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    Heart 2013 Heart 2013 Document Transcript

    • 2013REPORTBiopharmaceutical research companiesare developing 215 medicines for two ofthe leading causes of death in Ameri-cans—heart disease and stroke. Medi-cines have helped cut deaths from thesediseases by 30 percent between 2001and 2011, and in 2008 stroke dropped tothe fourth leading cause of death afterbeing the third for more than 50 years.This progress is in large part due toinnovative medicines.Despite this progress, heart disease andstroke persist as key public health chal-lenges. According to the American HeartAssociation, every 39 seconds an Ameri-can dies from cardiovascular disease, andmore than 83 million Americans haveat least one type of the disease. Thesediseases cost our society more than $312billion a year.The medicines in development include:30 for heart failure, 29 for lipid disorders(such as high cholesterol), 19 for stroke,and 17 each for high blood pressure andischemic disorders. Many of the potentialmedicines use cutting-edge technologiesand new scientific approaches, such as:• A gene therapy that uses a patient’sown cells to treat heart failure.• A medicine that blocks the transfer ofgood (HDL) cholesterol to bad (LDL).• A genetically-engineered medicine thatdissolves clots to treat stroke.All of the medicines are either in clinicaltrials or awaiting review by the Food andDrug Administration. A glossary of termsbegins on page 24. Links to sponsorcompany websites provide more informa-tion on the potential products.For information on the current innovativeproducts in the pipeline for cardiovasculardisease and the value of medicines forpatients and our healthcare system, pleasesee Medicines in Development for HeartDisease and Stroke 2013—Overview.Biopharmaceutical Research Companies AreDeveloping More Than 200 Medicines forCardiovascular DiseaseMedicines in DevelopmentHeart Disease and StrokeA Report on Cardiovascular Diseasepresented by america’s biopharmaceutical research companiesLipidDisordersHypertension3017 17IschemicDisorders29HeartFailureStroke19ApplicationSubmittedPhase IIIPhase IIPhase IMedicines in DevelopmentFor Heart Disease and Stroke83.6 MillionAmericans SufferFrom CardiovascularDiseaseMore Than700,000Die Each Year
    • Medicines in Development Heart Disease and Stroke 20132Medicines in Development for Heart Disease and Stroke*For more information about a specific medicine or company in the report, please click on the provided link.Acute Coronary SyndromeProduct Name Sponsor Indication Development Phase*cangrelor The Medicines CompanyParsippany, NJacute coronary syndrome(see also coronary artery disease,thrombosis)Phase Iwww.themedicinescompany.comCER-001(recombinant HDL)CerenisTherapeuticsAnn Arbor, MIacute coronary syndrome(see also lipid disorders)Phase IIwww.cerenis.comgevokizumab ServierParis, FranceXOMABerkeley, CAacute coronary syndrome Phase IIwww.servier.comwww.xoma.cominclacumab(RG1512)RocheNutley, NJacute coronary syndrome(see also heart attack, peripheralvascular disease)Phase IIwww.roche.comlosmapimod(p38 kinase inhibitor)GlaxoSmithKlineRsch. Triangle Park, NCacute coronary syndrome Phase IIwww.gsk.comPF-06282999 PfizerNew York, NYacute coronary syndrome Phase Iwww.pfizer.comREG1(anivamersen-pegnivacoginintravenous)Regado BiosciencesBasking Ridge, NJacute coronary syndrome Phase IIwww.regadobio.comRVX-208(BET protein inhibitor)ResverlogixCalgary, Canadaacute coronary syndrome(see also atherosclerosis)Phase IIwww.resverlogix.comvorapaxar(thrombin/PAR-1 receptorantagonist)MerckWhitehouse Station, NJacute coronary syndrome(prevention) (FastTrack)(see also thrombosis)Phase IIIwww.merck.comVT-111a VironTherapeuticsOntario, Canadaacute coronary syndrome Phase IIwww.vironinc.comVytorin®ezetimibe/simvastatinfixed-dose combinationMerckWhitehouse Station, NJacute coronary syndrome Phase IIIwww.merck.comXarelto®rivaroxabanBayer HealthCare PharmaceuticalsWayne, NJJanssen Research & DevelopmentRaritan, NJacute coronary syndrome(FastTrack)(see also thrombosis, other)application submittedwww.bayerpharma.comwww.janssenrnd.com
    • Medicines in Development Heart Disease and Stroke 2013 3Medicines in Development for Heart Disease and StrokeAdjunctive Therapies, RevascularizationProduct Name Sponsor Indication Development PhaseATryn®antithrombin(recombinant)(Orphan Drug)rEVO BiologicsFramingham, MAheparin resistance in patientsundergoing coronary artery bypassgraft (CABG) surgery(see also hypertension)--------------------------------------heparin resistance in patientsundergoing CABG surgery inneonatesPhase IIIwww.gtc-bio.com-----------------------------------------Phase Iwww.gtc-bio.comCMX-2043(proto-oncogene protein CAKT modulator)IschemixMaynard, MAprevention of ischemia-reperfusioninjury in patients undergoingpercutaneous coronaryintervention (PCI)Phase IIwww.ischemix.commyolimus-eluting stent Elixir MedicalSunnyvale, CAcoronary artery restenosis(prevention)Phase Iwww.elixirmedical.comnovolimus-eluting coronary stent Elixir MedicalSunnyvale, CAcoronary artery restenosis(prevention)in clinical trialswww.elixirmedical.comPRT-201 ProteonTherapeuticsWaltham, MAvascular access for hemodialysis(see also peripheral vasculardisease)Phase IIwww.proteontherapeutics.comranolazine Gilead SciencesFoster City, CAincomplete revascularizationin patients who undergo PCIPhase IIIwww.gilead.comsirolimus-eluting coronary stent REVA MedicalSan Diego, CAcoronary artery restenosis in clinical trialswww.teamreva.comsirolimus-eluting coronary stent Svelte Medical SystemsNew Providence, NJischemic heart disorder Phase I/IIwww.sveltemedical.comSRM003(endothelial cell therapy)Shire PharmaceuticalsWayne, PAprevention of peripheral vascularcomplications in patientsundergoing arteriovenous accessprocedures for hemodialysisPhase IIwww.shire.com
    • Medicines in Development Heart Disease and Stroke 20134Medicines in Development for Heart Disease and StrokeArrhythmia, Atrial FibrillationProduct Name Sponsor Indication Development PhaseARM036 ARMGO PharmaTarrytown, NYcatecholaminergic polymorphicventricular tachycardia type 1(see also heart failure)Phase IIwww.armgo.comazimilide Forest LaboratoriesNew York, NYventricular arrhythmia Phase IIIwww.frx.comBMS-919373(Ikur antagonist)Bristol-Myers SquibbPrinceton, NJatrial fibrillation Phase Iwww.bms.comdanegaptide(ZP1609)Zealand PharmaCopenhagen, Denmarkatrial fibrillation Phase Iwww.zealandpharma.comGS-6615(sodium channel antagonist)Gilead SciencesFoster City, CAarrhythmia(see also ischemic disorders)Phase Iwww.gilead.comISIS-CRPRx(C-reactive protein inhibitor)Isis PharmaceuticalsCarlsbad, CAparoxysmal atrial fibrillation Phase Iwww.isispharm.comOPC-108459 Otsuka America PharmaceuticalRockville, MDparoxysmal and persistent atrialfibrillationPhase Iwww.otsuka.comranolazine/dronedaronefixed-dose combinationGilead SciencesFoster City, CAparoxysmal atrial fibrillation Phase IIwww.gilead.comvanoxerine ChanRxCleveland, OHatrial fibrillation Phase IIwww.chanrx.comvernakalant(oral)Cardiome PharmaVancouver, Canadaatrial fibrillation Phase IIwww.cardiome.comAtherosclerosisProduct Name Sponsor Indication Development PhaseACP-501(rhLCAT)AlphaCore PharmaAnn Arbor, MIatherosclerosis(see also coronary artery disease)Phase Iwww.alphacorepharma.comACZ885(canakinumab)Novartis PharmaceuticalsEast Hanover, NJatherosclerosis in patients withtype 2 diabetes(see also other)Phase IIwww.novartis.comanacetrapib(MK-0859)MerckWhitehouse Station, NJatherosclerosis(see also lipid disorders)Phase IIIwww.merck.comBMS-852927(LXR modulator)Bristol-Myers SquibbPrinceton, NJatherosclerosis Phase Iwww.bms.com
    • Medicines in Development Heart Disease and Stroke 2013 5Medicines in Development for Heart Disease and StrokeAtherosclerosisProduct Name Sponsor Indication Development PhaseBMS-962476(PCSK9 adnectin)Bristol-Myers SquibbPrinceton, NJatherosclerosis Phase Iwww.bms.comCSL-112(cholesterol modulator)CSLVictoria, Australiaatherosclerosis Phase IIwww.csl.com.audarapladib(Lp-PLA2 inhibitor)GlaxoSmithKlineRsch. Triangle Park, NCatherosclerosis Phase IIIwww.gsk.comISIS-APOARx(antisense RNA inhibitor)Isis PharmaceuticalsCarlsbad, CAatherosclerosis Phase Iwww.isispharm.comrilapladib GlaxoSmithKlineRsch. Triangle Park, NCatherosclerosis Phase II completedwww.gsk.comRVX-208(BET protein inhibitor)ResverlogixCalgary, Canadaatherosclerosis(see also acute coronary syndrome)Phase IIwww.resverlogix.comTekturna®aliskirenNovartis PharmaceuticalsEast Hanover, NJatherosclerosis in coronaryartery disease(see also heart failure,hypertension)Phase IIIwww.novartis.comVB201(IL-12 subunit p40 inhibitor)VBLTherapeuticsOr Yehuda, Israelatherosclerosis Phase IIwww.vblrx.comCoronary Artery DiseaseProduct Name Sponsor Indication Development PhaseACP-501(rhLCAT)AlphaCore PharmaAnn Arbor, MIcoronary artery disease(see also atherosclerosis)Phase Iwww.alphacorepharma.comcangrelor The Medicines CompanyParsippany, NJcoronary artery disease in patientsrequiring percutaneous coronaryintervention (PCI)(see also acute coronary syndrome,thrombosis)Phase IIIwww.themedicinescompany.comcardiovascular therapyreleasing balloon(drug-coated Angiosculpt®)AngioScoreFremont, CAcoronary artery restenosis Phase IIwww.angioscore.comcoronary artery diseasegene therapyBioCardiaSan Carlos, CAcoronary artery disease Phase IIwww.biocardia.com
    • Medicines in Development Heart Disease and Stroke 20136Medicines in Development for Heart Disease and StrokeCoronary Artery DiseaseProduct Name Sponsor Indication Development Phasefibroblast growth factor-1 (FGF-1) CardioVascular BioTherapeuticsLas Vegas, NVsevere coronary heart disease Phase IIwww.cvbt.comLT-1951(oligo-L-arginine)LumenTherapeuticsMenlo Park, CAcoronary artery restenosis Phase I/IIwww.lumentherapeutics.compradigastat(LCQ908)Novartis PharmaceuticalsEast Hanover, NJcoronary artery disease(see also lipid disorders)Phase IIwww.novartis.comRG7652(PCSK9 protein inhibitor)GenentechSouth San Francisco, CAcoronary heart disease Phase IIwww.gene.comHeart Attack (Myocardial Infarction)Product Name Sponsor Indication Development Phaseabciximab(intracoronary infusion)Atrium Medical CorporationHudson, NHmyocardial infarction(new delivery system)Phase IIIwww.atriummed.comadipose-derived regenerative cell(ADRC) therapyCytoriTherapeuticsSan Diego, CAacute myocardial infarction(see also ischemic disorders)Phase IIwww.cytori.comAMR-001(stem cell therapy)Amorcyte (NeoStem)New York, NYmyocardial infarction Phase Iwww.neostem.comBB3(HGF mimetic)Angion BiomedicaUniondale, NYacute myocardial infarction Phase IIwww.angion.comBrilinta®ticagrelorAstraZenecaWilmington, DEprior myocardial infarction(see also peripheral vasculardisease)Phase IIIwww.astrazeneca.comCAP-1002(allogeneic cardiosphere-derivedstem cell therapy)CapricorBeverly Hills, CAmyocardial infarction Phase I/IIwww.capricor.cominclacumab RocheNutley, NJmyocardial infarction(see also acute coronary syndrome,peripheral vascular disease)Phase IIwww.roche.comischemic tolerant allogeneicmesenchymal stem cell therapyStemedica CellTechnologiesSan Diego, CAacute myocardial infarction Phase IIwww.stemedica.commesenchymal stem cell therapy MesoblastNew York, NYheart attack(see also heart failure)Phase IIwww.mesoblast.com
    • Medicines in Development Heart Disease and Stroke 2013 7Medicines in Development for Heart Disease and StrokeHeart Attack (Myocardial Infarction)Product Name Sponsor Indication Development PhaseMultiStem®stem cell therapyAthersysCleveland, OHacute myocardial infarction(see also stroke)Phase I completedwww.athersys.comNEU 2000 GNT PharmaYongin, South Koreamyocardial infarction(see also stroke)Phase I completedwww.gntpharma.comProchymal®remestemcel-LOsirisTherapeuticsColumbia, MDacute myocardial infarction Phase IIwww.osiris.comHeart Failure (Congestive Heart Failure)Product Name Sponsor Indication Development Phasealbiglutide(GSK716155)GlaxoSmithKlineRsch. Triangle Park, NCheart failure Phase II completedwww.gsk.comANX-042(natriuretic-peptide)AnexonCambridge, MAacute decompensated heart failure Phase Iwww.anexonrx.comARM036 ARMGO PharmaTarrytown, NYchronic heart failure(see also arrhythmia)Phase IIwww.armgo.comBAY 868050(vasopressin receptor antagonist)Bayer HealthCare PharmaceuticalsWayne, NJheart failure Phase Iwww.bayerpharma.comBAY 948862(mineralocorticoid receptor [MR]antagonist)Bayer HealthCare PharmaceuticalsWayne, NJchronic heart failure Phase IIwww.bayerpharma.comBAY 1021189(guanylate cyclase stimulant)Bayer HealthCare PharmaceuticalsWayne, NJheart failure Phase Iwww.bayerpharma.comBAY 1067197(partial adenosine A1 agonist)Bayer HealthCare PharmaceuticalsWayne, NJheart failure Phase Iwww.bayerpharma.comBMS-986046(PEG-relaxin)AmbrxLa Jolla, CABristol-Myers SquibbPrinceton, NJheart failure Phase Iwww.ambrx.comwww.bms.combucindolol companion diagnostic ARCA biopharmaBroomfield, COLabCorpBurlington, NCheart failure (diagnosis) in clinical trialswww.arcabiopharma.comwww.labcorp.com
    • Medicines in Development Heart Disease and Stroke 20138Medicines in Development for Heart Disease and Strokecenderitide NileTherapeuticsSan Mateo, CAacute heart failure(FastTrack)--------------------------------------chronic heart failure(FastTrack)Phase IIwww.nilethera.com-----------------------------------------Phase Iwww.nilethera.comCLP-1001(sodium-potassium-chloridesymporter inhibitor)SorbentTherapeuticsSunnyvale, CAcongestive heart failure in patientswith chronic kidney diseasePhase IIwww.sorbent.comCXL-1020(nitroxyl donor)Cardioxyl PharmaceuticalsChapel Hill, NCacute decompensated heart failure Phase IIwww.cardioxyl.comGencaro™bucindololARCA biopharmaBroomfield, COgenotype-defined heart failure(FastTrack)application submittedwww.arcabiopharma.comGGF2(recombinant neuregulin-1)AcordaTherapeuticsArdsley, NYheart failure(FastTrack)Phase Iwww.acorda.comGSK2849466(selective androgen receptormodulator)GlaxoSmithKlineRsch. Triangle Park, NCheart failure Phase Iwww.gsk.comJNJ-39588146 Janssen Research & DevelopmentRaritan, NJheart failure Phase IIwww.janssenrnd.comJVS-100(stromal cell-derived factor-1)JuventasTherapeuticsCleveland, OHheart failure(see also ischemic disorders)Phase IIwww.juventasinc.comLCZ696(ARB/NEP inhibitor)Novartis PharmaceuticalsEast Hanover, NJheart failure(see also hypertension)Phase IIIwww.novartis.commesenchymal stem cell therapy MesoblastNew York, NYcongestive heart failure(see also heart attack)Phase IIwww.mesoblast.comMydicar®SERCA 2a gene therapyCelladonSan Diego, CAadvanced (Class III/IV) heart failure(FastTrack)--------------------------------------chronic heart failurePhase IIwww.celladon.net-----------------------------------------Phase II completedwww.celladon.netMyoCell®stem cell therapyBioheartSunrise, FLheart failure Phase II/IIIwww.bioheartinc.comMyoCell® SDF1muscle stem cell therapy(second-generation)BioHeartSunrise, FLcongestive heart post myocardialinfarctionPhase Iwww.bioheartinc.comHeart Failure (Congestive Heart Failure)Product Name Sponsor Indication Development Phase
    • Medicines in Development Heart Disease and Stroke 2013 9Medicines in Development for Heart Disease and Strokeomecamtiv mecarbil AmgenThousand Oaks, CACytokineticsSouth San Francisco, CAheart failure Phase IIwww.amgen.comwww.cytokinetics.comPL-3994(natriuretic-peptide)PalatinTechnologiesCranbury, NJcongestive heart failure(see also hypertension)Phase IIwww.palatin.comrecombinant humanneuregulin-1 betaZensunShanghai, Chinastable chronic heart failure Phase IIwww.zensun.comserelaxin(RLX030)Novartis PharmaceuticalsEast Hanover, NJacute heart failure(FastTrack)--------------------------------------chronic heart failurePhase IIIwww.novartis.com-----------------------------------------Phase IIwww.novartis.comTekturna®aliskirenNovartis PharmaceuticalsEast Hanover, NJacute decompensated heart failure(see also atherosclerosis,hypertension)--------------------------------------reduction of cardiovascular death/hospitalization in chronic heartfailure patientsPhase III completedwww.novartis.com-----------------------------------------Phase IIIwww.novartis.comTRV027(angiotensin type 1 receptorantagonist)Forest LaboratoriesNew York, NYTrevenaKing of Prussia, PAacute heart failure(late-stage disease)Phase IIwww.frx.comwww.trevenainc.comularitide CardiorentisZug, Switzerlandacute heart failure Phase IIIwww.cardiorentis.churocortin 2 Neurocrine BiosciencesSan Diego, CAcongestive heart failure Phase IIwww.neurocrine.comHypertension (High Blood Pressure)Product Name Sponsor Indication Development PhaseAHU377(neprilysin inhibitor)Novartis PharmaceuticalsEast Hanover, NJessential hypertension Phase IIwww.novartis.comATryn®antithrombin(recombinant)rEVO BiologicsFramingham, MApreeclampsia(see also adjunctive therapies)Phase IIwww.gtc-bio.comHeart Failure (Congestive Heart Failure)Product Name Sponsor Indication Development Phase
    • Medicines in Development Heart Disease and Stroke 201310Medicines in Development for Heart Disease and Strokecandesartan cilexetil/nifedipinefixed-dose combinationBayer HealthCare PharmaceuticalsWayne, NJessential hypertension Phase IIIwww.bayerpharma.comdigoxin immune Fab (DIF)(Orphan Drug)Glenveigh PharmaceuticalsChattanooga, TNpreeclampsia(FastTrack)Phase IIwww.glenveigh.comEdarbi®azilsartan medoxomilTakeda PharmaceuticalsDeerfield, ILhypertension (pediatric) Phase Iwww.takeda.comGSK2944406(amlodipine/losartanfixed-dose combination)GlaxoSmithKlineRsch. Triangle Park, NChypertension Phase Iwww.gsk.comHL-040XC(atorvastatin/losartanfixed-dose combination)HanAll BiopharmaSeoul, South Koreahypertension(see also lipid disorders)Phase IIwww.hanall.co.krHT-101(amiloride/spironolactone)HemodynamicTherapeuticsDurham, NCobesity-related resistanthypertensionPhase IIwww.hemodynamictx.comKD027(PDE5 inhibitor)Kadmon PharmaceuticalsWarrendale, PAhypertension Phase Iwww.kadmon.comLCZ696(ARB/NEP inhibitor)Novartis PharmaceuticalsEast Hanover, NJessential hypertension(see also heart failure)Phase IIwww.novartis.comMK-7145 MerckWhitehouse Station, NJhypertension Phase I completedwww.merck.comMK-8150 MerckWhitehouse Station, NJhypertension Phase Iwww.merck.comnebivolol/valsartanfixed-dose combinationForest LaboratoriesNew York, NYessential hypertension Phase IIIwww.frx.comPB1046(Vasomera)PhaseBio PharmaceuticalsMalvern, PAessential hypertension Phase I/IIwww.phasebio.comperindopril/amlodipinefixed-dose combinationXOMABerkeley, CAhypertension Phase IIIwww.xoma.comPL-3994(natriuretic-peptide)PalatinTechnologiesCranbury, NJhypertension(see also heart failure)Phase IIwww.palatin.comTekturna®aliskirenNovartis PharmaceuticalsEast Hanover, NJhypertension in children age6-17 years of age(see also atherosclerosis, heartfailure)Phase IIIwww.novartis.comHypertension (High Blood Pressure)Product Name Sponsor Indication Development Phase
    • Medicines in Development Heart Disease and Stroke 2013 11Medicines in Development for Heart Disease and Stroke99m-Tc-EC-G CellPointCentennial, COmyocardial ischemia (diagnosis) Phase IIwww.cellpointweb.comAmiscan™Tc-99m-glucarateMolecularTargetingTechnologiesWest Chester, PAacute coronary syndrome(diagnosis)Phase IIwww.mtarget.comBFPET™(myocardial perfusion imagingagent)FluoroPharmaMontclair, NJcoronary artery disease (diagnosis) Phase Iwww.fluoropharma.comCardioPET™cardiac PET imaging agentFluoroPharmaMontclair, NJcoronary artery disease (diagnosis) Phase IIwww.fluoropharma.comfluorine-18-ML-10 IBA Molecular USDulles, VAstroke (diagnosis) Phase IIwww.iba-molecular.comflurpiridaz F-18 Lantheus Medical ImagingN. Billerica, MAcoronary artery disease (diagnosis) Phase IIIwww.lantheus.comImagify™perflubutaneAcusphereLexington, MAcoronary artery disease (diagnosis) Phase IIIwww.acusphere.comLMI 1195(PET imaging agent)Lantheus Medical ImagingN. Billerica, MAheart failure (diagnosis) Phase Iwww.lantheus.comThromboView®Tc-99m 3B6/22 anti-fibrin mAbAGEN Biomedical(Agenix)Victoria, Australiadeep vein thrombosis (diagnosis),pulmonary thrombosis (diagnosis)Phase IIwww.agenix.comIschemic DisordersProduct Name Sponsor Indication Development PhaseACY001(autologous AC133+ selected adultbone marrow-derived stem celltherapy)Compass BiomedicalCleveland, OHchronic coronary ischemia Phase Iwww.compassbiomedical.comadipose-derived regenerative cell(ADRC) therapyCytoriTherapeuticsSan Diego, CAchronic myocardial ischemia(see also heart attack)Phase I/IIwww.cytori.comImaging AgentsProduct Name Sponsor Indication Development Phase
    • Medicines in Development Heart Disease and Stroke 201312Medicines in Development for Heart Disease and StrokeIschemic DisordersProduct Name Sponsor Indication Development PhaseALD-201(bone marrow-derived adultstem cell therapy)CytomedixGaithersburg, MDischemic heart failure Phase Iwww.cytomedix.comALD-301(bone marrow-derived adultstem cell therapy)CytomedixGaithersburg, MDcritical limb ischemia Phase I/IIwww.cytomedix.comALO212(stem cell therapy)Compass BiomedicalCleveland, OHcritical limb ischemia Phase Iwww.compassbiomedical.comallogeneic/autologous adultmesenchymal stem cell therapyBioCardiaSan Carlos, CAischemic heart disorder Phase I/IIwww.biocardia.comautologous stem cell therapy Baxter HealthcareDeerfield, ILmyocardial ischemia Phase IIIwww.baxter.comBendavia™mitochondrial-targetingshort peptideStealth PeptidesNewtown Centre, MAischemic reperfusion in acutemyocardial infarction and heartfailurePhase IIwww.stealthpeptides.comCollategene®beperminogene perplasmid(HGF plasmid)AnGesBethesda, MDMitsubishiTanabe Pharma AmericaJersey City, NJ------------------------------------------------AnGesBethesda, MDcritical limb ischemia(FastTrack)--------------------------------------ischemic heart disorderPhase IIIwww.anges-mg.comwww.mt-pharma-america.com-----------------------------------------Phase Iwww.anges-mg.comERC-124(endometrial blood stem celltherapy)MediStemSan Diego, CAcritical limb ischemia in clinical trialswww.medisteminc.comGenerx®alferminogene tadenovec(Ad5FGF-4)CardiumTherapeuticsSan Diego, CAmyocardial ischemia(FastTrack)Phase IIIwww.cardiumthx.comGS-6615(sodium channel antagonist)Gilead SciencesFoster City, CAischemic heart disease(see also arrhythmia)Phase Iwww.gilead.comJVS-100(stromal cell-derived factor-1)JuventasTherapeuticsCleveland, OHcritical limb ischemia(see also heart failure)Phase IIwww.juventasinc.comMESENDOcombination autologousstem cell therapyTCA CellularTherapyCovington, LAcoronary ischemia, lower limbischemiaPhase IIwww.tcacellulartherapy.com
    • Medicines in Development Heart Disease and Stroke 2013 13Medicines in Development for Heart Disease and StrokeIschemic DisordersProduct Name Sponsor Indication Development PhaseMP4OX SangartSan Diego, CAischemia Phase II completedwww.sangart.comPLX-PAD(stem cell therapy)PluristemTherapeuticsHaifa, Israelcritical limb ischemia(see also peripheral vasculardisease)Phase Iwww.pluristem.comVM202(modified hepatocyte growthfactor gene therapy)ViroMedSeoul, South Koreamyocardial ischemia(see also peripheral vasculardisease)Phase Iwww.viromed.co.krLipid DisordersProduct Name Sponsor Indication Development PhaseALN-PCS(PCSK9 protein inhibitor)Alnylam PharmaceuticalsCambridge, MAThe Medicines CompanyParsippany, NJhypercholesterolemia Phase Iwww.alnylam.comwww.themedicinescompany.comAMG 145(PCSK9 inhibitor mAb)AmgenThousand Oaks, CAheterozygous familialhypercholesterolemia,hypercholesterolemiaPhase Iwww.amgen.comAMR-102(icosapent ethyl/statinfixed-dose combination)AmarinBedminster, NJhyperlipidemia Phase Iwww.amarincorp.comanacetrapib(MK-0859)MerckWhitehouse Station, NJheterozygous familialhypercholesterolemia,hypercholesterolemia(see also atherosclerosis)Phase IIIwww.merck.comARI-3037MO(niacin analog)Arisaph PharmaceuticalsBoston, MAdyslipidemia Phase Iwww.arisaph.comCAT-2003(eicosapentaenoic acid/niacin)Catabasis PharmaceuticalsCambridge, MAsevere hypertriglyceridemia Phase Iwww.catabasis.com
    • Medicines in Development Heart Disease and Stroke 201314Medicines in Development for Heart Disease and StrokeLipid DisordersProduct Name Sponsor Indication Development PhaseCER-001(recombinant HDL)CerenisTherapeuticsAnn Arbor, MIhomozygous familialhypercholesterolemia(see also acute coronary syndrome)Phase IIwww.cerenis.comCER-002(PPAR-delta agonist)CerenisTherapeuticsAnn Arbor, MIdyslipidemia with low HDL Phase Iwww.cerenis.comCER-627(low flushing niacin)CerenisTherapeuticsAnn Arbor, MIdyslipidemia with low HDL Phase Iwww.cerenis.comdiazoxide cholinecontrolled-releaseEssentialisCarlsbad, CAhypertriglyceridemia Phase IIwww.essentialistherapeutics.comEpanova™eicosapentaenoic acid/docosahexaenoic acidOmthera PharmaceuticalsPrinceton, NJhypertriglyceridemia(combination therapy)--------------------------------------hypertriglyceridemia(monotherapy)Phase IIIwww.omthera.com-----------------------------------------Phase II/IIIwww.omthera.comETC-1002(ATP citrate [pro-S]-lyase inhibitor/adenylate kinase stimulator)EsperionTherapeuticsPlymouth, MIdyslipidemia Phase IIwww.esperion.comfenofibrate/simvastatinfixed-dose combinationAbbVieNorth Chicago, ILhyperlipidemia Phase IIIwww.abbvie.comGSK1292263(bombesin receptor agonist)GlaxoSmithKlineRsch. Triangle Park, NChyperlipidemia Phase II completedwww.gsk.comHL-040XC(atorvastatin/losartanfixed-dose combination)HanAll BiopharmaSeoul, South Koreahyperlipidemia(see also hypertension)Phase IIwww.hanall.co.krHPP593(PPAR-delta agonist)High Point PharmaceuticalsHigh Point, NCdyslipidemia Phase Iwww.highpointpharma.comISIS-APOCIIIRx(apolipoprotein C-III inhibitor)Isis PharmaceuticalsCarlsbad, CAhypertriglyceridemia Phase Iwww.isispharm.comK-877(PPAR-alpha agonist)Kowa Pharmaceuticals AmericaMontgomery, ALdyslipidemia Phase Iwww.kowa.co.jpKD026(MTP inhibitor)Kadmon PharmaceuticalsWarrendale, PAdyslipidemia Phase IIwww.kadmon.comKynamro®mipomersenGenzymeCambridge, MAsevere homozygous familialhypercholesterolemiaPhase IIIwww.genzyme.com
    • Medicines in Development Heart Disease and Stroke 2013 15Medicines in Development for Heart Disease and StrokeLipid DisordersProduct Name Sponsor Indication Development PhaseMBX-8025(PPAR-delta agonist)MetabolexHayward, CAdyslipidemia Phase IIwww.metabolex.comMGL-3196(liver-directed thyroid hormonereceptor-ß agonist)Madrigal PharmaceuticalsFort Washington, PAdyslipidemia,hypercholesterolemiaPhase Iwww.madrigalpharma.compradigastat(LCQ908)Novartis PharmaceuticalsEast Hanover, NJfamilial chylomicronemiasyndrome(see also coronary artery disease)--------------------------------------hypertriglyceridemiaPhase IIIwww.novartis.com-----------------------------------------Phase IIwww.novartis.comRN316(PF-04950615)PfizerNew York, NYhypercholesterolemia Phase IIwww.pfizer.comRN317(PF-05335810)PfizerNew York, NYhypercholesterolemia Phase Iwww.pfizer.comSAR236553(anti-PCSK-9 mAb)Regeneron PharmaceuticalsTarrytown, NYSanofi USBridgewater, NJheterozygous familialhypercholesterolemia,hypercholesterolemiaPhase IIIwww.regeneron.comwww.sanofi.comSCH-900271 MerckWhitehouse Station, NJhyperlipidemia Phase II completedwww.merck.comTAP311 Novartis PharmaceuticalsEast Hanover, NJdyslipidemia Phase I completedwww.novartis.comXZK-monascus(HMG-CoA reductase inhibitor)Beijing Peking UniversityWBL BiotechBeijing, Chinahyperlipidemia Phase IIPeripheral Vascular DiseaseProduct Name Sponsor Indication Development PhaseBenlysta®belimumabGlaxoSmithKlineRsch. Triangle Park, NCvasculitis Phase IIIwww.gsk.comBrilinta®ticagrelorAstraZenecaWilmington, DEperipheral arterial disease(see also heart attack)Phase IIIwww.astrazeneca.com
    • Medicines in Development Heart Disease and Stroke 201316Medicines in Development for Heart Disease and StrokePeripheral Vascular DiseaseProduct Name Sponsor Indication Development Phasedefibrotide GentiumVilla Guardia, ItalySigma-Tau PharmaceuticalsGaithersburg, MDtreatment of hepatic venousocclusive disease after stem celltransplantationPhase IIIwww.gentium.comwww.sigmatau.comhuman plasma-derived fibrinolysin GrifolsBarcelona, Spainperipheral vascular occlusivediseasePhase Iwww.grifols.cominclacumab RocheNutley, NJprevention of saphenous veingraft disease(see also acute coronary syndrome,heart attack)Phase IIwww.roche.comK-134(PDE3 inhibitor)Kowa Pharmaceuticals AmericaMontgomery, ALarteriosclerosis obliterans Phase IIwww.kowa.co.jpMABp1(IL-1α mAb)XBiotechAustin, TXvascular restenosis(FastTrack)Phase IIwww.xbiotech.comMultiGeneAngioperipheral arterial disease celltherapyMultiGeneVascular SystemsNesher, Israelperipheral arterial disease Phase I/IIwww.mgvs.co.ilpaclitaxel coated balloon LutonixMinneapolis, MNperipheral arterial disease Phase IIwww.lutonix.compaclitaxel-eluting balloon catheter MEDRAD(Bayer HealthCare)Warrendale, PAstenotic peripheral artery lesions application submittedwww.medrad.comPLX-PAD(stem cell therapy)PluristemTherapeuticsHaifa, Israelintermittent claudication(see also ischemic disorders)Phase IIwww.pluristem.comPRT-201 ProteonTherapeuticsWaltham, MAperipheral arterial disease(see also adjunctive therapies)Phase Iwww.proteontherapeutics.comTSC(trans-sodium crocetinate)Diffusion PharmaceuticalsCharlottesville, VAperipheral arterial disease Phase II completedwww.diffusionpharma.comTV1001(sodium nitrite oral)TheravascCleveland, OHperipheral arterial disease Phase IIwww.theravasc.comVM202(modified hepatocyte growthfactor gene therapy)ViroMedSeoul, South Koreaperipheral arterial disease(see also ischemic disorders)Phase IIwww.viromed.co.kr
    • Medicines in Development Heart Disease and Stroke 2013 17Medicines in Development for Heart Disease and StrokePulmonary Vascular DiseaseProduct Name Sponsor Indication Development PhaseAdcirca™tadalafilEli LillyIndianapolis, INpulmonary hypertension(pediatric)Phase I/IIwww.lilly.comAPD811(prostanoid receptor agonist)Arena PharmaceuticalsSan Diego, CApulmonary arterial hypertension Phase Iwww.arenapharm.comberaprost 314d(single isomer version)UnitedTherapeuticsSilver Spring, MDpulmonary arterial hypertension Phase IIwww.unither.comDA-8159(PDE5 inhibitor)Dong-A PharmaceuticalSeoul, South Koreapulmonary arterial hypertension Phase IIen.donga.co.krINOmax®nitric oxide inhalation(Orphan Drug)IkariaHampton, NJpulmonary arterial hypertension Phase Iwww.ikaria.comLetairis®ambrisentan(Orphan Drug)Gilead SciencesFoster City, CApulmonary hypertension(pediatric)Phase IIwww.gilead.commacitentan(endothelin A receptor antagonist)(Orphan Drug)Actelion PharmaceuticalsSouth San Francisco, CApulmonary arterial hypertension application submittedwww.actelion.comnitric oxide inhalation GeNOWaltham, MApulmonary arterial hypertension Phase IIwww.genollc.comnitrite inhalation(Orphan Drug)Aires PharmaceuticalsSan Diego, CApulmonary arterial hypertension Phase IIwww.airespharma.comriociguat Bayer HealthCare PharmaceuticalsWayne, NJchronic thromboembolicpulmonary hypertensionapplication submittedwww.bayerpharma.comSAR407899(Rho kinase inhibitor)Sanofi USBridgewater, NJpulmonary hypertension Phase Iwww.sanofi.comselexipag Actelion PharmaceuticalsSouth San Francisco, CApulmonary arterial hypertension Phase IIIwww.actelion.comTracleer®bosentanActelion PharmaceuticalsSouth San Francisco, CApulmonary arterial hypertension(pediatric)Phase IIIwww.actelion.comtreprostinil (oral)(sustained-release)UnitedTherapeuticsSilver Spring, MDpulmonary arterial hypertension application submittedwww.unither.com
    • Medicines in Development Heart Disease and Stroke 201318Medicines in Development for Heart Disease and StrokeStrokeProduct Name Sponsor Indication Development Phase3K3A-APC(recombinant humanactivated protein C)ZZ BiotechHouston, TXstroke Phase Iwww.zzbiotech.comALD-401(bone marrow-derived adultstem cell therapy)CytomedixGaithersburg, MDstroke Phase IIwww.cytomedix.comallogeneic mesenchymalbone marrow cell therapyStemedica CellTechnologiesSan Diego, CAischemic stroke Phase I/IIwww.stemedica.comAmpyra™fampridine sustained-releaseAcordaTherapeuticsArdsley, NYpost-stroke deficits Phase IIwww.acorda.combetrixaban Portola PharmaceuticalsSouth San Francisco, CAstroke (prevention) in patientswith atrial fibrillation(see also thrombosis)Phase IIwww.portola.comCNTO-0007(cell therapy)Janssen Research & DevelopmentRaritan, NJischemic stroke Phase Iwww.janssenrnd.comdesmoteplase LundbeckDeerfield, ILischemic stroke(FastTrack)Phase IIIwww.lundbeck.comGM602(nervous system modulator)Genervon BiopharmaceuticalsPasadena, CAacute ischemic stroke Phase IIwww.genervon.comGSK249320(myelin-associated glycoproteinmAb)GlaxoSmithKlineRsch. Triangle Park, NCstroke Phase IIwww.gsk.commetamfetamine Sinapis PharmaJacksonville, FLstroke Phase I completedwww.sinapispharma.comMP-124(PARP inhibitor)MitsubishiTanabe Pharma AmericaJersey City, NJacute ischemic stroke Phase Iwww.mt-pharma.co.jpMultiStem®stem cell therapyAthersysCleveland, OHstroke(see also heart attack)Phase IIwww.athersys.comNA-1(signal transductionpathway inhibitor)NoNO IncToronto, Canadaacute ischemic stroke Phase II completedwww.nonoinc.caNEU 2000 GNT PharmaYongin, South Koreastroke(see also heart attack)Phase I completedwww.gntpharma.com
    • Medicines in Development Heart Disease and Stroke 2013 19Medicines in Development for Heart Disease and StrokeStrokeProduct Name Sponsor Indication Development PhasePF-03049423 PfizerNew York, NYischemic stroke Phase IIwww.pfizer.comRP-1127(NCCA-ATP channel inhibitor)Remedy PharmaceuticalsNew York, NYstroke Phase IIwww.remedypharmaceuticals.comSAR126119(TAFIa inhibitor)Sanofi USBridgewater, NJacute ischemic stroke Phase Iwww.sanofi.comSB623(stem cell therapy)SanBioMountain View, CAstroke Phase I/IIwww.san-bio.comTS01(recombinant complementC1-inactivator-protein)Thrombolytic Science InternationalCambridge, MAstroke Phase Iwww.tsillc.netThrombosisProduct Name Sponsor Indication Development Phasebetrixaban Portola PharmaceuticalsSouth San Francisco, CAthromboembolism (prevention)(see also stroke)Phase IIIwww.portola.comcangrelor The Medicines CompanyParsippany, NJprevention of coronary thrombosisprior to coronary artery bypassgraft (CABG)(see also acute coronary syndrome,coronary artery disease)Phase IIwww.themedicinescompany.comclopidogrel intravenous(MDCO-157)The Medicines CompanyParsippany, NJcoronary thrombosis (prevention) Phase IIIwww.themedicinescompany.comdesirudin IV(intravenous)Canyon PharmaceuticalsColumbia, MDintravenous bolus-onlyadministration in patientsundergoing coronary arterystentingin clinical trialswww.canyonpharma.comedoxaban(oral factor Xa inhibitor)Daiichi SankyoParsippany, NJvenous thromboembolism(prevention), embolism/strokein patients with atrial fibrillation(prevention)Phase IIIwww.daiichisankyo.com
    • Medicines in Development Heart Disease and Stroke 201320Medicines in Development for Heart Disease and StrokeEliquis®apixabanBristol-Myers SquibbPrinceton, NJPfizerNew York, NYprevention of venousthromboembolism, treatment ofvenous thrombosisPhase IIIwww.bms.comwww.pfizer.comGCC-4401 Green CrossYongin, South Koreacoronary thrombosis Phase I completedwww.greencross.co.krIprivask®desirudin SC(subcutaneous)Canyon PharmaceuticalsColumbia, MDthromboembolism in patients withsuspected heparin-inducedthrombocytopenia (prevention andtreatment), venousthromboembolism in high-risksurgical and medical patients(prevention)in clinical trialswww.canyonpharma.comISIS-FXIRx(factor XI inhibitor)Isis PharmaceuticalsCarlsbad, CAvenous thromboembolism Phase Iwww.isispharm.comPradaxa®dabigatran etexilateBoehringer Ingelheim PharmaceuticalsRidgefield, CTacute treatment and reductionin the risk of recurrence of deepvenous thrombosis and pulmonaryembolismPhase IIIwww.boehringer-ingelheim.comREG2(pegnivacogin subcutaneous)Regado BiosciencesBasking Ridge, NJvenous thrombosis Phase Iwww.regadobio.comvorapaxar(thrombin/PAR-1 receptorantagonist)MerckWhitehouse Station, NJarterial thrombosis (prevention)(FastTrack)(see also acute coronary syndrome)Phase IIIwww.merck.comXarelto®rivaroxabanBayer HealthCare PharmaceuticalsWayne, NJJanssen Research & DevelopmentRaritan, NJvenous thromboembolism(pediatric)(see also acute coronary syndrome,other)Phase Iwww.bayerpharma.comwww.janssenrnd.comOtherProduct Name Sponsor Indication Development PhaseACZ885(canakinumab)Novartis PharmaceuticalsEast Hanover, NJsecondary prevention ofcardiovascular events(see also atherosclerosis)Phase IIIwww.novartis.comThrombosisProduct Name Sponsor Indication Development Phase
    • Medicines in Development Heart Disease and Stroke 2013 21Medicines in Development for Heart Disease and Strokealeglitazar(PPAR alpha/gamma co-agonist)RocheNutley, NJprevention of cardiovasculardisorders in patients with type 2diabetesPhase IIIwww.roche.comALN-TTRsc(prealbumin inhibitor)Alnylam PharmaceuticalsCambridge, MAfamilial amyloidoticcardiomyopathyPhase Iwww.alnylam.comBydureon®exenatide extended-releasefor injectable suspensionAstraZenecaWilmington, DEBristol-Myers SquibbPrinceton, NJcardiovascular outcomes Phase IIIwww.astrazeneca.comwww.bms.comcaplacizumab(Orphan Drug)AblynxGhent, Belguimthrombotic thrombocytopenicpurpuraPhase IIwww.ablynx.comCardiaPill®aspirin/lisinopril/lovastatinCardioPharmaWilmington, NCcardiovascular disorders in clinical trialswww.cardio-pharma.comcardiovascular disease medicine Eli LillyIndianapolis, INcardiovascular disease Phase Iwww.lilly.comdroxidopa(Orphan Drug)ChelseaTherapeuticsCharlotte, NCorthostatic hypotension(FastTrack)application submittedwww.chelseatherapeutics.comevacetrapib Eli LillyIndianapolis, INprevention of cardiovascular eventsin high-risk vascular diseasePhase IIIwww.lilly.comForxiga®dapagliflozinAstraZenecaWilmington, DEBristol-Myers SquibbPrinceton, NJcardiovascular outcomes Phase IIIwww.astrazeneca.comwww.bms.comixmyelocel-T(stem cell therapy)Aastrom BiosciencesAnn Arbor, MIdilated cardiomyopathy Phase IIwww.aastrom.comMEK162(MEK inhibitor)Novartis PharmaceuticalsEast Hanover, NJNoonan syndrome hypertrophiccardiomyopathyPhase IIwww.novartis.comOnglyza®saxagliptinAstraZenecaWilmington, DEBristol-Myers SquibbPrinceton, NJcardiovascular outcomes Phase IIIwww.astrazeneca.comwww.bms.comPA8140(aspirin 81mg/omeprazole 40mg)POZENChapel Hill, NCsecondary prevention ofcardiovascular and cerebrovasculardisease in patients at risk foraspirin-induced ulcersapplication submittedwww.pozen.comOtherProduct Name Sponsor Indication Development Phase
    • Medicines in Development Heart Disease and Stroke 201322PA32540(aspirin 325mg/omeprazole 40mg)POZENChapel Hill, NCsecondary prevention ofcardiovascular and cerebrovasculardisease in patients at risk foraspirin-induced ulcersapplication submittedwww.pozen.comRX-10001(lipid modulator)Resolvyx PharmaceuticalsCambridge, MAcardiovascular disorders Phase I completedwww.resolvyx.comT89(herbal medicine product)Tasly PharmaceuticalsRockville, MDangina pectoris Phase IIIwww.tasly.comVascana™nitroglycerin topicalMediQuestTherapeuticsMaple Valley, WARaynaud’s disease Phase IIIwww.mqti.comVyndaqel®tafamidis megluminePfizerNew York, NYtransthyretin familial amyloidcardiomyopathyPhase IIIwww.pfizer.comXarelto®rivaroxabanBayer HealthCare PharmaceuticalsWayne, NJJanssen Research & DevelopmentRaritan, NJprevention of cardiovascular eventssecondary to chronic heart failure,coronary or peripheral arterydisease, or atrial fibrillation(FastTrack)(see also acute coronary syndrome,thrombosis)Phase IIIwww.bayerpharma.comwww.janssenrnd.comMedicines in Development for Heart Disease and StrokeOtherProduct Name Sponsor Indication Development PhaseThe content of this report has been obtained through public, government and industry sources, and the Adis “R&D Insight” data-base based on the latest information. Report current as of May 22, 2013. The medicines in this report include medicines beingdeveloped by U.S. based companies conducting trials in the United States and abroad, PhRMA-member companies conductingtrials in the United States and abroad, and foreign companies conducting clinical trials in the United States. The information inthis report may not be comprehensive. For more specific information about a particular product, contact the individual companydirectly or go to www.clinicaltrials.gov. The entire series of Medicines in Development is available on PhRMA’s website.A publication of PhRMA’s Communications & Public Affairs Department. (202) 835-3460www.phrma.org | www.innovation.org | www.pparx.orgProvided as a Public Service by PhRMA. Founded in 1958 as the Pharmaceutical Manufacturers Association.Copyright © 2013 by the Pharmaceutical Research and Manufacturers of America. Permission to reprint is awarded if propercredit is given.Pharmaceutical Research and Manufacturers of America • 950 F Street, NW, Washington, DC 20004
    • Medicines in Development Heart Disease and Stroke 2013 23Glossaryadjunctive therapy—Auxiliary treatmentthat is secondary to the main treatment.angina pectoris—Chest pain, usuallycaused by “myocardial ischemia,” a lowsupply of oxygen to the heart muscleresulting from hardening, narrowing,and sometimes spasm of the coronaryarteries.application submitted—An applicationfor marketing has been submitted by thecompany to the Food and Drug Admin-istration (FDA).arrhythmia—Abnormal heart rhythm,usually detected by an electrocardio-gram. Arrhythmias can be caused byseveral factors, such as coronary arterydisease, heart valve problems or hyper-thyroidism.arteriosclerosis obliterans—An alter-native term for peripheral vasculardisease.atherosclerosis—A common diseasein which deposits of plaque containingcalcium and fatty substances, such ascholesterol, are formed within the innerlayers of the arteries. It is a conditionthat progresses over decades, chieflyaffecting the arteries of the heart, brainand extremities. Its complications includeheart attacks and strokes.atrial fibrillation—Very fast electricaldischarge patterns that make the heart’satria contract extremely rapidly, whichcauses the ventricles to contract fasterand less efficiently than normal. As aresult, inadequate amounts of blood arepumped out of the heart, blood pressurefalls, and heart failure may occur.bypass graft—A vein or artery graft thatbypasses blockage in an artery.cardiomyopathy—A type of heartdisease in which the heart muscle isabnormally enlarged, thickened and/orstiffened. As a result, the heart muscle’sability to pump blood is usually impaired.cardiovascular—Of or relating to theheart and blood vessels.coronary artery disease—A conditioncaused by atherosclerosis of the arteriesthat supply the heart.critical limb ischemia (CLI)—CLI is asevere obstruction of the arteries thatseriously decreases blood flow to theextremities (arms, hands, legs, feet) andhas progressed to the point of severepain and even skin ulcers or sores. Thepain, called “rest pain,” caused by CLIcan wake up a person at night. CLI isa very severe condition of peripheralarterial disease and needs comprehen-sive treatment by a vascular surgeon orspecialist.deep vein thrombosis—Blood clottingwithin the deep-lying veins, often in thelegs or pelvic veins.dyslipidemia—A condition marked byabnormal concentrations of lipids orlipoproteins in the blood.embolism—The obstruction of a bloodvessel by a foreign substance or a bloodclot. Foreign substances that can causeembolism include an air bubble, amni-otic fluid, a globule of fat, a clump ofbacteria, chemicals, and drugs. Bloodclots are the most common cause ofembolism. The term “embolus” refers tothe substance or clot that is obstructingthe blood vessel, while “embolism” refersto the process by which that happens.Fast Track—A process designed tofacilitate the development and expeditethe review of drugs to treat seriousdiseases and fill an unmet medical need.The status is assigned by the U.S. Foodand Drug Administration. The purposeis to get important new drugs to thepatient earlier. Fast Track addresses abroad range of serious diseases. Gener-ally, determining factors include whetherthe drug will have an impact on suchfactors as survival, day-to-day function-ing, or the likelihood that the disease, ifleft untreated, will progress from a lesssevere condition to a more serious one.Filling an unmet medical need is definedas providing a therapy where none existsor providing a therapy which may bepotentially superior to existing therapy.Once a drug receives Fast Track designa-tion, early and frequent communicationbetween the FDA and a drug company isencouraged throughout the entire drugdevelopment and review process. Thefrequency of communication assures thatquestions and issues are resolved quickly,often leading to earlier drug approvaland access by patients.genotype—The genetic constitution(genome) of a cell, an individual, or anorganism. The genotype of a person isher or his genetic makeup. It can pertainto all genes or to a specific gene.HDL—High-density lipoprotein, some-times called “good cholesterol.”heart attack (myocardial infarction)—Apart of the heart muscle (myocardium)dies as a result of blood and oxygendeprivation.heart failure—The end result of manydifferent types of heart disease. Theheart cannot pump blood out normally.This results in congestion (water and saltretention) in the lungs, swelling in theextremities, and reduced blood flow tobody tissues.hemodialysis—A medical procedure thatuses a special machine (a dialysis ma-chine) to filter waste products from theblood and to restore normal constituentsto it.hypercholesterolemia—The presence ofan abnormally large amount of cho-lesterol in the cells and plasma of thecirculating blood.hyperlipidemia—A group of metabolicdisorders characterized by high levels oflipids (fatty substances, including choles-terol) in the blood. Hyperlipidemia is arisk factor for accelerated atherosclerosisand premature heart attacks.hypertension (high blood pressure)—Persistent elevation of blood pressureabove the normal range while the heartis in systolic (contracting) or diastolic(relaxed) mode. Uncontrolled, chronic
    • Medicines in Development Heart Disease and Stroke 201324Glossaryhypertension strains the heart, damagesarteries and creates a greater risk ofheart attack, stroke and kidney problems.hypertriglyceridemia—An elevatedtriglyceride concentration in the blood.hypotension—A sudden fall in bloodpressure. It may be caused by hypovo-lemia resulting from the excessive useof diuretics, vasodilators, or other typesof drugs, dehydration, or prolonged bedrest. The disorder may be associatedwith Addison’s disease, atherosclerosis(build-up of fatty deposits in the arter-ies), diabetes, and certain neurologicaldisorders. Symptoms, which generallyoccur after sudden standing, include diz-ziness, light-headedness, blurred vision,and the temporary loss of consciousness.imaging agent—A substance used toenhance images of organs and spaces inthe body.intermittent claudication—The mostprominent symptom of peripheral arte-rial disease (PAD). It occurs in one-thirdto one-half of PAD patients. Claudica-tion refers to the pain that occurs in PADpatients when they exercise, particularlyduring walking, which is relieved only byrest. Leg pain occurs in one leg in 40percent of patients and in both legs in60 percent of patients.ischemia—Insufficient supply of blood toan organ or tissue, which can cause or-gan damage such as an ischemic stroke.lipids—A group of fatty substances thatincludes triglycerides (the principal formsof fat in body fat), phospholipids (im-portant constituents of cell membranes),and sterols (such as cholesterol).peripheral vascular disease—Theobstruction of blood supply to the ex-tremities, particularly the legs, caused byatherosclerosis.PET imaging—Positron emission tomog-raphy.Phase I—Safety testing and pharmaco-logical profiling in humans.Phase II—Effectiveness testing inhumans.Phase III—Extensive clinical trials inhumans.preeclampsia—A condition in pregnantwomen characterized by high bloodpressure and high levels of protein inurine.pulmonary hypertension—High bloodpressure in the arteries supplying thelungs due to increased resistance toblood flow through the lungs.Raynaud’s disease—A circulatory disor-der caused by insufficient blood supplyto the hands and feet, resulting in cya-nosis, numbness, pain, and, in extremecases, gangrene.reperfusion injury—Refers to myocar-dial, vascular, or electro-physiologicaldysfunction that is induced by therestoration of blood flow to previouslyischemic tissue.restenosis—A condition where an arteryplugs up again following treatment toopen it up.stent—A metal device that is used tohold tissue in place. For example, a stentcan keep blood vessels open after a sur-gical procedure or heart catheterization.stroke—Usually caused by atheroscle-rosis. It results in death or serious braindamage, such as paralysis or loss ofspeech. An ischemic stroke is causedby blocked or narrowed arteries thatprevent sufficient blood and oxygen fromreaching the brain.thromboembolism—Blockage of a bloodvessel by a fragment that has brokenoff and been carried from a thrombus(blood clot) elsewhere in the circulation.thrombosis—The formation of a bloodclot within the heart or a blood vessel.
    • The Drug Discovery, Development and Approval ProcessThe U.S. system of new drug approvals isperhaps the most rigorous in the world.It takes 10-15 years, on average, for an experi-mental drug to travel from lab to U.S. patients,according to the Tufts Center for the Study ofDrug Development. Only five in 5,000 com-pounds that enter preclinical testing make it tohuman testing. And only one of those five isapproved for sale.On average, it costs a company $1.2 billion,including the cost of failures, to get one newmedicine from the laboratory to U.S. patients,according to a recent study by the Tufts Centerfor the Study of Drug Development.Once a new compound has been identified inthe laboratory, medicines are usually developedas follows:Preclinical Testing. A pharmaceutical companyconducts laboratory and animal studies to showbiological activity of the compound against thetargeted disease, and the compound is evalu-ated for safety.Investigational New Drug Application (IND).After completing preclinical testing, a com-pany files an IND with the U.S. Food and DrugAdministration (FDA) to begin to test the drugin people. The IND shows results of previousexperiments; how, where and by whom the newstudies will be conducted; the chemical structureof the compound; how it is thought to work inthe body; any toxic effects found in the animalstudies; and how the compound is manufac-tured. All clinical trials must be reviewed and ap-proved by the Institutional Review Board (IRB)where the trials will be conducted. Progressreports on clinical trials must be submitted atleast annually to FDA and the IRB.Clinical Trials, Phase I—Researchers test thedrug in a small group of people, usually between20 and 80 healthy adult volunteers, to evaluateits initial safety and tolerability profile, deter-mine a safe dosage range, and identify potentialside effects.Clinical Trials, Phase II—The drug is givento volunteer patients, usually between 100 and300, to see if it is effective, identify an optimaldose, and to further evaluate its short-termsafety.Clinical Trials, Phase III—The drug is given to alarger, more diverse patient population, ofteninvolving between 1,000 and 3,000 patients(but sometime many more thousands), to gener-ate statistically significant evidence to confirmits safety and effectiveness. They are the lon-gest studies, and usually take place in multiplesites around the world.New Drug Application (NDA)/Biologic LicenseApplication (BLA). Following the completionof all three phases of clinical trials, a companyanalyzes all of the data and files an NDA or BLAwith FDA if the data successfully demonstrateboth safety and effectiveness. The applicationscontain all of the scientific information that thecompany has gathered. Applications typicallyrun 100,000 pages or more.Approval. Once FDA approves an NDA or BLA,the new medicine becomes available for physi-cians to prescribe. A company must continueto submit periodic reports to FDA, includingany cases of adverse reactions and appropriatequality-control records. For some medicines,FDA requires additional trials (Phase IV) toevaluate long-term effects.Discovering and developing safe and effectivenew medicines is a long, difficult, and expensiveprocess. PhRMA member companies invested anestimated $48.5 billion in research and develop-ment in 2012.Developing a new medicine takes an average of 10-15 years;For every 5,000-10,000 compounds in the pipeline, only 1 is approved.The Drug Development and Approval ProcessPRE-DISCOVERYDRUG DISCOVERY PRECLINICAL CLINICAL TRIALS FDA REVIEW LG-SCALE MFG3 – 6 YEARS 6– 7 YEARS0.5– 2YEARS100–300 1,000–3,00020–80PHASE2PHASE3PHASE1INDSUBMITTEDNDASUBMITTEDPHASE4:POST-MARKETINGSURVEILLANCENUMBER OF VOLUNTEERSONE FDA-APPROVEDDRUG5,000 –10,000COMPOUNDS250 5Drug Discovery and Development: A LONG, RISKY ROAD