conclusions on clinical pharmacology .......................................................38 2.5. Clinical efficacy ........................................................................................39 2.5.1. Dose response studies ...........................................................................40 2.5.2. Main studies .........................................................................................42 2.5.3. Discussion on clinical efficacy ..................................................................58 2.5.4. Conclusions on the clinical efficacy ..........................................................61 2.6. Clinical safety ..........................................................................................61 2.6.1. Discussion on clinical safety ....................................................................72 2.6.2. Conclusions on the clinical safety ............................................................78 2.7. Pharmacovigilance ...................................................................................79 2.8. User consultation .....................................................................................81 3. BENEFIT-RISK BALANCE ............................................................................ 82 4. RECOMMENDATIONS .................................................................................. 88 5. APPENDIX ................................................................................................ 113 Kynamro Page 2/114 List of abbreviations ACE angiotensin-converting enzyme ADR adverse drug reaction AE adverse event ALT alanine aminotransferase Amu atomic mass unit Apo A apolipoprotein A Apo B apolipoprotein B ApoB-100 Apoliloproptein B-100 ASO antisense oligonucleotide AST aspartate aminotransferase AUC area under the concentration-time curve AUC(INF) area under the concentration-time curve to infinity BID twice daily BMI body-mass index BRB bilirubin C cholesterol CDP clinical development plan CGE-UV capillary gel electrophoresis with ultraviolet detection CHD coronary heart disease CHMP Committee for Medicinal Products for Human Use CI confidence interval CL plasma clearance Cmax maximum plasma concentration CNS central nervous system CQAs Critical Quality Attributes CrCl creatinine clearance CRP C-reactive protein CSR clinical study report CT computed tomography CV(S) cardiovascular CWL Cool white fluorescent light CYP cytochrome P450 DNA deoxyribonucleic acid ELISA enzyme-linked immunosorbent assay EMA European Medicines Agency E-R exposure-response EU European Union FDA Food and Drug Administration (US) FH familial hypercholesterolaemia FLS flu like symptom FTIR Fourier transform infrared spectroscopy GC Gas chromatography GLP Good Laboratory Practices HA health authority HDL-C high density lipoprotein cholesterol HeFH heterozygous familial hypercholesterolaemia HMG-CoA hydroxyl-methyl-glutaryl-Coenzyme A HoFH homozygous familial hypercholesterolaemia HPLC High Performance Liquid Chromatography HsCRP High sensitivity C-reactive protein ICAC independent central adjudication committee ICH International Conference on Harmonisation ICH International Conference on Harmonization Kynamro Page 3/114 IDL intermediate density lipoprotein IRMPD-FT-ICR-MS infrared multi-photon decomposition-Fourier transform-ion cyclotron resonance-mass spectrometry ISR injection site reaction IV intravenous(ly) i.v. intravenous(ly) KF Karl Fischer LC-MS/MS Liquid chromatography with tandem mass spectrometry LDL low density lipoprotein LDL-C low-density lipoprotein cholesterol LDPE Low Density Polyethylene LFT liver function test Lp[a] lipoprotein A LSC Liquid scintillation counting MAA Marketing Authorisation Application MedDRA Medical Dictionary of Regulatory Activities mg milligram ml milliliter MOE 2′- methoxyethyl mRNA messenger RNA MTD maximum tolerated dose MTP microsomal triglyceride transfer protein NADPH nicotinamide adenine dinucleotide phosphate NMR Nuclear Magnetic Resonance NOAEL no-observed-adverse-effect-level OLE open-label extension PD pharmacodynamic(s) PET primary efficacy timepoint PFS Pre-filled syringes Ph. Eur.European Pharmacopoeia PK pharmacokinetic(s) PO oral(ly) Pop-PK population pharmacokinetics QD once daily QOW every other week QW once weekly QWBA quantitative whole-body autoradiography RBC red blood parameters RMP Risk Management Plan RNA ribonucleic acid ROW rest of world SA Scientific Advice SAE serious adverse event SC subcutaneous(ly) s.c. subcutaneous(ly) SCE Summary of Clinical Efficacy SOP Standard Operating Procedures SPC Summary of Product Characteristics TC total cholesterol ULN upper limit of normal US United States Vc/F apparent volume of distribution of the central compartment VLDL very low density lipoprotein WFI Water for injection Kynamro Page 4/114 1. Background information on the procedure 1.1. Submission of the dossier The applicant Genzyme Europe BV submitted on 28 July 2011 an application for Marketing Authorisation to the European Medicines Agency (EMA) for Kynamro, through the centralised procedure under Article 3(2)(a) of Regulation (EC) No 726/2004. The eligibility to the centralised procedure was agreed upon by the EMA/CHMP on 23 September 2010. The applicant applied for the following indication: Kynamro is an apolipoprotein B (apo B) synthesis inhibitor indicated as an adjunct to maximally tolerated lipid-lowering medications and diet to reduce low density lipoprotein-cholesterol (LDL-C), apo B, total cholesterol (TC), non-high density lipoprotein-cholesterol (non-HDL-C) and lipoprotein (a) [Lp(a)] in patients with homozygous familial hypercholesterolaemia (HoFH) and in patients with severe heterozygous familial hypercholesterolaemia (severe HeFH). The legal basis for this application refers to: Article 8.3 of Directive 2001/83/EC, as amended - complete and independent application. The application submitted is composed of administrative information, complete quality data, non-clinical and clinical data based on applicants’ own tests and studies and/or bibliographic literature substituting/supporting certain tests or studies. Information on Paediatric requirements Pursuant to Article 7 of Regulation (EC) No 1901/2006, the application included an EMA Decision(s) P/139/2011 on the agreement of a paediatric investigation plan (PIP). At the time of submission of the application, the PIP P/139/2011 was not yet completed as some measures were deferred. Information relating to orphan market exclusivity Similarity Pursuant to Article 8 of Regulation (EC) No. 141/2000 and Article 3 of Commission Regulation (EC) No 847/2000, the applicant did not submit a critical report addressing the possible similarity with authorised orphan medicinal products because there
Load more

Recommended publications
  • A Novel Therapeutic Drug for the Treatment of Familial Hypercholesterolemia, Hyperlipidaemia, and Hypercholesterolemia
    International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 8, Issue 3, 2016 Review Article MIPOMERSEN: A NOVEL THERAPEUTIC DRUG FOR THE TREATMENT OF FAMILIAL HYPERCHOLESTEROLEMIA, HYPERLIPIDAEMIA, AND HYPERCHOLESTEROLEMIA AJAY KUMAR1, ARUN ACHARYA2, DINOBANDHU NANDI3, NEHA SHARMA4, EKTA CHITKARA1* 1Department of Paramedical Sciences, Lovely Professional University, Phagwara-144411, Punjab (India) Email: [email protected] Received: 25 Dec 2015 Revised and Accepted: 13 Jan 2016 ABSTRACT Familial Hypercholesterolemia (FH) is one of the most common autosomal dominant disorders which exist in either heterozygous form or a homozygous form. These two forms are prevalent in 1 in 500 and 1 in a million population respectively. FH results in premature atherosclerosis; as early as childhood in case of homozygous (HoFH) form and in adults in case of heterozygous (HeFH) form. In case of HoFH both the alleles for LDL- receptor are defective, whereas the mutation in the single allele is the cause for HeFH. Both the forms of the disease are associated with high levels of LDL-C and lipoprotein (a) in plasma, with high morbidity and mortality rate caused by cardiovascular disease. In several past years, different lipid-lowering drugs like Statins (HMG-coenzyme-A reductase inhibitor), MTTP inhibitor, CETP inhibitors, PCSK9 inhibitor, thyroid mimetics, niacin, bile acid sequestrants and lipid apheresis were administered to patients with FH, to achieve the goal of reducing plasma LDL-C and lipoprotein (a). However, such drugs proved inefficient to achieve the goals because of several reasons. Mipomersen is a 20 nucleotide antisense oligonucleotide; a novel lipid-lowering therapeutic drug currently enrolled in the treatment of patients with HoFH, HeFH and other forms of hypercholesterolemia.
    [Show full text]
  • Volanesorsen Fdaadvisory Committee Meeting Briefing Document
    VOLANESORSEN FDA ADVISORY COMMITTEE MEETING BRIEFING DOCUMENT ENDOCRINE AND METABOLIC DRUGS ADVISORY COMMITTEE MEETING DATE: 10 MAY 2018 ADVISORY COMMITTEE BRIEFING MATERIALS: AVAILABLE FOR PUBLIC RELEASE Volanesorsen (ISIS 304801) Akcea Therapeutics Endocrine and Metabolic Drugs Advisory Committee Briefing Document 10 May 2018 Meeting TABLE OF CONTENTS TABLE OF CONTENTS .................................................................................................................2 TABLE OF TABLES ......................................................................................................................6 TABLE OF FIGURES .....................................................................................................................9 LIST OF ABBREVIATIONS ........................................................................................................10 1. EXECUTIVE SUMMARY ........................................................................................11 1.1 Familial Chylomicronemia Syndrome ........................................................................12 1.1.1 Overview of the Disease and Impact of Elevated Triglyceride Levels ......................12 1.1.2 Current Treatment Options .........................................................................................14 1.2 Volanesorsen Clinical Development Program ............................................................15 1.3 Efficacy and Safety of Volanesorsen ..........................................................................15
    [Show full text]
  • Ehealth DSI [Ehdsi V2.2.2-OR] Ehealth DSI – Master Value Set
    MTC eHealth DSI [eHDSI v2.2.2-OR] eHealth DSI – Master Value Set Catalogue Responsible : eHDSI Solution Provider PublishDate : Wed Nov 08 16:16:10 CET 2017 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 1 of 490 MTC Table of Contents epSOSActiveIngredient 4 epSOSAdministrativeGender 148 epSOSAdverseEventType 149 epSOSAllergenNoDrugs 150 epSOSBloodGroup 155 epSOSBloodPressure 156 epSOSCodeNoMedication 157 epSOSCodeProb 158 epSOSConfidentiality 159 epSOSCountry 160 epSOSDisplayLabel 167 epSOSDocumentCode 170 epSOSDoseForm 171 epSOSHealthcareProfessionalRoles 184 epSOSIllnessesandDisorders 186 epSOSLanguage 448 epSOSMedicalDevices 458 epSOSNullFavor 461 epSOSPackage 462 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 2 of 490 MTC epSOSPersonalRelationship 464 epSOSPregnancyInformation 466 epSOSProcedures 467 epSOSReactionAllergy 470 epSOSResolutionOutcome 472 epSOSRoleClass 473 epSOSRouteofAdministration 474 epSOSSections 477 epSOSSeverity 478 epSOSSocialHistory 479 epSOSStatusCode 480 epSOSSubstitutionCode 481 epSOSTelecomAddress 482 epSOSTimingEvent 483 epSOSUnits 484 epSOSUnknownInformation 487 epSOSVaccine 488 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 3 of 490 MTC epSOSActiveIngredient epSOSActiveIngredient Value Set ID 1.3.6.1.4.1.12559.11.10.1.3.1.42.24 TRANSLATIONS Code System ID Code System Version Concept Code Description (FSN) 2.16.840.1.113883.6.73 2017-01 A ALIMENTARY TRACT AND METABOLISM 2.16.840.1.113883.6.73 2017-01
    [Show full text]
  • Annexes of the Annual Report 2011
    1 June 2012 EMA/363033/2012 Office of the Executive Director Annexes of the annual report 2011 The main body of this report is available on the website of the European Medicines Agency (EMA) here. 7 Westferry Circus ● Canary Wharf ● London E14 4HB ● United Kingdom Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7418 8416 E-mail [email protected] Website www.ema.europa.eu An agency of the European Union © European Medicines Agency, 2012. Reproduction is authorised provided the source is acknowledged. Table of contents Annex 1 – Members of the Management Board ................................................... 3 Annex 2 – Members of the Committee for Medicinal Products for Human Use ......... 5 Annex 3 – Members of the Committee for Medicinal Products for Veterinary Use .... 9 Annex 4 – Members of the Committee for Orphan Medicinal Products.................. 11 Annex 5 – Members of the Committee on Herbal Medicinal Products ................... 13 Annex 6 – Members of the Paediatric Committee .............................................. 16 Annex 7 – Members of the Committee for Advanced Therapies ........................... 18 Annex 8 – National competent authority partners ............................................. 20 Annex 9 – Budget summaries 2010–2011........................................................ 31 Annex 10 – Establishment plan ...................................................................... 32 Annex 11 – CHMP opinions in 2011 on medicinal products for human use ............ 33 Annex 12 – CVMP opinions in 2011
    [Show full text]
  • Mipomersen (KYNAMRO®) Monograph
    Mipomersen (KYNAMRO®) Monograph Mipomersen (KYNAMRO®) National Drug Monograph May 2015 VA Pharmacy Benefits Management Services, Medical Advisory Panel, and VISN Pharmacist Executives The purpose of VA PBM Services drug monographs is to provide a focused drug review for making formulary decisions. Updates will be made when new clinical data warrant additional formulary discussion. Documents will be placed in the Archive section when the information is deemed to be no longer current. FDA Approval Information1 Description/Mechanism of Mipomersen (KYNAMRO) is the first-in-class antisense oligonucleotide Action (ASO) inhibitor directed at inhibiting the production of human apolipoprotein B-100 (ApoB). Apoliprotein B is the major structural lipoprotein of very low- density lipoprotein cholesterol (VLDL-C). Reduced availability of ApoB results in reduced production of VLDL in the liver and therefore less VLDL is released into the circulation. Reduced VLDL results in lower levels of low-density lipoprotein cholesterol (LDL-C) and other lipoproteins. Additionally, VLDL transports triglycerides (TGs) from the liver into the circulation. Therefore, lower levels of VLDL results in accumulation of TGs in the liver. Indication(s) Under Review in Mipomersen is approved as an adjunct to lipid-lowering medications and diet to this document (may include reduce LDL-C, ApoB, total cholesterol (TC) and non-high density lipoprotein off label) cholesterol (HDL-C) in patients with homozygous familial hypercholesterolemia (HoFH). The safety and effectiveness of mipomersen has not been established in patients with hypercholesterolemia who do not have HoFH. The safety and effectiveness of mipomersen as an adjunct to LDL apheresis is unknown; and therefore the treatment combination is not recommended.
    [Show full text]
  • Mipomersen Sodium Manufacturer1: Genzyme Corp. Drug Class1,2
    Brand Name: Kynamro ® Generic Name: Mipomersen Sodium Manufacturer1: Genzyme Corp. Drug Class1,2: Apo B Synthesis Inhibitor1,2 Uses: Labeled Uses1,2,3,4,: Homozygous familial hypercholesterolemia Unlabeled Uses4: Coronary arteriosclerosis; heterozygous familial hypercholesterolemia Mechanism of Action:1,2,3,4, Mipomersen sodium is an oligonucleotide inhibitor of apo B-100 synthesis, inhibiting synthesis of apo B by sequence-specific binding to its messenger ribonucleic acid (mRNA) through enzyme-mediated pathways or disruption of mRNA function through binding alone. Its binding to apo B mRNA as a complement in the coding region of the apo B-100 mRNA allows hybridization of mipomersen to the cognate mRNA and RNase H- mediated degradation of the cognate mRNA with inhibition of translation of the apo B-100 protein resulting in decreased LDL and VLDL levels Pharmacokinetics1,2,3,4: Absorption: Tmax 3-4 hours Vd Not reported t ½ 1-2 months Clearance Not reported Protein binding >90% Bioavailability 54-78% Metabolism: Mipomersen is metabolized in tissues by endonucleases to form shorter oligonucleotides that are then substrates for additional metabolism by exonucleases. Mipomersen is not a substrate for cytochrome P450 metabolism. Elimination: The elimination of mipomersen involves metabolism in tissues and excretion primarily in the urine. Both mipomersen and putative shorter oligonucleotide metabolites were identified in human urine. Urinary recovery was limited in humans with less than 4% within the 24 hours postdose. Efficacy: McGowan MP, Tardif JC, Ceska R, Burgess LJ, Soran H, Gouni-Berthold I, Wagener G, Chasan-Taber S. Randomized, placebo-controlled trial of mipomersen in patients with severe hypercholesterolemia receiving maximally tolerated lipid-lowering therapy.
    [Show full text]
  • Treatment Strategy for Dyslipidemia in Cardiovascular Disease Prevention: Focus on Old and New Drugs
    pharmacy Article Treatment Strategy for Dyslipidemia in Cardiovascular Disease Prevention: Focus on Old and New Drugs Donatella Zodda 1,*, Rosario Giammona 2 and Silvia Schifilliti 2 1 Drug Department of Local Health Unit (ASP), Viale Giostra, 98168 Messina, Italy 2 Clinical Pharmacy Fellowship, University of Messina, Viale Annunziata, 98168 Messina, Italy; [email protected] (R.G.); silvia.schifi[email protected] (S.S.) * Correspondence: [email protected]; Tel.: +39-090-3653902 Received: 12 November 2017; Accepted: 11 January 2018; Published: 21 January 2018 Abstract: Prevention and treatment of dyslipidemia should be considered as an integral part of individual cardiovascular prevention interventions, which should be addressed primarily to those at higher risk who benefit most. To date, statins remain the first-choice therapy, as they have been shown to reduce the risk of major vascular events by lowering low-density lipoprotein cholesterol (LDL-C). However, due to adherence to statin therapy or statin resistance, many patients do not reach LDL-C target levels. Ezetimibe, fibrates, and nicotinic acid represent the second-choice drugs to be used in combination with statins if lipid targets cannot be reached. In addition, anti-PCSK9 drugs (evolocumab and alirocumab) provide an effective solution for patients with familial hypercholesterolemia (FH) and statin intolerance at very high cardiovascular risk. Recently, studies demonstrated the effects of two novel lipid-lowering agents (lomitapide and mipomersen) for the management of homozygous FH by decreasing LDL-C values and reducing cardiovascular events. However, the costs for these new therapies made the cost–effectiveness debate more complicated. Keywords: lipid lowering therapy; dyslipidemia; statins; fibrate; PCSK9 inhibitors; lomitapide 1.
    [Show full text]
  • 203568Orig1s000
    CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 203568Orig1s000 MEDICAL REVIEW(S) CLINICAL REVIEW Application Type NDA-Type 1 NME 505 (b)(1) Application Number(s) 203568 Priority or Standard Standard Submit Date(s) 29 March 2012 Received Date(s) 29 March 2012 PDUFA Goal Date 29 January 2013 Division / Office DMEP/ ODE II/ OND Reviewer Name(s) Eileen M. Craig, MD Review Completion Date 06 November 2012 Established Name Mipomersen sodium (Proposed) Trade Name Kynamro Therapeutic Class Lipid lowering; antisense inhibitor Applicant Genzyme Corp. Formulation(s) Injection Dosing Regimen 200 mg SQ weekly Indication(s) to reduce LDL-C, apo B, TC, non-HDL-C and lipoprotein (a) Intended Population(s) Homozygous familial hypercholesterolemia Template Version: March 6, 2009 Reference ID: 3221077 Clinical Review Eileen M. Craig, MD NDA 203568 Kynamro (mipomersen sodium) Table of Contents 1 RECOMMENDATIONS/RISK BENEFIT ASSESSMENT ....................................... 10 1.1 Recommendation on Regulatory Action ........................................................... 10 1.2 Risk Benefit Assessment.................................................................................. 10 1.2.1 Efficacy ......................................................................................................... 10 1.2.2. Safety........................................................................................................... 14 1.3 Recommendations for Postmarket Risk Evaluation and Mitigation Strategies . 20 1.4 Recommendations for Postmarket
    [Show full text]
  • Ibm Micromedex® Carenotes Titles by Category
    IBM MICROMEDEX® CARENOTES TITLES BY CATEGORY DECEMBER 2019 © Copyright IBM Corporation 2019 All company and product names mentioned are used for identification purposes only and may be trademarks of their respective owners. Table of Contents IBM Micromedex® CareNotes Titles by Category Allergy and Immunology ..................................................................................................................2 Ambulatory.......................................................................................................................................3 Bioterrorism ...................................................................................................................................18 Cardiology......................................................................................................................................18 Critical Care ...................................................................................................................................20 Dental Health .................................................................................................................................22 Dermatology ..................................................................................................................................23 Dietetics .........................................................................................................................................24 Endocrinology & Metabolic Disease ..............................................................................................26
    [Show full text]
  • Kynamro Mipomersen MCP156
    Subject: Kynamro (mipomersen) Original Effective Date: 10/30/2013 Policy Number: MCP-156 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. SUMMARY OF EVIDENCE/POSITION This policy addresses the use of Kynamro (mipomersen) for the treatment of homozygous familial hypercholesterolemia (HoFH).
    [Show full text]
  • INTEGRATED REVIEW Executive Summary Interdisciplinary Assessment Appendices NDA211617 Nexlizet I Bempedoic Acid and Ezetimibe
    CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 211617Orig1s000 INTEGRATED REVIEW Executive Summary Interdisciplinary Assessment Appendices NDA211617 Nexlizet I bempedoic acid and ezetimibe Integrated Review Table 1. Administrative Application Information Category Application Information Application type NDA Application number 211617 Priority or standard Standard Submit date 2/26/2019 Received date 2/26/2019 PDUFA goal date 2/26/2020 Division/office Division of Metabolism and Endoc1inology Products (DMEP) Review completion date 2/25/2020 Established name Bempedoic acid and ezetimibe (Proposed) trade name Nexlizet Phannacologic class an adenosine triphosphate-citrate lyase (ACL) inhibitor and a cholesterol abso1ption inhibitor Code name ETC-I 002/ezetimibe Applicant Esperion Therapeutics, Inc. Dose form/formulation Tablets, 180 mg/10 mg One tablet dail Applicant proposed Adjunct to diet indication(s)/population(s) Proposed SNOMED 55822004 (hyperlipidemia) indication Regulatory action Approval Approved adjunct to diet and maximally tolerated stat.in therapy for the indication(s)/population(s) treatment of adults with heterozygous familial (if applicable) hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL-C Approved SNOMED 55822004 (hyperlipidemia) indication Integrated Review Template, version date 2019/06/14 Reference ID 4566970 1'$ 1H[OL]HW EHPSHGRLF DFLG DQG H]HWLPLEH 7DEOH RI &RQWHQWV 7DEOH RI 7DEOHV Y 7DEOH RI )LJXUHV YLLL *ORVVDU\ , ([HFXWLYH 6XPPDU\ 6XPPDU\
    [Show full text]
  • Management of Lipids Beyond Statin Therapy
    9/23/2015 Management of Lipids Disclosures/Conflict of Interest Beyond Statin Therapy • Neither speaker has a conflict of interest in relation to this presentation Jessica L. Kerr, PharmD, CDE Associate Professor SIUE School of Pharmacy Jared Sheley, PharmD, BCPS Clinical Assistant Professor SIUE School of Pharmacy Pre‐test Question #1 Objectives Which of the following is the cause for elevated cholesterol • Describe the pathophysiology of lipid disorders and the populations at risk for levels in patients with familial hypercholesterolemia? cardiovascular disease • Compare and contrast currently available lipid management guidelines A. Being raised with poor dietary choices that cause increased consumption • Discuss the efficacy and safety for FDA approved non‐statin therapy and their of high cholesterol foods as an adult role in current medical management for lipid disorders B. Increased biosynthesis of cholesterol • Evaluate and apply evidence based literature for novel drug classes new to C. Decreased metabolism of LDL lipid management D. Decreased production of HDL Pre‐test Question #2 Meet Lydia Pre‐test Case #1 Which of the following medications has long term efficacy • 62 yo female s/p MI and T2DM, HTN and hyperlipidemia/‐triglyceridemia. data showing reduction in cardiovascular events? • Meds: ASA 81mg daily, Atorvastatin 10mg daily, Lisinopril 40mg daily, Metformin 1000mg twice daily, Metoprolol Succinate 100mg daily (choose all that apply) • Labs: Chem 7 –wnl; LFT –wnl; A1c 7.5% Today : TC: 215, TG: 1,401, HDL:42, dLDL: 86 (mg/dl) A. Ezetimibe –Results of Atorvastatin 10mg daily being added T‐3 mo: TC: 215, TG: 1,589, HDL: 40, dLDL: 126 (mg/dl) B.
    [Show full text]