When to Intervene in Chronic Valvular Heart Disease 2019 ...
Heart Disease Drug Development
Transcript of Heart Disease Drug Development
2013 R
EPORT
Biopharmaceutical research companies are developing 215 medicines for two of the leading causes of death in Ameri-cans—heart disease and stroke. Medi-cines have helped cut deaths from these diseases by 30 percent between 2001 and 2011, and in 2008 stroke dropped to the fourth leading cause of death after being the third for more than 50 years. This progress is in large part due to innovative medicines.
Despite this progress, heart disease and stroke persist as key public health chal-lenges. According to the American Heart Association, every 39 seconds an Ameri-can dies from cardiovascular disease, and more than 83 million Americans have at least one type of the disease. These diseases cost our society more than $312 billion 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 and ischemic disorders. Many of the potential
medicines use cutting-edge technologies and new scientific approaches, such as:
• A gene therapy that uses a patient’s own cells to treat heart failure.
• A medicine that blocks the transfer of good (HDL) cholesterol to bad (LDL).
• A genetically-engineered medicine that dissolves clots to treat stroke.
All of the medicines are either in clinical trials or awaiting review by the Food and Drug Administration. A glossary of terms begins on page 24. Links to sponsor company websites provide more informa-tion on the potential products.
For information on the current innovative products in the pipeline for cardiovascular disease and the value of medicines for patients and our healthcare system, please see Medicines in Development for Heart Disease and Stroke 2013—Overview.
Biopharmaceutical Research Companies Are Developing More Than 200 Medicines for Cardiovascular Disease
MeDiCines in DevelopMenT
Heart Disease and strokeA Report on Cardiovascular Disease
presented by america’s biopharmaceutical research companies
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Application Submitted
Phase III
Phase II
Phase I
Medicines in Development For Heart Disease and stroke
83.6 million americans suffer From cardiovascular disease
more than 700,000 die each year
Medicines in Development heart disease and stroke 20132
medicines 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 Syndrome
Product Name Sponsor Indication Development Phase*
cangrelor The Medicines CompanyParsippany, NJ
acute coronary syndrome(see also coronary artery disease, thrombosis)
Phase Iwww.themedicinescompany.com
CER-001(recombinant HDL)
Cerenis TherapeuticsAnn Arbor, MI
acute coronary syndrome(see also lipid disorders)
Phase IIwww.cerenis.com
gevokizumab ServierParis, FranceXOMABerkeley, CA
acute coronary syndrome Phase IIwww.servier.comwww.xoma.com
inclacumab(RG1512)
RocheNutley, NJ
acute coronary syndrome(see also heart attack, peripheral vascular disease)
Phase IIwww.roche.com
losmapimod(p38 kinase inhibitor)
GlaxoSmithKlineRsch. Triangle Park, NC
acute coronary syndrome Phase IIwww.gsk.com
PF-06282999 PfizerNew York, NY
acute coronary syndrome Phase Iwww.pfizer.com
REG1(anivamersen-pegnivacogin intravenous)
Regado BiosciencesBasking Ridge, NJ
acute coronary syndrome Phase IIwww.regadobio.com
RVX-208(BET protein inhibitor)
ResverlogixCalgary, Canada
acute coronary syndrome(see also atherosclerosis)
Phase IIwww.resverlogix.com
vorapaxar(thrombin/PAR-1 receptor antagonist)
MerckWhitehouse Station, NJ
acute coronary syndrome (prevention) (Fast Track)(see also thrombosis)
Phase IIIwww.merck.com
VT-111a Viron TherapeuticsOntario, Canada
acute coronary syndrome Phase IIwww.vironinc.com
Vytorin®
ezetimibe/simvastatin fixed-dose combination
MerckWhitehouse Station, NJ
acute coronary syndrome Phase IIIwww.merck.com
Xarelto®
rivaroxabanBayer HealthCare PharmaceuticalsWayne, NJJanssen Research & DevelopmentRaritan, NJ
acute coronary syndrome(Fast Track)(see also thrombosis, other)
application submittedwww.bayerpharma.comwww.janssenrnd.com
Medicines in Development heart disease and stroke 2013 3
medicines in development for heart disease and stroke
Adjunctive Therapies, Revascularization
Product Name Sponsor Indication Development Phase
ATryn®
antithrombin(recombinant)(Orphan Drug)
rEVO BiologicsFramingham, MA
heparin resistance in patients undergoing coronary artery bypass graft (CABG) surgery (see also hypertension)--------------------------------------heparin resistance in patients undergoing CABG surgery in neonates
Phase IIIwww.gtc-bio.com
-----------------------------------------Phase Iwww.gtc-bio.com
CMX-2043(proto-oncogene protein C AKT modulator)
IschemixMaynard, MA
prevention of ischemia-reperfusion injury in patients undergoing percutaneous coronary intervention (PCI)
Phase IIwww.ischemix.com
myolimus-eluting stent Elixir MedicalSunnyvale, CA
coronary artery restenosis (prevention)
Phase Iwww.elixirmedical.com
novolimus-eluting coronary stent Elixir MedicalSunnyvale, CA
coronary artery restenosis (prevention)
in clinical trialswww.elixirmedical.com
PRT-201 Proteon TherapeuticsWaltham, MA
vascular access for hemodialysis(see also peripheral vascular disease)
Phase IIwww.proteontherapeutics.com
ranolazine Gilead SciencesFoster City, CA
incomplete revascularization in patients who undergo PCI
Phase IIIwww.gilead.com
sirolimus-eluting coronary stent REVA MedicalSan Diego, CA
coronary artery restenosis in clinical trialswww.teamreva.com
sirolimus-eluting coronary stent Svelte Medical SystemsNew Providence, NJ
ischemic heart disorder Phase I/IIwww.sveltemedical.com
SRM003(endothelial cell therapy)
Shire PharmaceuticalsWayne, PA
prevention of peripheral vascular complications in patients undergoing arteriovenous access procedures for hemodialysis
Phase IIwww.shire.com
Medicines in Development heart disease and stroke 20134
medicines in development for heart disease and stroke
Arrhythmia, Atrial Fibrillation
Product Name Sponsor Indication Development Phase
ARM036 ARMGO PharmaTarrytown, NY
catecholaminergic polymorphic ventricular tachycardia type 1(see also heart failure)
Phase IIwww.armgo.com
azimilide Forest LaboratoriesNew York, NY
ventricular arrhythmia Phase IIIwww.frx.com
BMS-919373(Ikur antagonist)
Bristol-Myers SquibbPrinceton, NJ
atrial fibrillation Phase Iwww.bms.com
danegaptide(ZP1609)
Zealand PharmaCopenhagen, Denmark
atrial fibrillation Phase Iwww.zealandpharma.com
GS-6615(sodium channel antagonist)
Gilead SciencesFoster City, CA
arrhythmia(see also ischemic disorders)
Phase Iwww.gilead.com
ISIS-CRPRx(C-reactive protein inhibitor)
Isis PharmaceuticalsCarlsbad, CA
paroxysmal atrial fibrillation Phase Iwww.isispharm.com
OPC-108459 Otsuka America PharmaceuticalRockville, MD
paroxysmal and persistent atrial fibrillation
Phase Iwww.otsuka.com
ranolazine/dronedarone fixed-dose combination
Gilead SciencesFoster City, CA
paroxysmal atrial fibrillation Phase IIwww.gilead.com
vanoxerine ChanRxCleveland, OH
atrial fibrillation Phase IIwww.chanrx.com
vernakalant(oral)
Cardiome PharmaVancouver, Canada
atrial fibrillation Phase IIwww.cardiome.com
Atherosclerosis
Product Name Sponsor Indication Development Phase
ACP-501(rhLCAT)
AlphaCore PharmaAnn Arbor, MI
atherosclerosis(see also coronary artery disease)
Phase Iwww.alphacorepharma.com
ACZ885(canakinumab)
Novartis PharmaceuticalsEast Hanover, NJ
atherosclerosis in patients with type 2 diabetes(see also other)
Phase IIwww.novartis.com
anacetrapib(MK-0859)
MerckWhitehouse Station, NJ
atherosclerosis(see also lipid disorders)
Phase IIIwww.merck.com
BMS-852927(LXR modulator)
Bristol-Myers SquibbPrinceton, NJ
atherosclerosis Phase Iwww.bms.com
Medicines in Development heart disease and stroke 2013 5
medicines in development for heart disease and stroke
Atherosclerosis
Product Name Sponsor Indication Development Phase
BMS-962476(PCSK9 adnectin)
Bristol-Myers SquibbPrinceton, NJ
atherosclerosis Phase Iwww.bms.com
CSL-112(cholesterol modulator)
CSLVictoria, Australia
atherosclerosis Phase IIwww.csl.com.au
darapladib(Lp-PLA2 inhibitor)
GlaxoSmithKlineRsch. Triangle Park, NC
atherosclerosis Phase IIIwww.gsk.com
ISIS-APOARx(antisense RNA inhibitor)
Isis PharmaceuticalsCarlsbad, CA
atherosclerosis Phase Iwww.isispharm.com
rilapladib GlaxoSmithKlineRsch. Triangle Park, NC
atherosclerosis Phase II completedwww.gsk.com
RVX-208(BET protein inhibitor)
ResverlogixCalgary, Canada
atherosclerosis(see also acute coronary syndrome)
Phase IIwww.resverlogix.com
Tekturna®
aliskirenNovartis PharmaceuticalsEast Hanover, NJ
atherosclerosis in coronary artery disease(see also heart failure, hypertension)
Phase IIIwww.novartis.com
VB201(IL-12 subunit p40 inhibitor)
VBL TherapeuticsOr Yehuda, Israel
atherosclerosis Phase IIwww.vblrx.com
Coronary Artery Disease
Product Name Sponsor Indication Development Phase
ACP-501(rhLCAT)
AlphaCore PharmaAnn Arbor, MI
coronary artery disease(see also atherosclerosis)
Phase Iwww.alphacorepharma.com
cangrelor The Medicines CompanyParsippany, NJ
coronary artery disease in patients requiring percutaneous coronary intervention (PCI)(see also acute coronary syndrome, thrombosis)
Phase IIIwww.themedicinescompany.com
cardiovascular therapy releasing balloon(drug-coated Angiosculpt®)
AngioScoreFremont, CA
coronary artery restenosis Phase IIwww.angioscore.com
coronary artery disease gene therapy
BioCardiaSan Carlos, CA
coronary artery disease Phase IIwww.biocardia.com
Medicines in Development heart disease and stroke 20136
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Coronary Artery Disease
Product Name Sponsor Indication Development Phase
fibroblast growth factor-1 (FGF-1) CardioVascular BioTherapeuticsLas Vegas, NV
severe coronary heart disease Phase IIwww.cvbt.com
LT-1951(oligo-L-arginine)
Lumen TherapeuticsMenlo Park, CA
coronary artery restenosis Phase I/IIwww.lumentherapeutics.com
pradigastat(LCQ908)
Novartis PharmaceuticalsEast Hanover, NJ
coronary artery disease(see also lipid disorders)
Phase IIwww.novartis.com
RG7652(PCSK9 protein inhibitor)
GenentechSouth San Francisco, CA
coronary heart disease Phase IIwww.gene.com
Heart Attack (Myocardial Infarction)
Product Name Sponsor Indication Development Phase
abciximab(intracoronary infusion)
Atrium Medical CorporationHudson, NH
myocardial infarction(new delivery system)
Phase IIIwww.atriummed.com
adipose-derived regenerative cell (ADRC) therapy
Cytori TherapeuticsSan Diego, CA
acute myocardial infarction(see also ischemic disorders)
Phase IIwww.cytori.com
AMR-001(stem cell therapy)
Amorcyte (NeoStem)New York, NY
myocardial infarction Phase Iwww.neostem.com
BB3(HGF mimetic)
Angion BiomedicaUniondale, NY
acute myocardial infarction Phase IIwww.angion.com
Brilinta®
ticagrelorAstraZenecaWilmington, DE
prior myocardial infarction(see also peripheral vascular disease)
Phase IIIwww.astrazeneca.com
CAP-1002(allogeneic cardiosphere-derived stem cell therapy)
CapricorBeverly Hills, CA
myocardial infarction Phase I/IIwww.capricor.com
inclacumab RocheNutley, NJ
myocardial infarction(see also acute coronary syndrome, peripheral vascular disease)
Phase IIwww.roche.com
ischemic tolerant allogeneic mesenchymal stem cell therapy
Stemedica Cell TechnologiesSan Diego, CA
acute myocardial infarction Phase IIwww.stemedica.com
mesenchymal stem cell therapy MesoblastNew York, NY
heart attack(see also heart failure)
Phase IIwww.mesoblast.com
Medicines in Development heart disease and stroke 2013 7
medicines in development for heart disease and stroke
Heart Attack (Myocardial Infarction)
Product Name Sponsor Indication Development Phase
MultiStem®
stem cell therapyAthersysCleveland, OH
acute myocardial infarction(see also stroke)
Phase I completedwww.athersys.com
NEU 2000 GNT PharmaYongin, South Korea
myocardial infarction(see also stroke)
Phase I completedwww.gntpharma.com
Prochymal®remestemcel-L
Osiris TherapeuticsColumbia, MD
acute myocardial infarction Phase IIwww.osiris.com
Heart Failure (Congestive Heart Failure)
Product Name Sponsor Indication Development Phase
albiglutide(GSK716155)
GlaxoSmithKlineRsch. Triangle Park, NC
heart failure Phase II completedwww.gsk.com
ANX-042(natriuretic-peptide)
AnexonCambridge, MA
acute decompensated heart failure Phase Iwww.anexonrx.com
ARM036 ARMGO PharmaTarrytown, NY
chronic heart failure(see also arrhythmia)
Phase IIwww.armgo.com
BAY 868050(vasopressin receptor antagonist)
Bayer HealthCare PharmaceuticalsWayne, NJ
heart failure Phase Iwww.bayerpharma.com
BAY 948862(mineralocorticoid receptor [MR] antagonist)
Bayer HealthCare PharmaceuticalsWayne, NJ
chronic heart failure Phase IIwww.bayerpharma.com
BAY 1021189(guanylate cyclase stimulant)
Bayer HealthCare PharmaceuticalsWayne, NJ
heart failure Phase Iwww.bayerpharma.com
BAY 1067197(partial adenosine A1 agonist)
Bayer HealthCare PharmaceuticalsWayne, NJ
heart failure Phase Iwww.bayerpharma.com
BMS-986046(PEG-relaxin)
AmbrxLa Jolla, CABristol-Myers SquibbPrinceton, NJ
heart failure Phase Iwww.ambrx.comwww.bms.com
bucindolol companion diagnostic ARCA biopharmaBroomfield, COLabCorpBurlington, NC
heart failure (diagnosis) in clinical trialswww.arcabiopharma.comwww.labcorp.com
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cenderitide Nile TherapeuticsSan Mateo, CA
acute heart failure (Fast Track)--------------------------------------chronic heart failure(Fast Track)
Phase IIwww.nilethera.com-----------------------------------------Phase Iwww.nilethera.com
CLP-1001(sodium-potassium-chloride symporter inhibitor)
Sorbent TherapeuticsSunnyvale, CA
congestive heart failure in patients with chronic kidney disease
Phase IIwww.sorbent.com
CXL-1020(nitroxyl donor)
Cardioxyl PharmaceuticalsChapel Hill, NC
acute decompensated heart failure Phase IIwww.cardioxyl.com
Gencaro™bucindolol
ARCA biopharmaBroomfield, CO
genotype-defined heart failure(Fast Track)
application submittedwww.arcabiopharma.com
GGF2(recombinant neuregulin-1)
Acorda TherapeuticsArdsley, NY
heart failure(Fast Track)
Phase Iwww.acorda.com
GSK2849466(selective androgen receptor modulator)
GlaxoSmithKlineRsch. Triangle Park, NC
heart failure Phase Iwww.gsk.com
JNJ-39588146 Janssen Research & DevelopmentRaritan, NJ
heart failure Phase IIwww.janssenrnd.com
JVS-100(stromal cell-derived factor-1)
Juventas TherapeuticsCleveland, OH
heart failure(see also ischemic disorders)
Phase IIwww.juventasinc.com
LCZ696(ARB/NEP inhibitor)
Novartis PharmaceuticalsEast Hanover, NJ
heart failure(see also hypertension)
Phase IIIwww.novartis.com
mesenchymal stem cell therapy MesoblastNew York, NY
congestive heart failure(see also heart attack)
Phase IIwww.mesoblast.com
Mydicar®
SERCA 2a gene therapyCelladonSan Diego, CA
advanced (Class III/IV) heart failure(Fast Track)--------------------------------------chronic heart failure
Phase IIwww.celladon.net-----------------------------------------Phase II completedwww.celladon.net
MyoCell®stem cell therapy
BioheartSunrise, FL
heart failure Phase II/IIIwww.bioheartinc.com
MyoCell® SDF1muscle stem cell therapy(second-generation)
BioHeartSunrise, FL
congestive heart post myocardial infarction
Phase Iwww.bioheartinc.com
Heart Failure (Congestive Heart Failure)
Product Name Sponsor Indication Development Phase
Medicines in Development heart disease and stroke 2013 9
medicines in development for heart disease and stroke
omecamtiv mecarbil AmgenThousand Oaks, CACytokineticsSouth San Francisco, CA
heart failure Phase IIwww.amgen.comwww.cytokinetics.com
PL-3994(natriuretic-peptide)
Palatin TechnologiesCranbury, NJ
congestive heart failure(see also hypertension)
Phase IIwww.palatin.com
recombinant humanneuregulin-1 beta
ZensunShanghai, China
stable chronic heart failure Phase IIwww.zensun.com
serelaxin(RLX030)
Novartis PharmaceuticalsEast Hanover, NJ
acute heart failure(Fast Track)--------------------------------------chronic heart failure
Phase IIIwww.novartis.com-----------------------------------------Phase IIwww.novartis.com
Tekturna®
aliskirenNovartis PharmaceuticalsEast Hanover, NJ
acute decompensated heart failure(see also atherosclerosis, hypertension)--------------------------------------reduction of cardiovascular death/hospitalization in chronic heart failure patients
Phase III completedwww.novartis.com
-----------------------------------------Phase IIIwww.novartis.com
TRV027(angiotensin type 1 receptorantagonist)
Forest LaboratoriesNew York, NYTrevenaKing of Prussia, PA
acute heart failure (late-stage disease)
Phase IIwww.frx.comwww.trevenainc.com
ularitide CardiorentisZug, Switzerland
acute heart failure Phase IIIwww.cardiorentis.ch
urocortin 2 Neurocrine BiosciencesSan Diego, CA
congestive heart failure Phase IIwww.neurocrine.com
Hypertension (High Blood Pressure)
Product Name Sponsor Indication Development Phase
AHU377(neprilysin inhibitor)
Novartis PharmaceuticalsEast Hanover, NJ
essential hypertension Phase IIwww.novartis.com
ATryn®
antithrombin(recombinant)
rEVO BiologicsFramingham, MA
preeclampsia(see also adjunctive therapies)
Phase IIwww.gtc-bio.com
Heart Failure (Congestive Heart Failure)
Product Name Sponsor Indication Development Phase
Medicines in Development heart disease and stroke 201310
medicines in development for heart disease and stroke
candesartan cilexetil/nifedipine fixed-dose combination
Bayer HealthCare PharmaceuticalsWayne, NJ
essential hypertension Phase IIIwww.bayerpharma.com
digoxin immune Fab (DIF)(Orphan Drug)
Glenveigh PharmaceuticalsChattanooga, TN
preeclampsia(Fast Track)
Phase IIwww.glenveigh.com
Edarbi®azilsartan medoxomil
Takeda PharmaceuticalsDeerfield, IL
hypertension (pediatric) Phase Iwww.takeda.com
GSK2944406(amlodipine/losartan fixed-dose combination)
GlaxoSmithKlineRsch. Triangle Park, NC
hypertension Phase Iwww.gsk.com
HL-040XC(atorvastatin/losartan fixed-dose combination)
HanAll BiopharmaSeoul, South Korea
hypertension(see also lipid disorders)
Phase IIwww.hanall.co.kr
HT-101(amiloride/spironolactone)
Hemodynamic TherapeuticsDurham, NC
obesity-related resistant hypertension
Phase IIwww.hemodynamictx.com
KD027(PDE5 inhibitor)
Kadmon PharmaceuticalsWarrendale, PA
hypertension Phase Iwww.kadmon.com
LCZ696(ARB/NEP inhibitor)
Novartis PharmaceuticalsEast Hanover, NJ
essential hypertension(see also heart failure)
Phase IIwww.novartis.com
MK-7145 MerckWhitehouse Station, NJ
hypertension Phase I completedwww.merck.com
MK-8150 MerckWhitehouse Station, NJ
hypertension Phase Iwww.merck.com
nebivolol/valsartanfixed-dose combination
Forest LaboratoriesNew York, NY
essential hypertension Phase IIIwww.frx.com
PB1046(Vasomera)
PhaseBio PharmaceuticalsMalvern, PA
essential hypertension Phase I/IIwww.phasebio.com
perindopril/amlodipine fixed-dose combination
XOMABerkeley, CA
hypertension Phase IIIwww.xoma.com
PL-3994(natriuretic-peptide)
Palatin TechnologiesCranbury, NJ
hypertension(see also heart failure)
Phase IIwww.palatin.com
Tekturna®
aliskirenNovartis PharmaceuticalsEast Hanover, NJ
hypertension in children age 6-17 years of age(see also atherosclerosis, heart failure)
Phase IIIwww.novartis.com
Hypertension (High Blood Pressure)
Product Name Sponsor Indication Development Phase
Medicines in Development heart disease and stroke 2013 11
medicines in development for heart disease and stroke
99m-Tc-EC-G CellPointCentennial, CO
myocardial ischemia (diagnosis) Phase IIwww.cellpointweb.com
Amiscan™Tc-99m-glucarate
Molecular Targeting TechnologiesWest Chester, PA
acute coronary syndrome (diagnosis)
Phase IIwww.mtarget.com
BFPET™(myocardial perfusion imaging agent)
FluoroPharmaMontclair, NJ
coronary artery disease (diagnosis) Phase Iwww.fluoropharma.com
CardioPET™cardiac PET imaging agent
FluoroPharmaMontclair, NJ
coronary artery disease (diagnosis) Phase IIwww.fluoropharma.com
fluorine-18-ML-10 IBA Molecular USDulles, VA
stroke (diagnosis) Phase IIwww.iba-molecular.com
flurpiridaz F-18 Lantheus Medical ImagingN. Billerica, MA
coronary artery disease (diagnosis) Phase IIIwww.lantheus.com
Imagify™perflubutane
AcusphereLexington, MA
coronary artery disease (diagnosis) Phase IIIwww.acusphere.com
LMI 1195(PET imaging agent)
Lantheus Medical ImagingN. Billerica, MA
heart failure (diagnosis) Phase Iwww.lantheus.com
ThromboView®
Tc-99m 3B6/22 anti-fibrin mAbAGEN Biomedical(Agenix)Victoria, Australia
deep vein thrombosis (diagnosis),pulmonary thrombosis (diagnosis)
Phase IIwww.agenix.com
Ischemic Disorders
Product Name Sponsor Indication Development Phase
ACY001(autologous AC133+ selected adult bone marrow-derived stem cell therapy)
Compass BiomedicalCleveland, OH
chronic coronary ischemia Phase Iwww.compassbiomedical.com
adipose-derived regenerative cell (ADRC) therapy
Cytori TherapeuticsSan Diego, CA
chronic myocardial ischemia (see also heart attack)
Phase I/IIwww.cytori.com
Imaging Agents
Product Name Sponsor Indication Development Phase
Medicines in Development heart disease and stroke 201312
medicines in development for heart disease and stroke
Ischemic Disorders
Product Name Sponsor Indication Development Phase
ALD-201(bone marrow-derived adult stem cell therapy)
CytomedixGaithersburg, MD
ischemic heart failure Phase Iwww.cytomedix.com
ALD-301(bone marrow-derived adult stem cell therapy)
CytomedixGaithersburg, MD
critical limb ischemia Phase I/IIwww.cytomedix.com
ALO212(stem cell therapy)
Compass BiomedicalCleveland, OH
critical limb ischemia Phase Iwww.compassbiomedical.com
allogeneic/autologous adult mesenchymal stem cell therapy
BioCardiaSan Carlos, CA
ischemic heart disorder Phase I/IIwww.biocardia.com
autologous stem cell therapy Baxter HealthcareDeerfield, IL
myocardial ischemia Phase IIIwww.baxter.com
Bendavia™mitochondrial-targetingshort peptide
Stealth PeptidesNewtown Centre, MA
ischemic reperfusion in acute myocardial infarction and heart failure
Phase IIwww.stealthpeptides.com
Collategene®
beperminogene perplasmid (HGF plasmid)
AnGesBethesda, MDMitsubishi Tanabe Pharma AmericaJersey City, NJ------------------------------------------------AnGesBethesda, MD
critical limb ischemia(Fast Track)
--------------------------------------ischemic heart disorder
Phase IIIwww.anges-mg.comwww.mt-pharma-america.com
-----------------------------------------Phase Iwww.anges-mg.com
ERC-124(endometrial blood stem cell therapy)
MediStemSan Diego, CA
critical limb ischemia in clinical trialswww.medisteminc.com
Generx®alferminogene tadenovec(Ad5FGF-4)
Cardium TherapeuticsSan Diego, CA
myocardial ischemia(Fast Track)
Phase IIIwww.cardiumthx.com
GS-6615(sodium channel antagonist)
Gilead SciencesFoster City, CA
ischemic heart disease(see also arrhythmia)
Phase Iwww.gilead.com
JVS-100(stromal cell-derived factor-1)
Juventas TherapeuticsCleveland, OH
critical limb ischemia(see also heart failure)
Phase IIwww.juventasinc.com
MESENDO combination autologous stem cell therapy
TCA Cellular TherapyCovington, LA
coronary ischemia, lower limb ischemia
Phase IIwww.tcacellulartherapy.com
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Ischemic Disorders
Product Name Sponsor Indication Development Phase
MP4OX SangartSan Diego, CA
ischemia Phase II completedwww.sangart.com
PLX-PAD(stem cell therapy)
Pluristem TherapeuticsHaifa, Israel
critical limb ischemia (see also peripheral vascular disease)
Phase Iwww.pluristem.com
VM202(modified hepatocyte growthfactor gene therapy)
ViroMedSeoul, South Korea
myocardial ischemia(see also peripheral vascular disease)
Phase Iwww.viromed.co.kr
Lipid Disorders
Product Name Sponsor Indication Development Phase
ALN-PCS(PCSK9 protein inhibitor)
Alnylam PharmaceuticalsCambridge, MAThe Medicines CompanyParsippany, NJ
hypercholesterolemia Phase Iwww.alnylam.comwww.themedicinescompany.com
AMG 145(PCSK9 inhibitor mAb)
AmgenThousand Oaks, CA
heterozygous familial hypercholesterolemia, hypercholesterolemia
Phase Iwww.amgen.com
AMR-102(icosapent ethyl/statin fixed-dose combination)
AmarinBedminster, NJ
hyperlipidemia Phase Iwww.amarincorp.com
anacetrapib(MK-0859)
MerckWhitehouse Station, NJ
heterozygous familial hypercholesterolemia, hypercholesterolemia(see also atherosclerosis)
Phase IIIwww.merck.com
ARI-3037MO(niacin analog)
Arisaph PharmaceuticalsBoston, MA
dyslipidemia Phase Iwww.arisaph.com
CAT-2003(eicosapentaenoic acid/niacin)
Catabasis PharmaceuticalsCambridge, MA
severe hypertriglyceridemia Phase Iwww.catabasis.com
Medicines in Development heart disease and stroke 201314
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Lipid Disorders
Product Name Sponsor Indication Development Phase
CER-001(recombinant HDL)
Cerenis TherapeuticsAnn Arbor, MI
homozygous familial hypercholesterolemia(see also acute coronary syndrome)
Phase IIwww.cerenis.com
CER-002(PPAR-delta agonist)
Cerenis TherapeuticsAnn Arbor, MI
dyslipidemia with low HDL Phase Iwww.cerenis.com
CER-627(low flushing niacin)
Cerenis TherapeuticsAnn Arbor, MI
dyslipidemia with low HDL Phase Iwww.cerenis.com
diazoxide cholinecontrolled-release
EssentialisCarlsbad, CA
hypertriglyceridemia Phase IIwww.essentialistherapeutics.com
Epanova™eicosapentaenoic acid/docosahexaenoic acid
Omthera PharmaceuticalsPrinceton, NJ
hypertriglyceridemia(combination therapy)--------------------------------------hypertriglyceridemia(monotherapy)
Phase IIIwww.omthera.com-----------------------------------------Phase II/IIIwww.omthera.com
ETC-1002(ATP citrate [pro-S]-lyase inhibitor/adenylate kinase stimulator)
Esperion TherapeuticsPlymouth, MI
dyslipidemia Phase IIwww.esperion.com
fenofibrate/simvastatinfixed-dose combination
AbbVieNorth Chicago, IL
hyperlipidemia Phase IIIwww.abbvie.com
GSK1292263(bombesin receptor agonist)
GlaxoSmithKlineRsch. Triangle Park, NC
hyperlipidemia Phase II completedwww.gsk.com
HL-040XC(atorvastatin/losartan fixed-dose combination)
HanAll BiopharmaSeoul, South Korea
hyperlipidemia(see also hypertension)
Phase IIwww.hanall.co.kr
HPP593(PPAR-delta agonist)
High Point PharmaceuticalsHigh Point, NC
dyslipidemia Phase Iwww.highpointpharma.com
ISIS-APOCIIIRx(apolipoprotein C-III inhibitor)
Isis PharmaceuticalsCarlsbad, CA
hypertriglyceridemia Phase Iwww.isispharm.com
K-877(PPAR-alpha agonist)
Kowa Pharmaceuticals AmericaMontgomery, AL
dyslipidemia Phase Iwww.kowa.co.jp
KD026(MTP inhibitor)
Kadmon PharmaceuticalsWarrendale, PA
dyslipidemia Phase IIwww.kadmon.com
Kynamro®
mipomersenGenzymeCambridge, MA
severe homozygous familial hypercholesterolemia
Phase IIIwww.genzyme.com
Medicines in Development heart disease and stroke 2013 15
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Lipid Disorders
Product Name Sponsor Indication Development Phase
MBX-8025(PPAR-delta agonist)
MetabolexHayward, CA
dyslipidemia Phase IIwww.metabolex.com
MGL-3196(liver-directed thyroid hormone receptor-ß agonist)
Madrigal PharmaceuticalsFort Washington, PA
dyslipidemia, hypercholesterolemia
Phase Iwww.madrigalpharma.com
pradigastat(LCQ908)
Novartis PharmaceuticalsEast Hanover, NJ
familial chylomicronemia syndrome(see also coronary artery disease)--------------------------------------hypertriglyceridemia
Phase IIIwww.novartis.com
-----------------------------------------Phase IIwww.novartis.com
RN316 (PF-04950615)
PfizerNew York, NY
hypercholesterolemia Phase IIwww.pfizer.com
RN317 (PF-05335810)
PfizerNew York, NY
hypercholesterolemia Phase Iwww.pfizer.com
SAR236553(anti-PCSK-9 mAb)
Regeneron PharmaceuticalsTarrytown, NYSanofi USBridgewater, NJ
heterozygous familial hypercholesterolemia,hypercholesterolemia
Phase IIIwww.regeneron.comwww.sanofi.com
SCH-900271 MerckWhitehouse Station, NJ
hyperlipidemia Phase II completedwww.merck.com
TAP311 Novartis PharmaceuticalsEast Hanover, NJ
dyslipidemia Phase I completedwww.novartis.com
XZK-monascus(HMG-CoA reductase inhibitor)
Beijing Peking University WBL BiotechBeijing, China
hyperlipidemia Phase II
Peripheral Vascular Disease
Product Name Sponsor Indication Development Phase
Benlysta®
belimumabGlaxoSmithKlineRsch. Triangle Park, NC
vasculitis Phase IIIwww.gsk.com
Brilinta®
ticagrelorAstraZenecaWilmington, DE
peripheral arterial disease(see also heart attack)
Phase IIIwww.astrazeneca.com
Medicines in Development heart disease and stroke 201316
medicines in development for heart disease and stroke
Peripheral Vascular Disease
Product Name Sponsor Indication Development Phase
defibrotide GentiumVilla Guardia, ItalySigma-Tau PharmaceuticalsGaithersburg, MD
treatment of hepatic venous occlusive disease after stem cell transplantation
Phase IIIwww.gentium.comwww.sigmatau.com
human plasma-derived fibrinolysin GrifolsBarcelona, Spain
peripheral vascular occlusive disease
Phase Iwww.grifols.com
inclacumab RocheNutley, NJ
prevention of saphenous vein graft disease(see also acute coronary syndrome, heart attack)
Phase IIwww.roche.com
K-134(PDE3 inhibitor)
Kowa Pharmaceuticals AmericaMontgomery, AL
arteriosclerosis obliterans Phase IIwww.kowa.co.jp
MABp1(IL-1α mAb)
XBiotechAustin, TX
vascular restenosis(Fast Track)
Phase IIwww.xbiotech.com
MultiGeneAngioperipheral arterial disease cell therapy
MultiGene Vascular SystemsNesher, Israel
peripheral arterial disease Phase I/IIwww.mgvs.co.il
paclitaxel coated balloon LutonixMinneapolis, MN
peripheral arterial disease Phase IIwww.lutonix.com
paclitaxel-eluting balloon catheter MEDRAD(Bayer HealthCare)Warrendale, PA
stenotic peripheral artery lesions application submittedwww.medrad.com
PLX-PAD(stem cell therapy)
Pluristem TherapeuticsHaifa, Israel
intermittent claudication(see also ischemic disorders)
Phase IIwww.pluristem.com
PRT-201 Proteon TherapeuticsWaltham, MA
peripheral arterial disease(see also adjunctive therapies)
Phase Iwww.proteontherapeutics.com
TSC(trans-sodium crocetinate)
Diffusion PharmaceuticalsCharlottesville, VA
peripheral arterial disease Phase II completedwww.diffusionpharma.com
TV1001(sodium nitrite oral)
TheravascCleveland, OH
peripheral arterial disease Phase IIwww.theravasc.com
VM202(modified hepatocyte growth factor gene therapy)
ViroMedSeoul, South Korea
peripheral arterial disease(see also ischemic disorders)
Phase IIwww.viromed.co.kr
Medicines in Development heart disease and stroke 2013 17
medicines in development for heart disease and stroke
Pulmonary Vascular Disease
Product Name Sponsor Indication Development Phase
Adcirca™tadalafil
Eli LillyIndianapolis, IN
pulmonary hypertension (pediatric)
Phase I/IIwww.lilly.com
APD811(prostanoid receptor agonist)
Arena PharmaceuticalsSan Diego, CA
pulmonary arterial hypertension Phase Iwww.arenapharm.com
beraprost 314d(single isomer version)
United TherapeuticsSilver Spring, MD
pulmonary arterial hypertension Phase IIwww.unither.com
DA-8159(PDE5 inhibitor)
Dong-A PharmaceuticalSeoul, South Korea
pulmonary arterial hypertension Phase IIen.donga.co.kr
INOmax®
nitric oxide inhalation(Orphan Drug)
IkariaHampton, NJ
pulmonary arterial hypertension Phase Iwww.ikaria.com
Letairis®
ambrisentan(Orphan Drug)
Gilead SciencesFoster City, CA
pulmonary hypertension (pediatric)
Phase IIwww.gilead.com
macitentan(endothelin A receptor antagonist)(Orphan Drug)
Actelion PharmaceuticalsSouth San Francisco, CA
pulmonary arterial hypertension application submittedwww.actelion.com
nitric oxide inhalation GeNOWaltham, MA
pulmonary arterial hypertension Phase II www.genollc.com
nitrite inhalation(Orphan Drug)
Aires PharmaceuticalsSan Diego, CA
pulmonary arterial hypertension Phase IIwww.airespharma.com
riociguat Bayer HealthCare PharmaceuticalsWayne, NJ
chronic thromboembolic pulmonary hypertension
application submittedwww.bayerpharma.com
SAR407899(Rho kinase inhibitor)
Sanofi USBridgewater, NJ
pulmonary hypertension Phase Iwww.sanofi.com
selexipag Actelion PharmaceuticalsSouth San Francisco, CA
pulmonary arterial hypertension Phase IIIwww.actelion.com
Tracleer®
bosentanActelion PharmaceuticalsSouth San Francisco, CA
pulmonary arterial hypertension(pediatric)
Phase IIIwww.actelion.com
treprostinil (oral)(sustained-release)
United TherapeuticsSilver Spring, MD
pulmonary arterial hypertension application submittedwww.unither.com
Medicines in Development heart disease and stroke 201318
medicines in development for heart disease and stroke
Stroke
Product Name Sponsor Indication Development Phase
3K3A-APC(recombinant human activated protein C)
ZZ BiotechHouston, TX
stroke Phase Iwww.zzbiotech.com
ALD-401(bone marrow-derived adult stem cell therapy)
CytomedixGaithersburg, MD
stroke Phase IIwww.cytomedix.com
allogeneic mesenchymal bone marrow cell therapy
Stemedica Cell TechnologiesSan Diego, CA
ischemic stroke Phase I/IIwww.stemedica.com
Ampyra™fampridine sustained-release
Acorda TherapeuticsArdsley, NY
post-stroke deficits Phase IIwww.acorda.com
betrixaban Portola PharmaceuticalsSouth San Francisco, CA
stroke (prevention) in patientswith atrial fibrillation(see also thrombosis)
Phase IIwww.portola.com
CNTO-0007(cell therapy)
Janssen Research & DevelopmentRaritan, NJ
ischemic stroke Phase Iwww.janssenrnd.com
desmoteplase LundbeckDeerfield, IL
ischemic stroke(Fast Track)
Phase IIIwww.lundbeck.com
GM602(nervous system modulator)
Genervon BiopharmaceuticalsPasadena, CA
acute ischemic stroke Phase IIwww.genervon.com
GSK249320(myelin-associated glycoprotein mAb)
GlaxoSmithKlineRsch. Triangle Park, NC
stroke Phase IIwww.gsk.com
metamfetamine Sinapis PharmaJacksonville, FL
stroke Phase I completedwww.sinapispharma.com
MP-124(PARP inhibitor)
Mitsubishi Tanabe Pharma AmericaJersey City, NJ
acute ischemic stroke Phase Iwww.mt-pharma.co.jp
MultiStem®
stem cell therapyAthersysCleveland, OH
stroke(see also heart attack)
Phase IIwww.athersys.com
NA-1(signal transduction pathway inhibitor)
NoNO IncToronto, Canada
acute ischemic stroke Phase II completedwww.nonoinc.ca
NEU 2000 GNT PharmaYongin, South Korea
stroke(see also heart attack)
Phase I completedwww.gntpharma.com
Medicines in Development heart disease and stroke 2013 19
medicines in development for heart disease and stroke
Stroke
Product Name Sponsor Indication Development Phase
PF-03049423 PfizerNew York, NY
ischemic stroke Phase IIwww.pfizer.com
RP-1127(NCCA-ATP channel inhibitor)
Remedy PharmaceuticalsNew York, NY
stroke Phase IIwww.remedypharmaceuticals.com
SAR126119(TAFIa inhibitor)
Sanofi USBridgewater, NJ
acute ischemic stroke Phase Iwww.sanofi.com
SB623(stem cell therapy)
SanBioMountain View, CA
stroke Phase I/IIwww.san-bio.com
TS01(recombinant complementC1-inactivator-protein)
Thrombolytic Science InternationalCambridge, MA
stroke Phase Iwww.tsillc.net
Thrombosis
Product Name Sponsor Indication Development Phase
betrixaban Portola PharmaceuticalsSouth San Francisco, CA
thromboembolism (prevention)(see also stroke)
Phase IIIwww.portola.com
cangrelor The Medicines CompanyParsippany, NJ
prevention of coronary thrombosisprior to coronary artery bypass graft (CABG)(see also acute coronary syndrome, coronary artery disease)
Phase IIwww.themedicinescompany.com
clopidogrel intravenous(MDCO-157)
The Medicines CompanyParsippany, NJ
coronary thrombosis (prevention) Phase IIIwww.themedicinescompany.com
desirudin IV(intravenous)
Canyon PharmaceuticalsColumbia, MD
intravenous bolus-only administration in patients undergoing coronary artery stenting
in clinical trialswww.canyonpharma.com
edoxaban(oral factor Xa inhibitor)
Daiichi SankyoParsippany, NJ
venous thromboembolism (prevention), embolism/stroke in patients with atrial fibrillation (prevention)
Phase IIIwww.daiichisankyo.com
Medicines in Development Heart Disease and Stroke 201320
Medicines in Development for Heart Disease and Stroke
Eliquis®
apixabanBristol-Myers SquibbPrinceton, NJPfizerNew York, NY
prevention of venous thromboembolism, treatment of venous thrombosis
Phase IIIwww.bms.comwww.pfizer.com
GCC-4401 Green CrossYongin, South Korea
coronary thrombosis Phase I completedwww.greencross.co.kr
Iprivask®
desirudin SC(subcutaneous)
Canyon PharmaceuticalsColumbia, MD
thromboembolism in patients with suspected heparin-induced thrombocytopenia (prevention and treatment), venous thromboembolism in high-risk surgical and medical patients (prevention)
in clinical trialswww.canyonpharma.com
ISIS-FXIRx(factor XI inhibitor)
Isis PharmaceuticalsCarlsbad, CA
venous thromboembolism Phase Iwww.isispharm.com
Pradaxa®
dabigatran etexilateBoehringer Ingelheim PharmaceuticalsRidgefield, CT
acute treatment and reduction in the risk of recurrence of deep venous thrombosis and pulmonary embolism
Phase IIIwww.boehringer-ingelheim.com
REG2(pegnivacogin subcutaneous)
Regado BiosciencesBasking Ridge, NJ
venous thrombosis Phase Iwww.regadobio.com
vorapaxar(thrombin/PAR-1 receptorantagonist)
MerckWhitehouse Station, NJ
arterial thrombosis (prevention)(Fast Track)(see also acute coronary syndrome)
Phase IIIwww.merck.com
Xarelto®
rivaroxabanBayer HealthCare PharmaceuticalsWayne, NJJanssen Research & DevelopmentRaritan, NJ
venous thromboembolism (pediatric)(see also acute coronary syndrome, other)
Phase Iwww.bayerpharma.comwww.janssenrnd.com
Other
Product Name Sponsor Indication Development Phase
ACZ885(canakinumab)
Novartis PharmaceuticalsEast Hanover, NJ
secondary prevention of cardiovascular events(see also atherosclerosis)
Phase IIIwww.novartis.com
Thrombosis
Product Name Sponsor Indication Development Phase
Medicines in Development heart disease and stroke 2013 21
medicines in development for heart disease and stroke
aleglitazar(PPAR alpha/gamma co-agonist)
RocheNutley, NJ
prevention of cardiovascular disorders in patients with type 2 diabetes
Phase IIIwww.roche.com
ALN-TTRsc(prealbumin inhibitor)
Alnylam PharmaceuticalsCambridge, MA
familial amyloidotic cardiomyopathy
Phase Iwww.alnylam.com
Bydureon®
exenatide extended-release for injectable suspension
AstraZenecaWilmington, DEBristol-Myers SquibbPrinceton, NJ
cardiovascular outcomes Phase IIIwww.astrazeneca.comwww.bms.com
caplacizumab(Orphan Drug)
AblynxGhent, Belguim
thrombotic thrombocytopenic purpura
Phase IIwww.ablynx.com
CardiaPill®aspirin/lisinopril/lovastatin
CardioPharmaWilmington, NC
cardiovascular disorders in clinical trialswww.cardio-pharma.com
cardiovascular disease medicine Eli LillyIndianapolis, IN
cardiovascular disease Phase Iwww.lilly.com
droxidopa(Orphan Drug)
Chelsea TherapeuticsCharlotte, NC
orthostatic hypotension(Fast Track)
application submittedwww.chelseatherapeutics.com
evacetrapib Eli LillyIndianapolis, IN
prevention of cardiovascular events in high-risk vascular disease
Phase IIIwww.lilly.com
Forxiga®
dapagliflozinAstraZenecaWilmington, DEBristol-Myers SquibbPrinceton, NJ
cardiovascular outcomes Phase IIIwww.astrazeneca.comwww.bms.com
ixmyelocel-T(stem cell therapy)
Aastrom BiosciencesAnn Arbor, MI
dilated cardiomyopathy Phase IIwww.aastrom.com
MEK162(MEK inhibitor)
Novartis PharmaceuticalsEast Hanover, NJ
Noonan syndrome hypertrophiccardiomyopathy
Phase IIwww.novartis.com
Onglyza®
saxagliptinAstraZenecaWilmington, DEBristol-Myers SquibbPrinceton, NJ
cardiovascular outcomes Phase IIIwww.astrazeneca.comwww.bms.com
PA8140(aspirin 81mg/omeprazole 40mg)
POZENChapel Hill, NC
secondary prevention of cardiovascular and cerebrovascular disease in patients at risk for aspirin-induced ulcers
application submittedwww.pozen.com
Other
Product Name Sponsor Indication Development Phase
Medicines in Development Heart Disease and Stroke 201322
PA32540(aspirin 325mg/omeprazole 40mg)
POZENChapel Hill, NC
secondary prevention of cardiovascular and cerebrovascular disease in patients at risk for aspirin-induced ulcers
application submittedwww.pozen.com
RX-10001(lipid modulator)
Resolvyx PharmaceuticalsCambridge, MA
cardiovascular disorders Phase I completedwww.resolvyx.com
T89(herbal medicine product)
Tasly PharmaceuticalsRockville, MD
angina pectoris Phase IIIwww.tasly.com
Vascana™nitroglycerin topical
MediQuest TherapeuticsMaple Valley, WA
Raynaud’s disease Phase IIIwww.mqti.com
Vyndaqel®tafamidis meglumine
PfizerNew York, NY
transthyretin familial amyloid cardiomyopathy
Phase IIIwww.pfizer.com
Xarelto®
rivaroxabanBayer HealthCare PharmaceuticalsWayne, NJJanssen Research & DevelopmentRaritan, NJ
prevention of cardiovascular events secondary to chronic heart failure, coronary or peripheral artery disease, or atrial fibrillation(Fast Track)(see also acute coronary syndrome, thrombosis)
Phase IIIwww.bayerpharma.comwww.janssenrnd.com
Medicines in Development for Heart Disease and Stroke
Other
Product Name Sponsor Indication Development Phase
The 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 being developed by U.S. based companies conducting trials in the United States and abroad, PhRMA-member companies conducting trials in the United States and abroad, and foreign companies conducting clinical trials in the United States. The information in this report may not be comprehensive. For more specific information about a particular product, contact the individual company directly 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) 835-3460
www.phrma.org | www.innovation.org | www.pparx.org
Provided 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 proper credit is given.
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Medicines in Development heart disease and stroke 2013 23
Glossary
adjunctive therapy—Auxiliary treatment that is secondary to the main treatment.
angina pectoris—Chest pain, usually caused by “myocardial ischemia,” a low supply of oxygen to the heart muscle resulting from hardening, narrowing, and sometimes spasm of the coronary arteries.
application submitted—An application for marketing has been submitted by the company to the Food and Drug Admin-istration (FDA).
arrhythmia—Abnormal heart rhythm, usually detected by an electrocardio-gram. Arrhythmias can be caused by several factors, such as coronary artery disease, heart valve problems or hyper-thyroidism.
arteriosclerosis obliterans—An alter-native term for peripheral vascular disease.
atherosclerosis—A common disease in which deposits of plaque containing calcium and fatty substances, such as cholesterol, are formed within the inner layers of the arteries. It is a condition that progresses over decades, chiefly affecting the arteries of the heart, brain and extremities. Its complications include heart attacks and strokes.
atrial fibrillation—Very fast electrical discharge patterns that make the heart’s atria contract extremely rapidly, which causes the ventricles to contract faster and less efficiently than normal. As a result, inadequate amounts of blood are pumped out of the heart, blood pressure falls, and heart failure may occur.
bypass graft—A vein or artery graft that bypasses blockage in an artery.
cardiomyopathy—A type of heart disease in which the heart muscle is abnormally enlarged, thickened and/or stiffened. As a result, the heart muscle’s ability to pump blood is usually impaired.
cardiovascular—Of or relating to the heart and blood vessels.
coronary artery disease—A condition caused by atherosclerosis of the arteries that supply the heart.
critical limb ischemia (Cli)—CLI is a severe obstruction of the arteries that seriously decreases blood flow to the extremities (arms, hands, legs, feet) and has progressed to the point of severe pain and even skin ulcers or sores. The pain, called “rest pain,” caused by CLI can wake up a person at night. CLI is a very severe condition of peripheral arterial disease and needs comprehen-sive treatment by a vascular surgeon or specialist.
deep vein thrombosis—Blood clotting within the deep-lying veins, often in the legs or pelvic veins.
dyslipidemia—A condition marked by abnormal concentrations of lipids or lipoproteins in the blood.
embolism—The obstruction of a blood vessel by a foreign substance or a blood clot. Foreign substances that can cause embolism include an air bubble, amni-otic fluid, a globule of fat, a clump of bacteria, chemicals, and drugs. Blood clots are the most common cause of embolism. The term “embolus” refers to the substance or clot that is obstructing the blood vessel, while “embolism” refers to the process by which that happens.
Fast Track—A process designed to facilitate the development and expedite the review of drugs to treat serious diseases and fill an unmet medical need. The status is assigned by the U.S. Food and Drug Administration. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious diseases. Gener-ally, determining factors include whether the drug will have an impact on such factors as survival, day-to-day function-ing, or the likelihood that the disease, if left untreated, will progress from a less severe condition to a more serious one. Filling an unmet medical need is defined as providing a therapy where none exists or providing a therapy which may be
potentially superior to existing therapy. Once a drug receives Fast Track designa-tion, early and frequent communication between the FDA and a drug company is encouraged throughout the entire drug development and review process. The frequency of communication assures that questions and issues are resolved quickly, often leading to earlier drug approval and access by patients.
genotype—The genetic constitution (genome) of a cell, an individual, or an organism. The genotype of a person is her or his genetic makeup. It can pertain to all genes or to a specific gene.
HDl—High-density lipoprotein, some-times called “good cholesterol.”
heart attack (myocardial infarction)—A part of the heart muscle (myocardium) dies as a result of blood and oxygen deprivation.
heart failure—The end result of many different types of heart disease. The heart cannot pump blood out normally. This results in congestion (water and salt retention) in the lungs, swelling in the extremities, and reduced blood flow to body tissues.
hemodialysis—A medical procedure that uses a special machine (a dialysis ma-chine) to filter waste products from the blood and to restore normal constituents to it.
hypercholesterolemia—The presence of an abnormally large amount of cho-lesterol in the cells and plasma of the circulating blood.
hyperlipidemia—A group of metabolic disorders characterized by high levels of lipids (fatty substances, including choles-terol) in the blood. Hyperlipidemia is a risk factor for accelerated atherosclerosis and premature heart attacks.
hypertension (high blood pressure)—Persistent elevation of blood pressure above the normal range while the heart is in systolic (contracting) or diastolic (relaxed) mode. Uncontrolled, chronic
Medicines in Development heart disease and stroke 201324
Glossary
hypertension strains the heart, damages arteries and creates a greater risk of heart attack, stroke and kidney problems.
hypertriglyceridemia—An elevated triglyceride concentration in the blood.
hypotension—A sudden fall in blood pressure. It may be caused by hypovo-lemia resulting from the excessive use of diuretics, vasodilators, or other types of drugs, dehydration, or prolonged bed rest. The disorder may be associated with Addison’s disease, atherosclerosis (build-up of fatty deposits in the arter-ies), diabetes, and certain neurological disorders. Symptoms, which generally occur after sudden standing, include diz-ziness, light-headedness, blurred vision, and the temporary loss of consciousness.
imaging agent—A substance used to enhance images of organs and spaces in the body.
intermittent claudication—The most prominent symptom of peripheral arte-rial disease (PAD). It occurs in one-third to one-half of PAD patients. Claudica-tion refers to the pain that occurs in PAD patients when they exercise, particularly during walking, which is relieved only by rest. Leg pain occurs in one leg in 40 percent of patients and in both legs in 60 percent of patients.
ischemia—Insufficient supply of blood to an organ or tissue, which can cause or-gan damage such as an ischemic stroke.
lipids—A group of fatty substances that includes triglycerides (the principal forms of fat in body fat), phospholipids (im-portant constituents of cell membranes), and sterols (such as cholesterol).
peripheral vascular disease—The obstruction of blood supply to the ex-tremities, particularly the legs, caused by atherosclerosis.
peT imaging—Positron emission tomog-raphy.
phase i—Safety testing and pharmaco-logical profiling in humans.
phase ii—Effectiveness testing in humans.
phase iii—Extensive clinical trials in humans.
preeclampsia—A condition in pregnant women characterized by high blood pressure and high levels of protein in urine.
pulmonary hypertension—High blood pressure in the arteries supplying the lungs due to increased resistance to blood flow through the lungs.
Raynaud’s disease—A circulatory disor-der caused by insufficient blood supply to the hands and feet, resulting in cya-nosis, numbness, pain, and, in extreme cases, gangrene.
reperfusion injury—Refers to myocar-dial, vascular, or electro-physiological dysfunction that is induced by the restoration of blood flow to previously ischemic tissue.
restenosis—A condition where an artery plugs up again following treatment to open it up.
stent—A metal device that is used to hold tissue in place. For example, a stent can keep blood vessels open after a sur-gical procedure or heart catheterization.
stroke—Usually caused by atheroscle-rosis. It results in death or serious brain damage, such as paralysis or loss of speech. An ischemic stroke is caused by blocked or narrowed arteries that prevent sufficient blood and oxygen from reaching the brain.
thromboembolism—Blockage of a blood vessel by a fragment that has broken off and been carried from a thrombus (blood clot) elsewhere in the circulation.
thrombosis—The formation of a blood clot within the heart or a blood vessel.
the drug discovery, development and approval process
The U.S. system of new drug approvals is perhaps 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 of Drug Development. Only five in 5,000 com-pounds that enter preclinical testing make it to human testing. And only one of those five is approved for sale.
On average, it costs a company $1.2 billion, including the cost of failures, to get one new medicine from the laboratory to U.S. patients, according to a recent study by the Tufts Center for the Study of Drug Development.
Once a new compound has been identified in the laboratory, medicines are usually developed as follows:
Preclinical Testing. A pharmaceutical company conducts laboratory and animal studies to show biological activity of the compound against the targeted 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 Drug Administration (FDA) to begin to test the drug
in people. The IND shows results of previous experiments; how, where and by whom the new studies will be conducted; the chemical structure of the compound; how it is thought to work in the body; any toxic effects found in the animal studies; 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. Progress reports on clinical trials must be submitted at least annually to FDA and the IRB.
Clinical Trials, Phase I—Researchers test the drug in a small group of people, usually between 20 and 80 healthy adult volunteers, to evaluate its initial safety and tolerability profile, deter-mine a safe dosage range, and identify potential side effects.
Clinical Trials, Phase II—The drug is given to volunteer patients, usually between 100 and 300, to see if it is effective, identify an optimal dose, and to further evaluate its short-term safety.
Clinical Trials, Phase III—The drug is given to a larger, more diverse patient population, often involving between 1,000 and 3,000 patients (but sometime many more thousands), to gener-
ate statistically significant evidence to confirm its safety and effectiveness. They are the lon-gest studies, and usually take place in multiple sites around the world.
New Drug Application (NDA)/Biologic License Application (BLA). Following the completion of all three phases of clinical trials, a company analyzes all of the data and files an NDA or BLA with FDA if the data successfully demonstrate both safety and effectiveness. The applications contain all of the scientific information that the company has gathered. Applications typically run 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 continue to submit periodic reports to FDA, including any cases of adverse reactions and appropriate quality-control records. For some medicines, FDA requires additional trials (Phase IV) to evaluate long-term effects.
Discovering and developing safe and effective new medicines is a long, difficult, and expensive process. PhRMA member companies invested an estimated $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 process
PRE-
DIS
COV
ERY
DRUG DISCOVERY PRECLINICAL CLINICAL TRIALS FDA REVIEW LG-SCALE MFG
3 – 6 Y E A RS 6 – 7 Y E A RS 0. 5 – 2 Y E A RS
100 – 300 1,000 – 3,00020 –80
PHASE 2
PHASE 3
PHASE 1
IND
SU
BM
ITTE
D
ND
A S
UB
MIT
TED
PHA
SE 4
: PO
ST-M
AR
KET
ING
SU
RVEI
LLA
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NUMBER OF VOLUNTEERS
ONE FDA-APPROVED
DRUG
5,000 – 10,000
COMPOUNDS
250 5
Drug Discovery and Development: A LONG, RISKY ROAD