PhRMA Report 2012: Medicines in Development for Diabetes

America’s biopharmaceutical research com-panies are developing 221 medicines to treat diabetes and related conditions. All of the medicines in this report are either in clinical trials or awaiting approval by the U.S. Food and Drug Administration. Diabetes affects nearly 26 million Americans —8.3 percent of the U.S. population—and about one-quarter are unaware they have the disease. Unfortunately, while the death rate due to diabetes is declining, the rate of new cases has been rising. The number of Americans diagnosed with diabetes has more than tripled since 1980, according to the U.S. Centers for Disease Control and Prevention (CDC). Lifestyle choices can affect this increase. The CDC-led National Diabetes Prevention Program found that weight loss and increased physical activity in people at high risk for diabetes reduced the development of type 2 diabetes by 58 percent in a 3-year period. Medicines can also help reduce the risk of type 2 diabetes. For example, one medicine was found in studies to lower the risk by 31 percent.According to the American Diabetes Asso-ciation, most Americans with diabetes have

type 2, in which relative insulin deficiency combines with the body failing to properly use insulin. Between 5 percent and 10 percent of Americans with diabetes have type 1, in which the body fails to produce insulin.The medicines in the pipeline today offer hope of reducing the human toll and eco-nomic costs of diabetes. Examples of some medicines now being tested include: • A medicine that improves

glucose-dependent insulin secretion. • A medicine designed to inhibit an enzyme

linked to diabetic neuropathy. • A medicine to treat type 2 diabetes that

may allow for once-weekly dosing.While diabetes remains a formidable foe, America’s biopharmaceutical research com-panies are continuing their efforts to develop novel and more effective therapies to treat the disease and increase patients’ quality of life.

Biopharmaceutical Research Companies Are Developing More Than 220 Medicines to Treat Diabetes and Related Conditions

Medicines in Development

Diabetespresented by america’s biopharmaceutical research companies

2012 RepoRt

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14

Medicines in Development

For Diabetes*

* Some medicines are listed in more than one category

79 million American

adults have

prediabetes

18.8 million Americans have been diagnosed

with diabetes

Each day more than

5,000 American adults are diagnosed

with diabetes

7million Americans

areundiagnosed

Medicines in Development for Diabetes

Medicines in Development Diabetes 20122

*For more information about a specific medicine in this report, please call the telephone number listed.


Diabetes, type 1 anD type 2

product Name Sponsor Indication Development Status*

11ß-HSD inhibitor Bristol-Myers SquibbPrinceton, NJ

diabetes Phase II(800) 332-2056

AC 201(interleukin-1ß inhibitor)

Twi PharmaceuticalsTaipei, Taiwan

type 2 diabetes Phase IIwww.twipharma.com

AC 165198(fusion protein)

Amylin PharmaceuticalsSan Diego, CABioconBangalore, India

diabetes Phase I(858) 552-2200

Afrezza®

insulin inhalationMannKindValencia, CA

type 1 diabetes, type 2 diabetes application submitted(661) 775-5300

aleglitazar(PPAR a/g agonist)

RocheNutley, NJ

type 2 diabetes

--------------------------------------------------type 2 diabetes (combination therapy)

Phase III(973) 235-5000------------------------------------------- Phase I(973) 235-5000

alogliptin(DPP-IV inhibitor)

Takeda Pharmaceuticals U.S.A.Deerfield, IL

type 2 diabetes

--------------------------------------------------type 2 diabetes in adolescents and children

application submitted(877) 825-3327-------------------------------------------Phase I(877) 825-3327

alogliptin/metformin(fixed-dose combination)


type 2 diabetes application submitted(877) 825-3327

alogliptin/pioglitazone(fixed-dose combination)


type 2 diabetes application submitted(877) 825-3327

alogliptin/roflumilast Takeda Pharmaceuticals U.S.ADeerfield, IL

type 2 diabetes Phase I(877) 825-3327

alpha-1 antitrypsin Omni Bio PharmaceuticalGreenwood Village, CO

type 1 diabetes Phase I/IIwww.omnibiopharma.com

AMG 151(glucokinase stimulant)

AmgenThousand Oaks, CA

type 2 diabetes Phase II(800) 772-6436

AMG 876(fusion protein)

AmgenThousand Oaks, CA


Medicines in Development Diabetes 2012 3

Medicines in Development for Diabetes Medicines in Development for Diabetes


product Name Sponsor Indication Development Status

anagliptin(DPP-IV antagonist)

Kowa Research InstituteMorrisville, NC


analog insulin-PH20 Halozyme TherapeuticsSan Diego, CA

type 1 diabetes, type 2 diabetes Phase II(858) 794-8889

ARI-2243(DPP-IV antagonist)

Arisaph PharmaceuticalsBoston, MA


ASP-1941(SGLT2 inhibitor)

Astellas Pharma USDeerfield, IL


AV 133(imaging agent)

Avid RadiopharmaceuticalsPhiladelphia, PA

diabetes (diagnosis) Phase I(215) 298-0700

BGP-15(JNK inhibitor/insulin sensitiser)

N-Gene Research LaboratoriesNew York, NY


BI-135585(11ß-HSD1 inhibitor)

Boehringer Ingelheim PharmaceuticalsRidgefield, CT


BIOD-123(ultra-rapid-acting recombinant human insulin)

BiodelDanbury, CT


BIOD-125(ultra-rapid-acting recombinant human insulin)

BiodelDanbury, CT

type 1 diabetes Phase I completed(203) 796-5000

Byetta®

exenatideAmylin PharmaceuticalsSan Diego, CA

type 2 diabetes in adolescents Phase III(858) 552-2200

CA-18C3 XBiotechAustin, TX


canagliflozin(SGLT2 inhibitor)

Janssen Research & DevelopmentRaritan, NJ

type 2 diabetes application submittedwww.janssenrnd.com

canagliflozin/metforminextended-release(fixed-dose combination)

DepomedMenlo Park, CAJanssen Research & DevelopmentRaritan, NJ

type 2 diabetes Phase III(650) 462-5900www.janssenrnd.com

canagliflozin/metforminimmediate-release(fixed-dose combination)


type 2 diabetes Phase IIIwww.janssenrnd.com





CAT 1004 Catabasis PharmaceuticalsCambridge, MA


CCX140 ChemoCentryxMountain View, CA

type 2 diabetes(see also diabetes-related)

Phase II(650) 210-2900

cetilistat(lipase inhibitor)

NorgineAmsterdam, Netherlands

type 2 diabetes in clinically obese patients

Phase IIwww.norgine.com

CJC-1134-PC(GLP-1 stimulant)

ConjuChemLos Angeles, CA

type 2 diabetes Phase IIwww.conjuchem.com

CVX 096(PF-04856883)(GLP-1 receptor agonist)

PfizerNew York, NY


dapagliflozin(SGLT2 inhibitor)

AstraZenecaWilmington, DEBristol-Myers SquibbPrinceton, NJ

type 2 diabetes

-----------------------------------------------type 2 diabetes(combination therapy), type 2 diabetes(second-line therapy)

application submitted(800) 236-9933(800) 332-2056----------------------------------------Phase III(800) 236-9933(800) 332-2056

dapagliflozin/metformin(fixed-dose combination)


type 2 diabetes

------------------------------------------------type 2 diabetes (with extended-release metformin)

Phase III(800) 236-9933(800) 332-2056---------------------------------Phase I(800) 236-9933(800) 332-2056

DB 959(PPAR d/g agonist)

DARA BioSciencesRaleigh, NC


DC9703 Obio Pharmaceutical(Omega Bio-Pharma)Wilmington, DE

type 2 diabetes Phase Iwww.obiopharma.com

diabetes compound Eli LillyIndianapolis, IN













DSP-8658(PPAR a/g agonist)

Sunovion PharmaceuticalsMarlborough, MA


dulaglutide(GLP-1 analog)

Eli LillyIndianapolis, IN

type 2 diabetes Phase III(800) 545-5979

EGT-0001442(SGLT2 inhibitor)

TheracosMarlborough, MA


EGT-0001474(SGLT2 inhibitor)

TheracosMarlborough, MA


empagliflozin(SGLT2 inhibitor)

Boehringer Ingelheim PharmaceuticalsRidgefield, CTEli LillyIndianapolis, IN

type 2 diabetes Phase III(800) 243-0127(800) 545-5979

empagliflozin/linagliptin(fixed-dose combination)



empagliflozin/metformin(fixed-dose combination)



emricasan Conatus PharmaceuticalsSan Diego, CA

type 1 diabetes after islet cell transplantation

Phase I/IIwww.conatuspharma.com

encapsulated islet cell transplantation therapy

ViaCyteSan Diego, CA

type 1 diabetes Phase I/II(858) 455-3708

enclomifene Repros TherapeuticsThe Woodlands, TX

type 2 diabetes in men with second-ary hypogonadism or adult-onset idiopathic hypogonadotropichypogonadism

Phase II(281) 719-3400

ertugliflozin/PF-04971729(SGLT2 inhibitor)

PfizerNew York, NY


exenatide long-acting Hanmi PharmaceuticalSeoul, South Korea

type 2 diabetes Phase IIwww.hanmipharm.com

exenatide suspension Amylin PharmaceuticalsSan Diego, CA







gevokizumab(IL-1B inhibitor mAb)

XOMABerkeley, CA

type 1 diabetes, type 2 diabetes Phase II(510) 204-7200

GK1-399(TTP-399)(glucokinase activator)

Forest LaboratoriesNew York, NYTransTech PharmaHigh Point, NC

type 2 diabetes Phase I/II(800) 947-5227(336) 841-0300

GPR 119 agonist Bristol-Myers SquibbPrinceton, NJ


GSK256073(HM74A agonist)

GlaxoSmithKlineRsch. Triangle Park, NC


GSK1070806(IL-18 mAb)



GSK1614235(SGLT1 inhibitor)



GSK2330672(ileal bile acid transfer inhibitor)



HDV-insulin Diasome PharmaceuticalsConshohocken, PA


HE3286 Harbor BioSciencesSan Diego, CA


HIP-2B (human pro-islet peptide)

CureDMWilmington, DE

type 1 diabetes, type 2 diabetes Phase I(302) 288-0620

HPP-404(histamine H3 receptor antagonist)

High Point PharmaceuticalsHigh Point, NC

diabetes Phase Iwww.highpointpharma.com

HPP-593(PPAR d agonist)

High Point PharmaceuticalsHigh Point, NC

diabetes Phase Iwww.highpointpharma.com

Humalog® insulin lispro


type 1 diabetes, type 2 diabetes Phase III(800) 545-5979

IBC-VS01(insulin B-chain vaccine)

Orban BiotechBrookline, MA







Ilaris®

canakinumabNovartisEast Hanover, NJ

type 2 diabetes

------------------------------------------------type 1 diabetes

Phase II/III(888) 669-6682---------------------------------Phase II(888) 669-6682

indeglitazar(PLX-204)

PlexxikonBerkeley, CA


INGAP peptide ExsulinMinneapolis, MN

type 1 diabetes, type 2 diabetes Phase IIwww.exsulin.com

insulin adjustable basal BiodelDanbury, CT


insulin glargine (new formulation)

Sanofi USBridgewater, NJ

type 1 diabetes, type 2 diabetes Phase III(800) 981-2491

insulin oral sublingual BiodelDanbury, CT


insulin transdermal Transdermal GlobalBroomall, PA

type 1 diabetes, type 2 diabetes Phase Iwww.transdermalglobal.com

INT131(PPAR g modulator)

InteKrin TherapeuticsLos Altos, CA


ISIS-GCCRrx(glucocorticoid receptor antagonist)

Isis PharmaceuticalsCarlsbad, CA


ISIS-GCGRrx(glucagon receptor antagonist)



ISIS-PTP1Brx(PTP-1B gene inhibitor)



ISIS-SGLT2rx Isis PharmaceuticalsCarlsbad, CA


ITCA 650(exenatide subcutaneous implant)

Intarcia TherapeuticsHayward, CA


Janumet®sitagliptin/metformin

MerckWhitehouse Station, NJ

type 2 diabetes in adolescents and children

Phase III(800) 672-6372






Januvia®

sitagliptinMerckWhitehouse Station, NJ

type 2 diabetes in the elderly and adolescents

Phase III(800) 672-6372

JNJ-16269110(usistapide)


type 2 diabetes Phase II completedwww.janssenrnd.com

JNJ-41443532 Janssen Research & DevelopmentRaritan, NJ

type 2 diabetes Phase II completedwww.janssenrnd.com

KRP-104(CD26 antigen inhibitor)

ActivX BiosciencesLa Jolla, CA


LCQ908(DGAT1 inhibitor)

NovartisEast Hanover, NJ


LEZ763 NovartisEast Hanover, NJ


LIK066 NovartisEast Hanover, NJ


LIM-0705 Limerick BiopharmaSouth San Francisco, CA


linagliptin/pioglitazone(fixed-dose combination)



lisofylline(lysophosphatidic acid transferase inhibitor)

DiaKine TherapeuticsNorfolk, VA


lixisenatide(AVE0010)



lixisenatide/Lantus® insulin glargine(fixed-dose combination)



LX-4211(SLGT1/SLGT2 inhibitor)

Lexicon PharmaceuticalsThe Woodlands, TX


LY2409021(glucagon-R antagonist)








LY2523199(11ß-HSD1 inhibitor)



LY2605541novel basal insulin/insulin peglispro


type 1 diabetes, type 2 diabetes Phase III(800) 243-1027(800) 545-5979

LY2963016(new insulin glargine product)


type 1 diabetes, type 2 diabetes Phase III(800) 243-1027(800) 545-5979

MBX-2982(G-protein coupled receptor)

MetabolexHayward, CA


mesenchymal precursor cell (MPC) product(stem cell therapy)

MesoblastNew York, NY


metformin delayed-release formulation(gut sensory modulator)

Elcelyx TherapeuticsSan Diego, CA


metreleptin Amylin PharmaceuticalsSan Diego, CA

diabetes and/or hypertriglyceridemia in patients with inherited or acquired lipodystrophy--------------------------------------------------type 1 diabetes

application submitted(858) 552-2200

-------------------------------------------Phase I(858) 552-2200

mitiglinide Kissei AmericaParsippany, NJ

type 2 diabetes Phase III completed(973) 334-4400

Mitoglitazone™MSDC-0160(insulin sensitizer)

Metabolic Solutions DevelopmentKalamazoo, MI


MK-3102(DPP-IV inhibitor)



MK-5823 MerckWhitehouse Station, NJ


MSDC-0602(insulin sensitizer)

Metabolic Solutions DevelopmentKalamazoo, MI






NN1218(insulin aspart fast-acting)

Novo NordiskPrinceton, NJ


NN1953(insulin oral)



NN1954(insulin oral)



NN9068(insulin degludec/liraglutide)



NN9924(GLP-1 receptor agonist)



NN9926(GLP-1 stimulant)



NP-500 Napo PharmaceuticalsSan Francisco, CA

type 2 diabetes(see also diabetes-related)

Phase I(415) 371-8300

OAP-189(PF-05212389)

PfizerNew York, NY


onglyza™saxagliptin


type 2 diabetes in adolescents and children

Phase III(800) 236-9933(800) 332-2056

oral-lyn™ insulin oral

Generex BiotechnologyToronto, Canada


oxyntomodulin MerckWhitehouse Station, NJ


PAZ-320 Boston TherapeuticsManchester, NH


PB-1023(GLP-1 receptor agonist)

PhaseBio PharmaceuticalsMalvern, PA


PEG-FGF-21 Bristol-Myers SquibbPrinceton, NJ

diabetes in clinical trials(800) 332-2056





peptide p277(orphan Drug)

Andromeda BiotechNess Ziona, Israel

type 1 diabetes (newly diagnosed) Phase IIIwww.andromedabio.com

PF-04937319 PfizerNew York, NY






prochymal®remestemcel-L

Osiris TherapeuticsColumbia, MD


Qnexa®

phentermine/topiramate VIVUSMountain View, CA

type 2 diabetes in obese patients Phase II(650) 934-5200

Ranexa®

ranolazine extended-releaseGilead SciencesFoster City, CA


RG4929(11ß-HSD inhibitor)

RocheNutley, NJ


RG7201(SGLT2 inhibitor)

RocheNutley, NJ


RG7426(BHT-3021)

Bayhill TherapeuticsPalo Alto, CAGenentechSouth San Francisco, CA

type 1 diabetes Phase I completed(650) 320-2800 (800) 626-3553

RG7685(GLP-1/GIP dual agonist)

RocheNutley, NJ


RM-493(MC4R peptide)

Rhythm PharmaceuticalsBoston, MA


Ryzodeg®

insulin degludec plusinsulin aspart


type 1 diabetes, type 2 diabetes application submitted(800) 727-6500

S-707106 ShionogiFlorham Park, NJ






semaglutide(NN9535)



sitagliptin/atovastatin(fixed-dose combination)



SLX-4090(MTP inhibitor)

Kadmon PharmaceuticalsWarrendale, PA

diabetes Phase II(724) 778-6100

SRT2104(SIRT1 protein stimulant)

Sirtris (GlaxoSmithKline)Cambridge, MA








Syncria®

albiglutide(GLP-1 agonist)



T2 18C3(mAb)

XBiotechAustin, TX


TAK-329(glucokinase stimulant)



TAK-472(DPP-IV antagonist)



TAK-875(GPR40 agonist)



taurocholic acid Satiogen PharmaceuticalsSan Diego, CA

type 2 diabetes Phase I/IIwww.satiogen.com

teneligliptin(DPP-IV antagonist)

Mitsubishi Pharma AmericaWarren, NJ

type 2 diabetes Phase Iwww.mt-pharma-america.com

teplizumab(orphan Drug)

MacroGenicsRockville, MD






tresiba®

insulin degludecNovo NordiskPrinceton, NJ

type 1 diabetes, type 2 diabetes

------------------------------------------------type 1 diabetes in adolescents and children

application submitted(800) 727-6500---------------------------------Phase III(800) 727-6500

TT-401(GLP-1 receptor agonist)

Transition TherapeuticsToronto, Canada


TTP054(GLP-1 receptor agonist)

TransTech PharmaHigh Point, NC


TTP355(glucokinase stimulant)

Forest LaboratoriesNew York, NYTransTech PharmaHigh Point, NC

type 2 diabetes Phase I(800) 947-5227(336) 841-0300

TTP814(PTP-1ß inhibitor)

TransTech PharmaHigh Point, NC


Victoza®

liraglutideNovo NordiskPrinceton, NJ

type 2 diabetes in adolescents and children------------------------------------------------type 1 diabetes

Phase III(800) 727-6500---------------------------------Phase II(800) 727-6500

vildagliptin NovartisEast Hanover, NJ

type 2 diabetes

------------------------------------------------type 2 diabetes in treatment-naïve patients

Phase III(888) 669-6682---------------------------------Phase II/III(888) 669-6682

vildagliptin/metformin(fixed-dose combination)

NovartisEast Hanover, NJ

type 2 diabetes Phase III completed(888) 669-6682

VRS-859(GLP-1 agonist)

Diartis PharmaceuticalsRedwood City, CA


VVP808(insulin sensitizer)

Verva PharmaceuticalsCarlsbad, CA


ZP2929 (GLP-1 receptor agonist)

Boehringer Ingelheim PharmaceuticalsRidgefield, CTZealand PharmaCopenhagen, Denmark

type 2 diabetes Phase I(800) 243-0127www.zealandpharma.com



Diabetes-RelateD ConDitions


ABT-335(choline fenofibrate)

Abbott LaboratoriesAbbott Park, IL

diabetic macular edema Phase II completed(847) 937-6100

ABT-639(T-type calcium channel antagonist)


diabetic neuropathy Phase II(847) 937-6100

ABT-652(histamine H3 receptor modulator)



ACT-1 topical gel FirstString ResearchMount Pleasant, SC

diabetic foot ulcers Phase II(843) 860-8372

AKB-9778(HPTPß inhibitor/Tie-2 receptor activator)

Aerpio TherapeuticsCincinnati, OH

diabetic macular edema Phase I(513) 985-1920

AL-39,324(tyrosine kinase inhibitor)

AlconFort Worth, TX

diabetic retinopathy Phase I/II(800) 862-5266

ALG-1001(small peptide therapy)

Allegro OphthalmicsSan Juan Capistrano, CA

diabetic macular edema Phase I/II(949) 940-8130

AmiKet™amitriptyline/ketamine

EpiCeptTarrytown, NY


ARA 290(erythropoietin receptor agonist)

Araim PharmaceuticalsOssining, NY


ARC-4558(clonidine topical gel)

Aricon TherapeuticsBaltimore, MD

diabetic neuropathy(Fast Track)

Phase II completed(410) 522-8701

atrasentan(selective endothelin A receptor antagonist)


diabetic nephropathy Phase II(847) 937-6100

baricitinib(JAK1/JAK2 inhibitor)

Eli LillyIndianapolis, INIncyteWilmington, DE


BVS857 Novartis PharmaceuticalsEast Hanover, NJ

insulin resistance Phase I(888) 669-6682

C-peptide long-acting CebixLa Jolla, CA

diabetic neuropathy(Fast Track)

Phase I/II(858) 729-6500





carisbamate Janssen Research & DevelopmentRaritan, NJ

diabetic neuropathy Phase II completedwww.janssenrnd.com

CCX140 ChemoCentryxMountain View, CA

diabetic nephropathy(see also diabetes)

Phase II(650) 210-2900

Cogenzia™gentamicin-collagen sponge

InnocollAshburn, VA

diabetic foot ulcers Phase IIIwww.innocollinc.com

CORT001 CortendoHalmstad, Sweden

metabolic syndrome Phase IIwww.cortendo.com

CTP-499 Concert PharmaceuticalsLexington, MA


darapladib GlaxoSmithKlineRsch. Triangle Park, NC

diabetic macular edema Phase II(888) 825-5249

dextromethorphan/quinidine(fixed-dose combination)

Avanir PharmaceuticalsAliso Viejo, CA

diabetic neuropathy Phase IIIwww.avanir.com

DSC-127 Derma SciencesPrinceton, NJ


EVK-001(intranasal dopamine-receptor antagonist)

Evoke PharmaSan Diego, CA

diabetic gastroparesis Phase II(858) 967-5454

eylea®

afiliberceptBayer HealthCare PharmaceuticalsWayne, NJRegeneron PharmaceuticalsTarrytown, NY

diabetic macular edema Phase III(888) 842-2937(914) 847-7000

GRT 6005/06 Forest LaboratoriesNew York, NY


GSK962040(motilin receptor agonist)



HO-0303(protein kinase C inhibitor/stimulant)

HealOrNess Ziona, Israel

diabetic foot ulcers Phase II/IIIwww.healor.com

ICO-007(antisense oligonucleotide)

iCo TherapeuticsVancouver, Canada






Iluvien®

fluocinolone acetonideAlimera SciencesAlpharetta, GApSividaWatertown, MA

diabetic macular edema(Fast Track)

application submitted(678) 990-5740(617) 926-5000

iroxanadine OrphazymeCopenhagen, Denmark

diabetic foot ulcers, diabetic neuropathy

Phase Iwww.orphazyme.com

losartan/thioctic acid(INV-144)

InVasc TherapeuticsTucker, GA


Lucentis®

ranibizumab implant(sustained delivery)

GenentechSouth San Francisco, CAForSight Vision4Menlo Park, CA

diabetic macular edema Phase I(800) 626-3553

LY2382770(TGF-b mAb)



LY2623091(MR antagonist)


renal disease associated with diabetes

Phase II(800) 545-5979

Macugen®

pegaptanibEyetechPalm Beach Gardens, FL

diabetic macular edema (Fast Track),diabetic retinopathy

Phase IIIwww.eyetech.com

MK-6096(dual orexin receptor antagonist)



modified hepatocyte growth factor gene therapy

ViroMedSeoul, South Korea

diabetic nephropathy Phase I/IIwww.viromed.com

NanoDoX®

doxycycline topical gelNanotherapeuticsAlachua, FL


nemonoxacin TaiGen BiotechnologyTaipei, Taiwan

infections associated with diabetic foot ulcers

Phase II completedwww.taigenbiotech.com

Nexagon®

antisense oligonucleotideCoDa TherapeuticsSan Diego, CA


Nova63035(dexamethasone prodrug emulsion)

Novagali PharmaEvry, France

diabetic macular edema Phase I/IIwww.novagali.com

NP-500 Napo PharmaceuticalsSan Francisco, CA

metabolic syndrome (see also diabetes)

Phase I(415) 371-8300





ocriplasmin ThromboGenicsIselin, NJ

diabetic retinopathy Phase II(732) 590-2900

optina™danazol low-dose

Ampio PharmaceuticalsGreenwood Village, CO


ozurdex®

dexamethasone intravitreal implant

AllerganIrvine, CA

diabetic macular edema Phase III(714) 246-4500

pexiganan Dipexium PharmaceuticalsNew York, NY

diabetic foot ulcers application submitted(212) 618-1415

PF-655 (RTP801i14)

Quark PharmaceuticalsFremont, CA


PF-00489791(phosphodiesterase 5 inhibitor)

PfizerNew York, NY



diabetic nephropathy Phase I(800) 879-3477

pyridorin™pyridoxamine

NephrogenexRsch. Triangle Park, NC

diabetic nephropathy(Fast Track)

Phase II(609) 986-1780

Qutenza®

capsaicin dermal patchAstellas Pharma USDeerfield, ILNeurogesXSan Mateo, CA

diabetic neuropathy Phase III(800) 695-4321(650) 358-3300

ranirestat(AS-3201)

EisaiWoodcliff Lake, NJ

diabetic neuropathy Phase III(888) 274-2378

RM-131(ghrelin peptide agonist)

Rhythm PharmaceuticalsBoston, MA


safotibant (FOV2304)(bradykinin ß1 antagonist)



SAR164653(cathepsin A inhibitor)


cardiovascular-related complications and death in diabetic patients

Phase I(800) 981-2491

SAR407899(Rho kinase inhibitor)







sirolimus ophthalmic MacuSightUnion City, CA

diabetic macular edema (subconjunctival) (Fast Track)------------------------------------------------diabetic macular edema (intravitreous)

Phase II (510) 400-1440---------------------------------Phase I(510) 400-1440

SKL-NP SK Life ScienceFair Lawn, NJ

diabetic neuropathic pain Phase II(201) 421-3864

TAK-428(nerve growth factor agonist)



TTPABC TransTech PharmaHigh Point, NC


TV1001(low-dose sodium nitrate)

TheraVascCleveland, OH

diabetic angiopathy Phase II(318) 349-3851

TZP-102(ghrelin agonist)

Tranzyme PharmaDurham, NC

diabetic gastroparesis(Fast Track)

Phase II/III(919) 474-0020

Vasaloc™danazol low-dose

Ampio PharmaceuticalsGreenwood Village, CO


white blood cell therapy(intralesional)

MacrocureTikva, Israel

diabetic foot ulcers Phase IIIwww.macrocure.com

Application Submitted

Phase III

Phase II

Phase I 85

94

42

11

* Some medicines are listed in more than one phase of development.

Medicines in developMent for diabetes and diabetes-related conditions by phase of developMent*


application submitted—An application for marketing has been submitted by the company to the Food and Drug Administration (FDA).

diabetes—A chronic disease in which the body does not produce or properly use insulin, a hormone that is needed to convert sugar, starches and other food into energy needed for daily life. Symptoms may include excessive thirst, hunger, urination and weight loss. The cause of diabetes continues to be a mystery, although both genetics and environmental fac-tors such as obesity and lack of exercise ap-pear to play roles. type 1 diabetes, the more severe form, results from the body’s failure to produce insulin, which “unlocks” the cells of the body, allowing glucose to enter and fuel them. It is estimated that 5 percent to 10 percent of Americans who are diagnosed with diabetes have type 1, which requires insulin treatment. type 2 diabetes results from insulin resistance (a condition in which the body fails to properly use insulin), combined with relative insulin deficiency. Most Americans who are diagnosed with diabetes have type 2, which in most cases can be controlled if treated properly by a com-bination of dietary measures, weight loss, and oral medication.

diabetic angiopathy—Similar to most com-plications brought about by diabetes, diabetic angiopathy is primarily due to hyperglycemia or the high levels of blood sugar known as glucose. Angiopathy can occur in any part of the body where the effect of high glucose levels result in the build up of plaque in the inner walls of the vessels. There are two types of the disease—macroangiopathy or microan-giopathy. In macroangiopathy, atherosclerosis and a resultant blood clot forms on the large blood vessels, sticks to the vessel walls, and blocks the flow of blood. Macroangiopathy may cause other complications, such as ischemic heart disease, stroke, and peripheral vascular disease, which contributes to the diabetic foot ulcers and the risk of amputation. In microan-giopathy, the walls of the smaller blood vessels become so thick and weak that they bleed, leak protein, and slow the flow of blood through the body. The decrease of blood flow through clot formation impairs the flow of oxygen to cells

and biological tissues (called ischemia) and leads to cellular death (necrosis and gangrene, which in turn may require amputation). Thus, tissues which are very sensitive to oxygen levels, such as the retina, develop microan-giopathy and may cause blindness (so-called proliferative diabetic retinopathy). Damage to nerve cells may cause peripheral neuropathy, and to kidney cells, diabetic nephropathy.

diabetic gastroparesis—A disorder affecting people with both type 1 and type 2 diabetes in which the stomach takes too long to empty its contents (delayed gastric emptying). The vagus nerve controls the movement of food through the digestive tract. If the vagus nerve is damaged or stops working, the muscles of the stomach and intestines do not work nor-mally, and the movement of food is slowed or stopped. Just as with other types of neuropathy (nerve damage), diabetes can damage the vagus nerve if blood glucose levels remain high over a long period of time. High blood glu-cose causes chemical changes in nerves and damages the blood vessels that carry oxygen and nutrients to the nerves. Gastroparesis can make diabetes worse by making it more dif-ficult to manage blood glucose. When food that has been delayed in the stomach finally enters the small intestine and is absorbed, blood glucose levels rise. If food stays too long in the stomach, it can cause problems like bacterial overgrowth because the food has fermented. Also, the food can harden into solid masses, called bezoars, that may cause nausea, vomit-ing, and obstruction in the stomach. Bezoars can be dangerous if they block the passage of food into the small intestine.

diabetic nephropathy—Kidney disease or damage that can occur in people with diabetes. The kidneys have many tiny blood vessels that filter waste from the blood. High blood sugar from diabetes can destroy those blood vessels. Over time, the kidney isn’t able to do its job as well and may stop working completely, which is called kidney failure. Out of 100 people with diabetes, as many as 40 will develop kidney damage. Currently, diabetic nephropathy is the leading cause of chronic kidney disease in the United States and other Western societies.

It is also one of the most significant long-term complications in terms of morbidity and mortality for individual patients with diabetes, which is responsible for up to 40 percent of all end-stage renal disease (ESRD) cases in the United States.

diabetic neuropathy—Nerve damage in the arms, hands, legs, and feet caused by diabetes. The condition develops slowly and worsens over time. Depending on the types of nerves involved, one or more signs and symptoms may be present in diabetic periph-eral neuropathy. Sensory neuropathy results in numbness or tingling in the feet or pain or discomfort in the feet or legs, including prickly, sharp pain or burning feet. Motor neuropathy involves muscle weakness and loss of muscle tone in the feet and lower legs, loss of balance, or changes in foot shape that can lead to areas of increased pressure. Autonomic neuropathy results in dry feet and cracked skin. The loss of sensation and other problems associated with nerve damage make a patient prone to developing skin ulcers (open sores) that can become infected and may not heal. This seri-ous complication of diabetes can lead to the loss of a foot, a leg, or even a life.

diabetic retinopathy—The most common diabetic eye disease and a leading cause of blindness in American adults. It is caused by changes in the blood vessels of the retina, the light sensitive tissue at the back of the eye that is necessary for good vision. In some people with diabetic retinopathy, blood vessels may swell and leak fluid. In others, abnormal new blood vessels grow on the surface of the retina. Over time, diabetic retinopathy, which usually affects both eyes, can worsen and cause vision loss. The condition has four stages: 1) mild nonproliferative retinopathy, the earliest stage during which microaneurysms occur in the retina’s tiny blood vessels; 2) moder-ate nonproliferative retinopathy, during which some blood vessels that nourish the retina are blocked; 3) severe nonproliferative retinopathy, when many more blood vessels are blocked and deprive several areas of the retina with their blood supply; and 4) proliferative retinopa-thy, the advanced stage when signals sent by

Glossary


Glossary

The content of this report has been obtained through industry sources and the Adis “R&D Insight” database based on the latest information. Report current as of October 9, 2012. The information 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 web site.

A publication of phRMA’s Communications & public Affairs Department. (202) 835-3460

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the retina for nourishment trigger the growth of new blood vessels, which grow along the retina and the surface of the clear, vitreous gel that fills the inside of the eye. If those thin, fragile blood vessels leak blood, severe vision loss and even blindness can result. Up to 45 percent of Americans diagnosed with diabetes have some stage of diabetic retinopathy.

diabetic ulcers—The most common foot injuries leading to lower extremity amputation. The vast majority of diabetic foot complications resulting in amputation begin with the forma-tion of skin ulcers. The three main causes of diabetic foot ulcers are: neuropathy, poor blood supply, and infection. Up to 15 percent of diabetics are likely to develop a foot ulcer at some stage in their lives. Early detection and appropriate treatment of those ulcers may prevent up to 85 percent of amputations. The risk of lower extremity amputation is 15 to 46 times higher in diabetics than in people who do not have the disease.

insulin resistance—A generalized metabolic disorder caused by the body’s inability to use insulin efficiently. Some people are genetically

predisposed to insulin resistance. Acquired factors, such as excess body fat and physical inactivity, also can elicit insulin resistance. Most people with insulin resistance have abdomi-nal obesity. The biologic mechanisms at the molecular level between insulin resistance and metabolic risk factors aren’t fully understood and appear to be complex.

macular edema—A condition in which fluid can leak into the center of the macula, the part of the eye where sharp, straight-ahead vision occurs. The fluid makes the macula swell, thus blurring vision. It can occur at any stage of diabetic retinopathy, although it is more likely to occur as the disease progresses. About half of the people with proliferative retinopathy also have macular edema.

metabolic syndrome—A group of meta-bolic risk factors that raise the risk of type 2 diabetes in one person, including: abdominal obesity (excessive fat tissue in and around the abdomen); atherogenic dyslipidemia (blood fat disorders—high triglycerides, low HDL choles-terol, and high

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, determine a safe dosage range, and identify potential side effects.

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.

phase III—The drug is given to a larger, more diverse patient population, often involving be-tween 1,000 and 3,000 patients (but sometime many more thousands), to generate statistically significant evidence to confirm its safety and effectiveness. They are the longest studies, and usually take place in multiple sites around the world.


Selected Facts About Diabetes in the United States*

• In the United States, 25.8 million people, or nearly 8.3 percent of the population, have diabetes. An estimated 18.8 million have been diagnosed, but 7 million people are not aware that they have the disease. Another 79 million have pre-diabetes.

• In 2010, 1.9 million new cases of diabetes were diagnosed in people ages 20 and older. In that age group, 11.3 percent, or 25.6 million people, have diabetes—13 million men and 12.6 million women.

• In young people under the age of 20, 215,000, or 0.26 percent, have diabetes. About 1 in every 400 children and adolescents has diabetes. Non-Hispanic white youth have the highest rate of new cases of type 1 diabetes (24.8 per 100,000 per year among those younger than age 10 and 22.6 per 100,000 per year among those ages 10–19).

• Among those people age 65 years and older, 10.9 million, or 26.9 percent, have diabetes. In 2004, heart disease was noted on 68 percent and stroke on 16 percent of diabetes-related death certificates among that age group.

• The 2007-2009 national survey data for people diagnosed with diabetes ages 20 and older found the following prevalence of diabetes by race and ethnicity: 7.1 percent of non-Hispanic whites, 8.4 percent of Asian Americans, 12.6 percent of non-Hispanic blacks, and 11.8 percent of Hispanics. Among Hispanics, the prevalence rates were 7.6 percent for Cubans, 13.3 percent for Mexican Americans, and 13.8 percent for Puerto Ricans.

• Diabetes is the seventh leading cause of death in the United States. In 2007, diabetes was listed as the underlying cause on 71,382 death certifi-cates and as a contributing factor on an additional 160,022 death certificates, which means that diabetes contributed to a total of 231,404 deaths.

Diabetes1

Sources:

Costs1

Diabetes-Related Conditions

1. American Diabetes Association, www.diabetes.org 2. Agency for Healthcare Research and Quality, www.ahrq.gov

• The total annual economic cost of diabetes in 2007 was $174 billion. Direct medical costs totaled $116 billion, while indirect costs (including disability, work loss, and premature mortality) came to $58 billion. If the additional costs of undiagnosed diabetes ($18 billion), prediabetes ($25 billion), and gestational diabetes ($623 million) were factored in, the total cost of diabetes in the United States adds up to $218 billion.

• Average medical expenditures among people with diagnosed diabetes are 2.3 times higher than expenditures for people who don’t have diabetes.

• Each year, about 1 percent to 4 percent of people with diabetes develop a foot ulcer, and 10 percent to 15 percent of those with diabetes will have at least one foot ulcer during their lifetimes. Lower extremity amputations (LEAs) are an extreme complication associated with diabetes and foot ulcers. In the United States, nearly 80,000 LEAs are performed on diabetics each year. In 2005, the overall rate of hospital discharges for new LEAs was about 4.3 per 1,000 people with diabetes compared with a rate of about 0.3 per 1,000 in the general population.2

• Adults with diabetes have heart disease death rates and stroke risk at about 2 to 4 times higher than adults without diabetes. In 2004, heart disease was noted on 68 percent of diabetes-related death certificates among people ages 65 years and older, while stroke was noted on 16 percent of diabetes-related death certificates among that age group.1

• Diabetes is the leading cause of kidney failure, accounting for 44 percent of new cases in 2008. That year, 48,374 people with diabetes began treatment for end-stage kidney disease, and another 202,290 people with end-stage kidney disease due to diabetes were living on chronic dialysis or with a kidney transplant in the United States.1

• About 60 percent to 70 percent of people with diabetes have mild to severe forms of nervous system damage (diabetic neuropathy).1

• Diabetes is the leading cause of new cases of blindness among adults ages 20–74. From 2005-2008, 4.2 million people with diabetes (28.5 percent) age 40 and older had diabetic retinopathy, and of those, almost 0.7 million (4.4 percent) had advanced diabetic retinopathy that could lead to severe vision loss.1

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 experimental 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 compounds 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 2007 study by the Tufts Center for the Study of Drug Development.Once a new compound has been identified in the laboratory, medicines are usually devel-oped as follows:preclinical testing. A pharmaceutical com-pany conducts laboratory and animal studies to show biological activity of the compound against the targeted disease, and the com-pound is evaluated for safety.Investigational New Drug Application (IND). After completing preclinical testing, a company 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 manufactured. All clinical trials must be reviewed and approved 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, determine 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 iseffective, 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 generate

statistically significant evidence to confirm its safety and effectiveness. They are the longest 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 physicians 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 $49.5 billion in research and development in 2011.

The Drug Discovery, Development and Approval Process

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

Health & Medicine

PhRMA Report 2012: Medicines in Development for Diabetes