LZHEIMER ÕS D ISE A SE … · 4 Medicines in Development Alzheimer’s Disease 2012...

Today, more than 5 million Americans are suf-fering from Alzheimer’s disease. The disease ravages the minds of patients, crushes entire families and currently costs the health care system $200 billion a year. These sobering statistics are projected to get much worse as the 76 million American baby boomers age.If no new medicines are found to prevent, delay or stop the progression of Alzheimer’s disease, the number of people affected in America will jump to 13.5 million by 2050, according to the Alzheimer’s Association. Costs for care for Alzheimer’s patients will

Even modest progress can drastically change this trajectory. A breakthrough medicine that delays the onset of Alzheimer’s disease by

Americans suffering from the disease in 2050 by 43 percent and the related costs of care by $447 billion. Hope for the future lies in medical innovation.America’s biopharmaceutical companies cur-rently have 93 medicines in development for Alzheimer’s disease and dementias—either in

human clinical trials or awaiting U.S. Food and Drug Administration (FDA) review. They are exploring various new approaches to treating Alzheimer’s disease, including:

accumulation of amyloid-beta and tau protein deposits.

penetrate the blood-brain barrier for mild cognitive impairment, a precursor to Alzheimer’s.

Alzheimer’s disease.

takes, on average, more than $1 billion and 10 to 15 years to develop a new medicine. But

knowledge, and researchers are using every cutting-edge tool at their disposal. With contin-ued dedication, we hope to make a difference for every person at risk of suffering from this terrible, debilitating disease.

Biopharmaceutical Research Companies are

Developing Nearly 100 Medicines for Alzheimer’s

Disease and Other Dementias

Medicines in Development

ALZHEIMER’S DISEASEPRESENTED BY AMERICA’S BIOPHARMACEUTICAL RESEARCH COMPANIES

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Medicines in Development

For Alzheimer’s Disease*

* Some medicines are in development for more than one disorder.

Medicines in Development Alzheimer’s Disease 20122

Medicines in Development for Alzheimer’s Disease

ALZHEIMER’S DISEASE AND DEMENTIAS

Product Name Sponsor Indication Development Status*

AAB-002(amyloid beta-protein inhibitor mAb)

Janssen Alzheimer ImmunotherapySouth San Francisco, CA

New York, NY

Alzheimer’s disease Phase 0

(amyloid beta-protein inhibitor mAb)


New York, NY

Alzheimer’s disease Phase I

ABT-126(alpha-7 neuronal nicotinicreceptor antagonist)

Abbott LaboratoriesAbbott Park, IL

mild to moderate Alzheimer’s disease

--------------------------------------------------Alzheimer’s disease (combination therapy), Alzheimer’s disease (elderly)

Phase II

-------------------------------------------Phase I

(neurotransmitter receptor modulator)


Alzheimer’s disease Phase II


mild to moderate Alzheimer’s disease Phase II

ABT-560(alpha-4 beta-2 nicotinic receptor modulators)


cognitive disorders Phase I

ABT-957(calpain inhibitor)



ACC-002(amyloid-beta peptide conjugate)


New York, NY

Alzheimer’s disease Phase 0

AD02 vaccineVienna, AustriaGlaxoSmithKlineRsch. Triangle Park, NC


AD03 vaccineVienna, AustriaGlaxoSmithKlineRsch. Triangle Park, NC


Medicines in Development Alzheimer’s Disease 2012 3



Product Name Sponsor Indication Development Status

(donepezil/memantine)Adamas PharmaceuticalsEmeryville, CA

moderate to severe Alzheimer’s disease

Phase II(510) 450-3500

APH-0703 AphiosWoburn, MA

Alzheimer’s disease, cognitive disorders

Phase I/II

ARC029(soluble amyloid reducing/clearing agent)(Orphan Drug)

Archer PharmaceuticalsSarasota, FL

mild to moderate Alzheimer’s disease Phase I(941) 755-6644

ARC031(soluble amyloid reducing/clearing agent)

Archer PharmaceuticalsSarasota, FL

Alzheimer’s disease Phase I(941) 755-6644

ASP0777 Astellas Pharma US dementia associated with Alzheimer’s disease

Phase I

AVN 101(serotonin 6 receptor antagonist)

Avineuro PharmaceuticalsSan Diego, CA

cognitive enhancer in Alzheimer’s disease

Phase II

AVN 322(serotonin 6 receptor antagonist)

Avineuro PharmaceuticalsSan Diego, CA


AVN 397 Avineuro PharmaceuticalsSan Diego, CA


AZD1446(alpha4/beta2 neuronal nicotinic receptor agonist)

AstraZenecaWilmington, DETargaceptWinston-Salem, NC


(ispronicline)AstraZenecaWilmington, DETargaceptWinston-Salem, NC


AZD4694

radiopharmaceutical)

Navidea BiopharmaceuticalsDublin, OH

Alzheimer’s disease (diagnosis) Phase II(614) 793-7500

AZD5213(histamine-3 receptor antagonist)

AstraZenecaWilmington, DE






ß secretase inhibitor Eli LillyIndianapolis, IN

Alzheimer’s disease Phase II(800) 545-5979

BAN2401(amyloid beta-protein inhibitor)

BioArtic NeuroscienceStockholm, SwedenEisaiWoodcliff Lake, NJ

mild to moderate Alzheimer’s disease Phase Iwww.bioarti.se(888) 274-2378

bapineuzumab subcutaneous (AAB-001)


New York, NY

Alzheimer’s disease(subcutaneous)

Phase II(888) 381-4595(800) 879-3477

BCI-632 BrainCellsSan Diego, CA


BCI-838 BrainCellsSan Diego, CA


BIIB037(amyloid beta-protein inhibitor)

Biogen IdecCambridge, MA


bisnorcymserine(BNC)

QR PharmaBerwyn, PA


BMS-241027(microtubule stabilizer)

Bristol-Myers SquibbPrinceton, NJ

Alzheimer’s disease, tauopathies Phase I(800) 332-2056

BMS-708163(avagacestat)



BMS-932481(gamma secretase modulator)



BMS-933043(a-7 nicotinic agonist)


cognitive impairment Phase I(800) 332-2056

CAD106(amyloid beta-protein inhibitor)

Novartis PharmaceuticalsEast Hanover, NJ


CERE-110(AAV-NGF gene therapy)

CeregeneSan Diego, CA


CHF-5074(amyloid precursor protein secretase modulator)

Chiesi PharmaceuticalsRockville, MD

mild cognitive impairment Phase II(301) 424-2661





crenezumab(anti-Abeta)

GenentechSouth San Francisco, CA


CTS-21166(ß-secretase inhibitor)

Astellas Pharma US

CoMentisSouth San Francisco, CA


(650) 359-2600

CX717 Cortex PharmaceuticalsIrvine, CA

Alzheimer’s disease Phase II completed(949) 727-3157

davunetide intranasal Allon TherapeuticsVancouver, Canada

Alzheimer’s disease, mild cognitiveimpairment

Phase II(604) 736-0634

docosahexaenoic acid(DHA)

Martek BiosciencesParsippany, NJ

Alzheimer’s disease Phase III

(PPAR / agonist)Sunovion PharmaceuticalsMarlborough, MA


E2212(amyloid precursor protein secretase modulator)

EisaiWoodcliff Lake, NJ


E2609(BACE1 protein inhibitor)

EisaiWoodcliff Lake, NJ


ELND005(amyloid beta-protein inhibitor)

Elan South San Francisco, CATransition TherapeuticsToronto, Canada

mild to moderate Alzheimer’s disease(Fast Track)

Phase II

(416) 260-7770

EVP-0962(amyloid precursor proteinsecretase modulator)

EnVivo PharmaceuticalsWatertown, MA


EVP-6124 EnVivo PharmaceuticalsWatertown, MA

mild to moderate Alzheimer’s disease Phase II(617) 225-4250

Exebryl-1® ProteoTechKirkland, WA


(molecular imaging agent)Piramal HealthcareMumbai, India

Alzheimer’s disease (diagnosis) Phase IIIwww.piramalhealthcare.com

(PET imaging agent)GE HealthcareWaukesha, WI

Alzheimer’s disease (diagnosis) Phase IIIwww.gehealthcare.com





Gammagard®

immune globulin intravenous (human), 10% solution

Baxter Healthcare early-stage Alzheimer’s disease, mid-stage Alzheimer’s disease

Phase III

gantenerumab(RG1450)

RocheNutley, NJ

prodromal Alzheimer’s disease Phase II/III(973) 235-5000

GSK239512 GlaxoSmithKlineRsch. Triangle Park, NC

Alzheimer’s disease Phase II completed

GSK742457(5HT6 antagonist)

GlaxoSmithKlineRsch. Triangle Park, NC

Alzheimer’s disease Phase II completed

GSK933776A(anti-B amyloid mAb)

GlaxoSmithKlineRsch. Triangle Park, NC

Alzheimer’s disease Phase I completed

(BACE1 inhibitor)High Point PharmaceuticalsHigh Point, NC


human immunoglobulin(intravenous)

Grifols USALos Angeles, CA


immune globulin high dose Octapharma USAHoboken, NJ

Alzheimer’s disease (elderly) Phase II completed(201) 604-1130

irdabisant(CEP-26401)

CephalonFrazer, PA

cognitive dysfunction associated with Alzheimer’s disease

Phase I(610) 344-0200

LMTX(TRx-0237)

TauRx PharmaceuticalsSingapore

mild to moderate Alzheimer’s disease Phase Iwww.taurx.com

LNK-754 Link MedicineWaltham, MA

mild Alzheimer’s disease Phase I completed

Lundbeck Alzheimer’s disease Phase II

MithridionMadison, WI

autosomal dominant Alzheimer’s disease

Phase Iwww.mithridion.com

MK-3134 MerckWhitehouse Station, NJ

dementia Phase I completed

(PET tracer)MerckWhitehouse Station, NJ

Alzheimer’s disease (diagnosis) Phase I completed

(BACE1 inhibitor)MerckWhitehouse Station, NJ






MSDC-0160 Metabolic Solutions DevelopmentCompanyKalamazoo, MI


NIC5-15 HumaneticsMinneapolis, MN


PF-05212377(SAM-760) New York, NY


pioglitazonecompanion diagnostic

Takeda Pharmaceuticals U.S.A.

Zinfadel PharmaceuticalsChapel Hill, NC

Alzheimer’s disease (diagnosis) Phase I

Posiphen™R-phenserine

QR PharmaBerwyn, PA

Alzheimer’s disease,mild cognitive impairment

Phase II(610) 727-3913

PRX-3140(5-HT4 partial agonist)

NanotherapeuticsAlachua, FL


RG1577(MAO-B inhibitor)

RocheNutley, NJ


RG1662 (GABAA a5 receptor modulator)

RocheNutley, NJ

cognitive disorders Phase I(973) 235-5000

RG7129(BACE1 protein inhibitor)

RocheNutley, NJ


rilapladib GlaxoSmithKlineRsch. Triangle Park, NCHuman Genome SciencesRockville, MD


(BET protein inhibitor)ResverlogixCalgary, Canada


(H3 antagonist) Bridgewater, NJAlzheimer’s disease Phase II

Bridgewater, NJAlzheimer’s disease Phase I

sGC-1061 sGC PharmaWellesley, MA

Alzheimer’s disease Phase I (613) 791-4464





solanezumab Eli LillyIndianapolis, IN


ST-101 Sonexa TherapeuticsSan Diego, CA


SYN-120 Biotie TherapiesSouth San Francisco, CA

cognitive disorders associated with Alzheimer’s disease

Phase I completed

Toyama ChemicalTokyo, Japan

mild to moderate Alzheimer’s disease Phase II completedwww.toyama-chemical.co.jp

TC-5619 TargaceptWinston-Salem, NC


(5-HT4 agonist)

TheravanceSouth San Francisco, CA

cognitive impairment associated with Alzheimer’s disease

Phase I

(RAGE antagonist)

TransTech PharmaHigh Point, NC


UB-311 (amyloid beta protein inhibitor vaccine)

United BiomedicalHauppauge, NY

mild to moderate Alzheimer’s disease Phase I

V950vaccine

MerckWhitehouse Station, NJ


(ACC-001)Janssen Alzheimer ImmunotherapySouth San Francisco, CA

New York, NY


velusetrag TheravanceSouth San Francisco, CA


VI-1121 VIVUSMountain View, CA


XEL 001HP(transdermal patch)

Xel PharmaceuticalsDraper, UT



Glossary

Alzheimer’s disease—The most common form of dementia, characterized by progressive and chronic deterioration of cognitive functions, including memory, thinking and reasoning. Early manifestations include forgetfulness, impaired ability to focus, and changes in mood and personality. As the disease progresses, there is a loss of computational ability, in addi-

ordinary activities. Ultimately, the disease leads to severe memory loss, complete disorienta-tion, social withdrawal, loss of independence, and is fatal.

application submitted—An application for marketing approval has been submitted to the U.S. Food and Drug Administration (FDA). The application can either be an NDA (new drug application) or a BLA (biologic license application).

cognitive disorders—Disorders of the higher mental processes, including understand-ing, reasoning, knowledge, and intellectual capacity. A person with a cognitive disorder, such as Alzheimer’s disease, does not process information correctly within the brain, resulting

reasoning and focusing, loss of memory and abnormal mental capacity. People with cogni-tive disorders have problems acquiring, men-tally organizing and responding to information, which results in an inability to function normally in everyday life situations.

dementia—Loss of mental ability that inter-feres with normal daily activities. It lasts more than six months, it not present at birth and is not associated with loss or altered conscious-ness. The natural decline of these functions with age is grossly exaggerated in dementia.

Fast Track—A U.S. Food and Drug Admin-istration (FDA) process designed to facilitate development and expedite the regulatory

review of drugs to treat serious diseases and

get new drugs for serious diseases to patients earlier and must be requested by the biophar-maceutical company. Fast Track addresses a broad range of serious diseases. Generally, determining factors include whether the drug will have an impact on such factors as survival, day-to-day functioning, or the likelihood that the disease, if left untreated, will progress from a less severe condition to a more serious

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 designation, 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, with the goal to achieve earlier drug approval and access by patients.

mild Alzheimer’s disease—A stage of Al-zheimer’s disease characterized by a series of changes in cognitive abilities that may include,

problem solving, changes in personality, dif-

getting lost or misplacing belongings. This is

diagnosed.

moderate Alzheimer’s disease—A stage of Alzheimer’s disease characterized by increased confusion, greater memory loss, sig-

for assistance with basic daily activities. These changes are related to damage in areas of the brain that control language, reasoning, sensory processing, and conscious thinking. At this stage, patients may have problems recognizing family and friends, experience hallucinations,

delusions, and paranoia, and may behave impulsively.

PET imaging—Positron emission tomography (PET), a noninvasive medical imaging tech-nique that utilizes a radioactive agent (“tracer”) incorporated in a biologically active molecule and a scanner to produce three-dimensional images of the body.

Phase 0—First-in-human trials conducted in accordance with FDA’s 2006 guidance on exploratory Investigational New Drug (IND) studies designed to speed up development of promising drugs by establishing very early on whether the agent behaves in human subjects as was anticipated from preclinical studies.

Phase I—Researchers test the drug in a small

healthy adult volunteers, to evaluate its initial

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

effectiveness. They are the longest studies, and usually take place in multiple sites around the world.

tauopathies—A group of neurodegenerative diseases characterized by accumulation of

include Alzheimer’s disease, Pick’s disease, corticobasal degeneration, and other related disorders.


Selected Facts about Alzheimer’s Disease and Other Dementias

An estimated 5.4 million Americans have Alzheimer’s disease (AD)—the most common form of dementia—including some 200,000 people younger than age 65 who make up the younger-onset AD population.

Some 5.2 million people with Alzheimer’s are age 65 and older;; of these, 3.4 million are women and 1.8 million are men.

AD accounts for 60 percent to 80 percent of all cases of dementias.

In 2010, an estimated 5.1 million Americans age 65 and older had Alzheimer’s disease. That number was expected to increase to 5.6 million in 2020;; 7.8 million by 2030;; and 13.5 million by 2050. By that year, the percentage of people age 65 and older with Alzheimer’s could be as high

AD

decreased by 13 percent, 20 percent, and 8 percent, respectively, whereas the proportion due to AD increased by 66 percent.

In 2009, Alzheimer’s

underlying cause. This increase could be due to reporting changes and an increase in actual Alzheimer’s deaths.

Some 60 percent to 70 percent of people with Alzheimer’s and other dementias live at home, where they are cared for by family and friends.

In 2011, more than 15 million family members and other unpaid caregivers provided an estimated 17.4 billion hours of care to people with AD and other dementias, a contribution valued at more than $210 billion.

More than 70 percent of family and other unpaid caregivers of people with Alzheimer’s disease and other dementias are women.

AD and other dementias are three times as great as payments for

hospice services for people age 65 and older with AD and other dementias are expected to be $200 billion (not including the contributions of unpaid caregivers).

Alzheimer’s Disease/Dementias

Source:

Alzheimer’s Association, 2012 Alzheimer’s Disease Facts and Figures.

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 August 15, 2012. -tact 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

www.phrma.org | www.innovation.org | www.pparx.org | www.buysafedrugs.info

Provided as a Public Service by PhRMA. Founded in 1958 as the Pharmaceutical Manufacturers Association.

Copyright © 2012 by the Pharmaceutical Research and Manufacturers of America. Permission to reprint is awarded if proper credit is given.

950 F Street, NW, Washington, DC 20004

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

compounds that enter preclinical testing make

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.

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

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

conducted. Progress reports on clinical trials

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

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

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). completion of all three phases of clinical trials,

demonstrate both safety and effectiveness.

information that the company has gathered. Applications typically run 100,000 pages or more.Approval.

for physicians to prescribe. A company must

including any cases of adverse reactions and

Discovering and developing safe and effective

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

LZHEIMER ÕS D ISE A SE … · 4 Medicines in Development Alzheimer’s Disease 2012...

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