2012 REPO

Medicines in Development ALZHEIMER’S DISEASE R

PRESENTED BY AMERICA’S BIOPHARMACEUTICAL T RESEARCH COMPANIES

Biopharmaceutical Research Companies are Developing Nearly 100 Medicines for Alzheimer’s Disease and Other Dementias

Medicines in Development For Alzheimer’s Disease*

81

Today, more than 5 million Americans are suf- human clinical trials or awaiting U.S. Food and fering from Alzheimer’s disease. The disease Drug Administration (FDA) review. They are ravages the minds of patients, crushes entire exploring various new approaches to treating families and currently costs the health care Alzheimer’s disease, including: system $200 billion a year. These sobering  ‡$PHGLFLQHWKDWLQKLELWVWKHIRUPDWLRQDQG statistics are projected to get much worse as accumulation of amyloid-beta and tau the 76 million American baby boomers age. protein deposits. If no new medicines are found to prevent,  ‡$QLQWUDQDVDOPHGLFLQHWKDWLVDEOHWR delay or stop the progression of Alzheimer’s penetrate the blood-brain barrier for mild disease, the number of people affected in cognitive impairment, a precursor to America will jump to 13.5 million by 2050, Alzheimer’s. according to the Alzheimer’s Association. Costs for care for Alzheimer’s patients will  ‡$JHQHWKHUDS\IRUWKHWUHDWPHQWRI LQFUHDVH¿YHIROGWRWULOOLRQD\HDU Alzheimer’s disease. Even modest progress can drastically change 7KHTXHVWLVLQWHQVHDQG¿QDQFLDOO\ULVN\,W takes, on average, more than $1 billion and 11 this trajectory. A breakthrough medicine that delays the onset of Alzheimer’s disease by 10 to 15 years to develop a new medicine. But MXVW¿YH\HDUVFRXOGGHFUHDVHWKHQXPEHURI QHZVFLHQWL¿FDGYDQFHVDUHLQFUHDVLQJRXU 5 Americans suffering from the disease in 2050 knowledge, and researchers are using every 2 by 43 percent and the related costs of care by cutting-edge tool at their disposal. With contin- ued dedication, we hope to make a difference $447 billion. Hope for the future lies in medical ’s e s innovation. for every person at risk of suffering from this terrible, debilitating disease. Diseas CognitionDisorder America’s biopharmaceutical companies cur- Alzheimer Dementias Diagnostics rently have 93 medicines in development for * Some medicines are in development Alzheimer’s disease and dementias—either in for more than one disorder. Medicines in Development for Alzheimer’s Disease

ALZHEIMER’S DISEASE AND DEMENTIAS

Product Name Sponsor Indication Development Status*

AAB-002 Janssen Alzheimer Immunotherapy Alzheimer’s disease Phase 0 (amyloid beta-protein inhibitor South San Francisco, CA   mAb) 3¿]HU   New York, NY

$$%3) Janssen Alzheimer Immunotherapy Alzheimer’s disease Phase I (amyloid beta-protein inhibitor South San Francisco, CA   mAb) 3¿]HU   New York, NY

ABT-126 Abbott Laboratories mild to moderate Alzheimer’s disease Phase II (alpha-7 neuronal nicotinic Abbott Park, IL   receptor antagonist) ------Alzheimer’s disease Phase I (combination therapy),   Alzheimer’s disease (elderly)

$%7 Abbott Laboratories Alzheimer’s disease Phase II (neurotransmitter receptor Abbott Park, IL   modulator)

$%7 Abbott Laboratories mild to moderate Alzheimer’s disease Phase II Abbott Park, IL  

ABT-560 Abbott Laboratories cognitive disorders Phase I (alpha-4 beta-2 nicotinic Abbott Park, IL   receptor modulators)

ABT-957 Abbott Laboratories Alzheimer’s disease Phase I (calpain inhibitor) Abbott Park, IL  

ACC-002 Janssen Alzheimer Immunotherapy Alzheimer’s disease Phase 0 (amyloid-beta peptide South San Francisco, CA   conjugate) 3¿]HU   New York, NY

AD02 vaccine $I¿ULV Alzheimer’s disease Phase II Vienna, Austria   GlaxoSmithKline Rsch. Triangle Park, NC

AD03 vaccine $I¿ULV Alzheimer’s disease Phase I Vienna, Austria   GlaxoSmithKline Rsch. Triangle Park, NC

)RUPRUHLQIRUPDWLRQDERXWDVSHFL¿FPHGLFLQHLQWKLVUHSRUWSOHDVHFDOOWKHWHOHSKRQHQXPEHUOLVWHG

2 Medicines in Development Alzheimer’s Disease 2012 Medicines in Development for Alzheimer’s Disease

ALZHEIMER’S DISEASE AND DEMENTIAS

Product Name Sponsor Indication Development Status

$'6 Adamas Pharmaceuticals moderate to severe Alzheimer’s Phase II (donepezil/memantine) Emeryville, CA disease (510) 450-3500

APH-0703 Aphios Alzheimer’s disease, Phase I/II Woburn, MA cognitive disorders  

ARC029 Archer Pharmaceuticals mild to moderate Alzheimer’s disease Phase I (soluble amyloid Sarasota, FL (941) 755-6644 reducing/clearing agent) (Orphan Drug)

ARC031 Archer Pharmaceuticals Alzheimer’s disease Phase I (soluble amyloid Sarasota, FL (941) 755-6644 reducing/clearing agent)

ASP0777 Astellas Pharma US dementia associated with Alzheimer’s Phase I 'HHU¿HOG,/ disease  

AVN 101 Avineuro Pharmaceuticals cognitive enhancer in Alzheimer’s Phase II (serotonin 6 receptor San Diego, CA disease   antagonist)

AVN 322 Avineuro Pharmaceuticals Alzheimer’s disease Phase I (serotonin 6 receptor San Diego, CA   antagonist)

AVN 397 Avineuro Pharmaceuticals Alzheimer’s disease Phase II San Diego, CA  

AZD1446 AstraZeneca Alzheimer’s disease Phase I (alpha4/beta2 neuronal Wilmington, DE   nicotinic receptor agonist) Targacept   Winston-Salem, NC

$=' AstraZeneca Alzheimer’s disease Phase II (ispronicline) Wilmington, DE   Targacept Winston-Salem, NC

AZD4694 Navidea Biopharmaceuticals Alzheimer’s disease (diagnosis) Phase II ÀXRULQHODEHOHGSUHFLVLRQ Dublin, OH (614) 793-7500 radiopharmaceutical)

AZD5213 AstraZeneca Alzheimer’s disease Phase II (histamine-3 receptor Wilmington, DE   antagonist)

Medicines in Development Alzheimer’s Disease 2012 3 Medicines in Development for Alzheimer’s Disease

ALZHEIMER’S DISEASE AND DEMENTIAS

Product Name Sponsor Indication Development Status

ß secretase inhibitor Eli Lilly Alzheimer’s disease Phase II Indianapolis, IN (800) 545-5979

BAN2401 BioArtic Neuroscience mild to moderate Alzheimer’s disease Phase I (amyloid beta-protein inhibitor) Stockholm, Sweden www.bioarti.se Eisai (888) 274-2378 Woodcliff Lake, NJ

bapineuzumab subcutaneous Janssen Alzheimer Immunotherapy Alzheimer’s disease Phase II (AAB-001) South San Francisco, CA (subcutaneous) (888) 381-4595 3¿]HU (800) 879-3477 New York, NY

BCI-632 BrainCells Alzheimer’s disease Phase I San Diego, CA (858) 812-7700

BCI-838 BrainCells Alzheimer’s disease Phase I San Diego, CA (858) 812-7700

BIIB037 Biogen Idec Alzheimer’s disease Phase I (amyloid beta-protein inhibitor) Cambridge, MA (617) 679-2000

bisnorcymserine QR Pharma Alzheimer’s disease Phase I (BNC) Berwyn, PA (610) 727-3913

BMS-241027 Bristol-Myers Squibb Alzheimer’s disease, tauopathies Phase I (microtubule stabilizer) Princeton, NJ (800) 332-2056

BMS-708163 Bristol-Myers Squibb Alzheimer’s disease Phase II (avagacestat) Princeton, NJ (800) 332-2056

BMS-932481 Bristol-Myers Squibb Alzheimer’s disease Phase I (gamma secretase modulator) Princeton, NJ (800) 332-2056

BMS-933043 Bristol-Myers Squibb cognitive impairment Phase I (a-7 nicotinic agonist) Princeton, NJ (800) 332-2056

CAD106 Novartis Pharmaceuticals Alzheimer’s disease Phase II (amyloid beta-protein inhibitor) East Hanover, NJ (888) 669-6682

CERE-110 Ceregene Alzheimer’s disease Phase II (AAV-NGF gene therapy) San Diego, CA (858) 458-8800

CHF-5074 Chiesi Pharmaceuticals mild cognitive impairment Phase II (amyloid precursor protein Rockville, MD (301) 424-2661 secretase modulator)

4 Medicines in Development Alzheimer’s Disease 2012 Medicines in Development for Alzheimer’s Disease

ALZHEIMER’S DISEASE AND DEMENTIAS

Product Name Sponsor Indication Development Status

crenezumab Genentech Alzheimer’s disease Phase II (anti-Abeta) South San Francisco, CA  

CTS-21166 Astellas Pharma US Alzheimer’s disease Phase I (ß-secretase inhibitor) 'HHU¿HOG,/   CoMentis (650) 359-2600 South San Francisco, CA

CX717 Cortex Pharmaceuticals Alzheimer’s disease Phase II completed Irvine, CA (949) 727-3157

davunetide intranasal Allon Therapeutics Alzheimer’s disease, mild cognitive Phase II Vancouver, Canada impairment (604) 736-0634

docosahexaenoic acid Martek Biosciences Alzheimer’s disease Phase III (DHA) Parsippany, NJ  

'63 Sunovion Pharmaceuticals Alzheimer’s disease Phase I (PPAR _/a agonist) Marlborough, MA  

E2212 Eisai Alzheimer’s disease Phase I (amyloid precursor protein Woodcliff Lake, NJ   secretase modulator)

E2609 Eisai Alzheimer’s disease Phase I (BACE1 protein inhibitor) Woodcliff Lake, NJ  

ELND005 Elan mild to moderate Alzheimer’s disease Phase II (amyloid beta-protein inhibitor) South San Francisco, CA (Fast Track)   Transition Therapeutics (416) 260-7770 Toronto, Canada

EVP-0962 EnVivo Pharmaceuticals Alzheimer’s disease Phase I (amyloid precursor protein Watertown, MA (617) 225-4250 secretase modulator)

EVP-6124 EnVivo Pharmaceuticals mild to moderate Alzheimer’s disease Phase II ĮQ$&K5DJRQLVW Watertown, MA (617) 225-4250

Exebryl-1® ProteoTech Alzheimer’s disease Phase I Kirkland, WA  

)ÀRUEHWDEHQ Piramal Healthcare Alzheimer’s disease (diagnosis) Phase III (molecular imaging agent) Mumbai, India www.piramalhealthcare.com

)ÀXWHPHWDPRO GE Healthcare Alzheimer’s disease (diagnosis) Phase III (PET imaging agent) Waukesha, WI www.gehealthcare.com

Medicines in Development Alzheimer’s Disease 2012 5 Medicines in Development for Alzheimer’s Disease

ALZHEIMER’S DISEASE AND DEMENTIAS

Product Name Sponsor Indication Development Status

Gammagard® Baxter Healthcare early-stage Alzheimer’s disease, Phase III immune globulin intravenous 'HHU¿HOG,/ mid-stage Alzheimer’s disease   (human), 10% solution

gantenerumab Roche prodromal Alzheimer’s disease Phase II/III (RG1450) Nutley, NJ (973) 235-5000

GSK239512 GlaxoSmithKline Alzheimer’s disease Phase II completed Rsch. Triangle Park, NC  

GSK742457 GlaxoSmithKline Alzheimer’s disease Phase II completed (5HT6 antagonist) Rsch. Triangle Park, NC  

GSK933776A GlaxoSmithKline Alzheimer’s disease Phase I completed (anti-B amyloid mAb) Rsch. Triangle Park, NC  

+33 High Point Pharmaceuticals Alzheimer’s disease Phase I (BACE1 inhibitor) High Point, NC  

human immunoglobulin Grifols USA Alzheimer’s disease Phase III (intravenous) Los Angeles, CA  

immune globulin high dose Octapharma USA Alzheimer’s disease (elderly) Phase II completed Hoboken, NJ (201) 604-1130

irdabisant Cephalon cognitive dysfunction associated with Phase I (CEP-26401) Frazer, PA Alzheimer’s disease (610) 344-0200

LMTX TauRx Pharmaceuticals mild to moderate Alzheimer’s disease Phase I (TRx-0237) Singapore www.taurx.com

LNK-754 Link Medicine mild Alzheimer’s disease Phase I completed Waltham, MA  

/8$( Lundbeck Alzheimer’s disease Phase II 'HHU¿HOG,/  

0&'JO\FRS\UURODWH Mithridion autosomal dominant Alzheimer’s Phase I Madison, WI disease www.mithridion.com

MK-3134 Merck dementia Phase I completed Whitehouse Station, NJ  

0. Merck Alzheimer’s disease (diagnosis) Phase I completed (PET tracer) Whitehouse Station, NJ  

0. Merck Alzheimer’s disease Phase I (BACE1 inhibitor) Whitehouse Station, NJ  

6 Medicines in Development Alzheimer’s Disease 2012 Medicines in Development for Alzheimer’s Disease

ALZHEIMER’S DISEASE AND DEMENTIAS

Product Name Sponsor Indication Development Status

MSDC-0160 Metabolic Solutions Development Alzheimer’s disease Phase II Company (269) 343-6732 Kalamazoo, MI

NIC5-15 Humanetics Alzheimer’s disease Phase II Minneapolis, MN (952) 937-7660

PF-05212377 3¿]HU Alzheimer’s disease Phase I (SAM-760) New York, NY  

pioglitazone Takeda Pharmaceuticals U.S.A. Alzheimer’s disease (diagnosis) Phase I companion 'HHU¿HOG,/   diagnostic Zinfadel Pharmaceuticals Chapel Hill, NC

Posiphen™ QR Pharma Alzheimer’s disease, Phase II R-phenserine Berwyn, PA mild cognitive impairment (610) 727-3913

PRX-3140 Nanotherapeutics Alzheimer’s disease Phase II (5-HT4 partial agonist) Alachua, FL  

RG1577 Roche Alzheimer’s disease Phase II (MAO-B inhibitor) Nutley, NJ (973) 235-5000

RG1662 Roche cognitive disorders Phase I

(GABAA a5 receptor modulator) Nutley, NJ (973) 235-5000

RG7129 Roche Alzheimer’s disease Phase I (BACE1 protein inhibitor) Nutley, NJ (973) 235-5000

rilapladib GlaxoSmithKline Alzheimer’s disease Phase II Rsch. Triangle Park, NC   Human Genome Sciences   Rockville, MD

59; Resverlogix Alzheimer’s disease Phase I (BET protein inhibitor) Calgary, Canada (403) 254-9252

6$5 6DQR¿86 Alzheimer’s disease Phase II (H3 antagonist) Bridgewater, NJ  

6$5 6DQR¿86 Alzheimer’s disease Phase I Bridgewater, NJ  

sGC-1061 sGC Pharma Alzheimer’s disease Phase I Wellesley, MA (613) 791-4464

Medicines in Development Alzheimer’s Disease 2012 7 Medicines in Development for Alzheimer’s Disease

ALZHEIMER’S DISEASE AND DEMENTIAS

Product Name Sponsor Indication Development Status

solanezumab Eli Lilly Alzheimer’s disease Phase III Indianapolis, IN  

ST-101 Sonexa Therapeutics Alzheimer’s disease Phase II San Diego, CA  

SYN-120 Biotie Therapies cognitive disorders associated with Phase I completed South San Francisco, CA Alzheimer’s disease  

70$ Toyama Chemical mild to moderate Alzheimer’s disease Phase II completed Tokyo, Japan www.toyama-chemical.co.jp

TC-5619 Targacept Alzheimer’s disease Phase I Winston-Salem, NC  

7' Theravance cognitive impairment associated with Phase I (5-HT4 agonist) South San Francisco, CA Alzheimer’s disease  

773 TransTech Pharma Alzheimer’s disease Phase II (RAGE antagonist) High Point, NC  

UB-311 United Biomedical mild to moderate Alzheimer’s disease Phase I (amyloid beta protein inhibitor Hauppauge, NY   vaccine)

V950 Merck Alzheimer’s disease Phase I vaccine Whitehouse Station, NJ  

YDQXWLGHFULGL¿FDU Janssen Alzheimer Immunotherapy Alzheimer’s disease Phase II (ACC-001) South San Francisco, CA   3¿]HU   New York, NY

velusetrag Theravance Alzheimer’s disease Phase I 7' South San Francisco, CA  

VI-1121 VIVUS Alzheimer’s disease Phase II Mountain View, CA (650) 934-5200

XEL 001HP Xel Pharmaceuticals Alzheimer’s disease Phase I (transdermal patch) Draper, UT  

8 Medicines in Development Alzheimer’s Disease 2012 Glossary

Alzheimer’s disease—The most common review of drugs to treat serious diseases and delusions, and paranoia, and may behave form of dementia, characterized by progressive ¿OODQXQPHWPHGLFDOQHHG7KHSXUSRVHLVWR impulsively. and chronic deterioration of cognitive functions, get new drugs for serious diseases to patients including memory, thinking and reasoning. earlier and must be requested by the biophar- PET imaging—Positron emission tomography Early manifestations include forgetfulness, maceutical company. Fast Track addresses a (PET), a noninvasive medical imaging tech- impaired ability to focus, and changes in mood broad range of serious diseases. Generally, nique that utilizes a radioactive agent (“tracer”) and personality. As the disease progresses, determining factors include whether the drug incorporated in a biologically active molecule there is a loss of computational ability, in addi- will have an impact on such factors as survival, and a scanner to produce three-dimensional WLRQWRZRUG¿QGLQJSUREOHPVDQGGLI¿FXOW\ZLWK day-to-day functioning, or the likelihood that images of the body. ordinary activities. Ultimately, the disease leads the disease, if left untreated, will progress Phase 0—First-in-human trials conducted to severe memory loss, complete disorienta- from a less severe condition to a more serious in accordance with FDA’s 2006 guidance on tion, social withdrawal, loss of independence, RQH)LOOLQJDQXQPHWPHGLFDOQHHGLVGH¿QHG exploratory Investigational New Drug (IND) and is fatal. as providing a therapy where none exists or studies designed to speed up development of providing a therapy which may be potentially promising drugs by establishing very early on application submitted—An application for superior to existing therapy. Once a drug marketing approval has been submitted to the whether the agent behaves in human subjects receives Fast Track designation, early and as was anticipated from preclinical studies. U.S. Food and Drug Administration (FDA). frequent communication between the FDA and The application can either be an NDA (new a drug company is encouraged throughout the Phase I—Researchers test the drug in a small drug application) or a BLA (biologic license entire drug development and review process. JURXSRISHRSOHXVXDOO\EHWZHHQDQG application). The frequency of communication assures that healthy adult volunteers, to evaluate its initial cognitive disorders—Disorders of the higher questions and issues are resolved quickly, with VDIHW\DQGWROHUDELOLW\SUR¿OHGHWHUPLQHD mental processes, including understand- the goal to achieve earlier drug approval and safe dosage range, and identify potential side ing, reasoning, knowledge, and intellectual access by patients. effects. capacity. A person with a cognitive disorder, mild Alzheimer’s disease—A stage of Al- Phase II—The drug is given to volunteer such as Alzheimer’s disease, does not process zheimer’s disease characterized by a series of patients, usually between 100 and 300, to see information correctly within the brain, resulting changes in cognitive abilities that may include, if it is effective, identify an optimal dose, and to LQLPSDLUHGDZDUHQHVVDQGMXGJPHQWGLI¿FXOW\ PHPRU\ORVVIRUUHFHQWHYHQWVGLI¿FXOW\ZLWK further evaluate its short-term safety. reasoning and focusing, loss of memory and problem solving, changes in personality, dif- abnormal mental capacity. People with cogni- ¿FXOW\RUJDQL]LQJDQGH[SUHVVLQJWKRXJKWV Phase III—The drug is given to a larger, more tive disorders have problems acquiring, men- getting lost or misplacing belongings. This is diverse patient population, often involving be- tally organizing and responding to information, WKHVWDJHDWZKLFKWKHGLVHDVHLVRIWHQ¿UVW tween 1,000 and 3,000 patients (but sometime which results in an inability to function normally diagnosed. many more thousands), to generate statistically in everyday life situations. VLJQL¿FDQWHYLGHQFHWRFRQ¿UPLWVVDIHW\DQG moderate Alzheimer’s disease—A stage effectiveness. They are the longest studies, dementia—Loss of mental ability that inter- of Alzheimer’s disease characterized by and usually take place in multiple sites around feres with normal daily activities. It lasts more increased confusion, greater memory loss, sig- the world. than six months, it not present at birth and is QL¿FDQWFKDQJHVLQSHUVRQDOLW\DQGWKHQHHG not associated with loss or altered conscious- for assistance with basic daily activities. These tauopathies—A group of neurodegenerative ness. The natural decline of these functions changes are related to damage in areas of the diseases characterized by accumulation of with age is grossly exaggerated in dementia. brain that control language, reasoning, sensory WDX IJ SURWHLQLQWKHEUDLQ7KRVHGLVHDVHV include Alzheimer’s disease, Pick’s disease, Fast Track—A U.S. Food and Drug Admin- processing, and conscious thinking. At this stage, patients may have problems recognizing corticobasal degeneration, and other related istration (FDA) process designed to facilitate disorders. development and expedite the regulatory family and friends, experience hallucinations,

Medicines in Development Alzheimer’s Disease 2012 9 Selected Facts about Alzheimer’s Disease and Other Dementias

Alzheimer’s Disease/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 DVSHUFHQWXQOHVVUHVHDUFKHUV¿QGDZD\WRSUHYHQWRUWUHDWWKHGLVHDVH

‡ AD LVWKHVL[WKOHDGLQJFDXVHRIGHDWKLQWKH8QLWHG6WDWHVDQGWKH¿IWKOHDGLQJFDXVHRIGHDWKLQ$PHULFDQVDJHDQGROGHU7KHSURSRUWLRQ RIGHDWKVGXHWR$'KDVULVHQVLJQL¿FDQWO\%HWZHHQDQGWKHSURSRUWLRQRIGHDWKVGXHWRKHDUWGLVHDVHVWURNHDQGSURVWDWHFDQFHU decreased by 13 percent, 20 percent, and 8 percent, respectively, whereas the proportion due to AD increased by 66 percent.

‡ In 2009, Alzheimer’sZDVOLVWHGDVWKHFDXVHRIGHDWKIRU$PHULFDQV,QRQO\GHDWKFHUWL¿FDWHVUHFRUGHG$O]KHLPHU¶VDVWKH 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. ‡0HGLFDUHSD\PHQWVIRUVHUYLFHVWREHQH¿FLDULHVDJHDQGROGHUZLWKAD and other dementias are three times as great as payments for EHQH¿FLDULHVZLWKRXWWKRVHFRQGLWLRQVDQG0HGLFDLGSD\PHQWVDUHWLPHVDVJUHDW,QSD\PHQWVIRUKHDOWKFDUHORQJWHUPFDUHDQG 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).

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. 7KHLQIRUPDWLRQPD\QRWEHFRPSUHKHQVLYH)RUPRUHVSHFL¿FLQIRUPDWLRQDERXWDSDUWLFXODUSURGXFWFRQ- 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.

3KDUPDFHXWLFDO5HVHDUFKDQG0DQXIDFWXUHUVRI$PHULFD‡950 F Street, NW, Washington, DC 20004

10 Medicines in Development Alzheimer’s Disease 2012 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 The U.S. system of new drug approvals is LQSHRSOH7KH,1'VKRZVUHVXOWVRISUHYLRXV VWDWLVWLFDOO\VLJQL¿FDQWHYLGHQFHWRFRQ¿UPLWV perhaps the most rigorous in the world. experiments; how, where and by whom the safety and effectiveness. They are the longest new studies will be conducted; the chemical studies, and usually take place in multiple sites It takes 10-15 years, on average, for an structure of the compound; how it is thought around the world. experimental drug to travel from lab to U.S. to work in the body; any toxic effects found in patients, according to the Tufts Center for the New Drug Application (NDA)/Biologic the animal studies; and how the compound 6WXG\RI'UXJ'HYHORSPHQW2QO\¿YHLQ License Application (BLA). )ROORZLQJWKH is manufactured. All clinical trials must be compounds that enter preclinical testing make completion of all three phases of clinical trials, reviewed and approved by the Institutional LWWRKXPDQWHVWLQJ$QGRQO\RQHRIWKRVH¿YH DFRPSDQ\DQDO\]HVDOORIWKHGDWDDQG¿OHVDQ 5HYLHZ%RDUG ,5% ZKHUHWKHWULDOVZLOOEH is approved for sale. 1'$RU%/$ZLWK)'$LIWKHGDWDVXFFHVVIXOO\ conducted. Progress reports on clinical trials demonstrate both safety and effectiveness. On average, it costs a company $1.2 billion, PXVWEHVXEPLWWHGDWOHDVWDQQXDOO\WR)'$DQG 7KHDSSOLFDWLRQVFRQWDLQDOORIWKHVFLHQWL¿F including the cost of failures, to get one new the IRB. information that the company has gathered. medicine from the laboratory to U.S. patients, Clinical Trials, Phase I—Researchers test Applications typically run 100,000 pages or according to a 2007 study by the Tufts Center the drug in a small group of people, usually more. for the Study of Drug Development. between 20 and 80 healthy adult volunteers, to Approval. 2QFH)'$DSSURYHVDQ1'$RU 2QFHDQHZFRPSRXQGKDVEHHQLGHQWL¿HGLQ HYDOXDWHLWVLQLWLDOVDIHW\DQGWROHUDELOLW\SUR¿OH %/$WKHQHZPHGLFLQHEHFRPHVDYDLODEOH the laboratory, medicines are usually devel- determine a safe dosage range, and identify for physicians to prescribe. A company must oped as follows: potential side effects. FRQWLQXHWRVXEPLWSHULRGLFUHSRUWVWR)'$ Preclinical Testing. A pharmaceutical com- Clinical Trials, Phase II—The drug is given including any cases of adverse reactions and pany conducts laboratory and animal studies to volunteer patients, usually between 100 and DSSURSULDWHTXDOLW\FRQWUROUHFRUGV)RUVRPH to show biological activity of the compound 300, to see if it iseffective, identify an optimal PHGLFLQHV)'$UHTXLUHVDGGLWLRQDOWULDOV against the targeted disease, and the com- dose, and to further evaluate its short-term 3KDVH,9 WRHYDOXDWHORQJWHUPHIIHFWV pound is evaluated for safety. safety. Discovering and developing safe and effective Investigational New Drug Application (IND). Clinical Trials, Phase III—The drug is given to QHZPHGLFLQHVLVDORQJGLI¿FXOWDQGH[SHQVLYH After completing preclinical testing, a company a larger, more diverse patient population, often process. PhRMA member companies invested ¿OHVDQ,1'ZLWKWKH86)RRGDQG'UXJ involving between 1,000 and 3,000 patients (but an estimated $49.5 billion in research and $GPLQLVWUDWLRQ )'$ WREHJLQWRWHVWWKHGUXJ VRPHWLPHPDQ\PRUHWKRXVDQGV WRJHQHUDWH development in 2011.