201R0eport M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses P R E S E N T E D B Y A M E R I C A ’ S P H A R M A C E U T I C A L R E S E A R C H C O M P A N I E S Pharmaceutical Research Companies Are Developing More Than 300 Medicines to Treat Mental Illnesses

merica’s pharmaceutical research and biotech- M E D I C I N E S I N D E V E L O P M E N T F O R M E N T A L nology companies are currently developing 313 I L L N E S S E S * Amedicines to help the nearly 60 million American adults today suffering from some form of mental illness— Addictive Disorders 33 from Alzheimer’s disease to depression and from Anxiety Disorders 38 schizophrenia to addictive disorders, such as dependence Attention-Deficit/ 20 on alcohol or drugs. All of the medicines are either in Hyperactivity Disorder Dementias 90 clinical trials or awaiting review by the Food and Drug Depression 71 Administration. Developmental Disorders 6 Over the past half century, pharmaceutical research has Eating Disorders 33 helped transform mental illnesses from misunderstood Personality Disorders 2 causes of shame and fear into often highly treatable con- ditions. For example, medicines for treating depression are Premenstrual Disorders 2 helping thousands of people suffering from this disease live Schizophrenia 54 productive lives. Breakthrough schizophrenia medicines Sleep Disorders 21 enable most patients to be treated in the community rather Other 3 than institutional settings, and medicines for Alzheimer’s * Some medicines are in development for more than one disorder. disease are helping elderly people maintain their inde- pendence longer. Examples of some medicines now being tested to treat Despite such progress, mental illnesses continue to mental illnesses include: exact a heavy human and economic toll. The National • A medicine to potentially treat the varied symptoms Institute of Mental Health (NIMH) estimates that 1 in 4 associated with schizophrenia, with diminished side American adults suffer from a diagnosable mental disor- effects common with current treatments. der. According to the World Health Organization, more than 300 million people worldwide suffer from a mental • A medicine designed to remove beta amyloid protein health disorder. Mental illness, including suicide, accounts from the brain and prevent or reverse progression of for more than 15 percent of the burden of disease in Alzheimer’s disease. established market economies, which is more than the Researching and developing new medicines remains a disease burden caused by all cancers. According to a risky investment and lengthy process—costing, on average, study funded by the NIMH, serious mental illnesses cost $1.3 billion and taking between 10 and 15 years to the United States more than $317 billion annually in lost bring a new medicine to patients. But advances in our wages, health care expenditures and disability benefits. understanding of mental illnesses and how to treat them New medicines today in the research and development have allowed America’s pharmaceutical research and pipeline offer hope of reducing the human and economic biotechnology companies to conduct the cutting-edge costs of mental illnesses. They include: 71 for depression research needed to reduce the destructive toll of these (mood disorders), which affects nearly 21 million Americans; disorders and to allow more patients to lead healthier, 33 for addictive disorders, including dependence on happier, more productive lives. alcohol, tobacco or illicit drugs; 38 medicines for anxiety disorders, which affect more than 40 million adults ages 18 and older; 90 for dementias, including Alzheimer’s disease, which affects more than 5 million Americans; and 54 for schizophrenia, which strikes some 2.4 million David E. Wheadon, M.D. American adults each year. Other potential medicines Senior Vice President, target attention-deficit/hyperactivity disorder, autism, Scientific & Regulatory Affairs eating disorders, personality disorders, premenstrual PhRMA disorders and sleep disorders. Medicines in Development for Mental Illnesses A D D I C T I V E D I S O R D E R S Product Name Sponsor Indication Development Status* 468816 GlaxoSmithKline nicotine dependence Phase II Rsch. Triangle Park, NC (888) 825-5249 618334 GlaxoSmithKline drug dependence Phase I Rsch. Triangle Park, NC (888) 825-5249 AFQ056 Novartis Pharmaceuticals smoking withdrawal Phase I completed East Hanover, NJ (see also developmental disorders) (888) 669-6682 alcohol Eli Lilly alcohol dependence Phase I dependence Indianapolis, IN (800) 545-5979 therapy alcohol Eli Lilly alcohol dependence Phase I dependence Indianapolis, IN (800) 545-5979 therapy ALKS 29 Alkermes alcohol dependence Phase I/II (baclofen/ALKS 33 Cambridge, MA (617) 494-0171 combination) ALKS 33 Alkermes alcohol dependence Phase II Cambridge, MA (617) 494-0171 ------drug dependence, Phase I impulse control disorder (617) 494-0171 ARD-1600 Aradigm nicotine dependence Phase I (nicotine Hayward, CA (510) 265-9000 inhalation) CPP-109 Catalyst Pharmaceutical cocaine dependence Phase II (vigabatrin) Coral Gables, FL (Fast Track) (305) 529-2522 DOV-102677 DOV Pharmaceutical alcohol dependence Phase I Little Falls, NJ (732) 907-3600 EMB-001 Embera NeuroTherapeutics cocaine dependence Phase I completed Shreveport, LA (318) 213-0198 KRL-901 Krele Pharmaceuticals alcohol dependence in clinical trials Saddle River, NJ (212) 923-3400 lobeline Yaupon Therapeutics methamphetamine dependence Phase II Radnor, PA (see also ADHD) (610) 975-9290 lofexidine US WorldMeds opioid dependence Phase III Louisville, KY (502) 753-2094 MK-0594 Merck alcohol dependence Phase II Whitehouse Station, NJ (800) 672-6372 MS-166 MediciNova opioid dependence Phase II San Diego, CA (858) 373-1500

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

2 M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 A D D I C T I V E D I S O R D E R S Product Name Sponsor Indication Development Status nalmefene Lundbeck alcohol dependence Phase III Deerfield, IL (800) 455-1141 ------nicotine dependence Phase II (800) 455-1141 Namenda® Forest Laboratories impulse control disorder Phase II memantine New York, NY (compulsive gambling) (800) 947-5227 NanoBUP™ Nanotherapeutics opioid dependence Phase I completed buprenorphine/ Alachua, FL (386) 462-9663 naloxone neboglamine Rottapharm | Madaus cocaine dependence Phase II (CR 2249) Monza, Italy www.rotta.com NIC 002 Novartis Pharmaceuticals nicotine dependence Phase II East Hanover, NJ (888) 669-6682 NicVAX™ GlaxoSmithKline nicotine dependence Phase III nicotine abuse Rsch. Triangle Park, NC (Fast Track) (888) 825-5249 vaccine Nabi Biopharmaceuticals Boca Raton, FL OpRA Eli Lilly alcohol dependence Phase II Indianapolis, IN (800) 545-5979 Probuphine® Titan Pharmaceuticals opioid dependence Phase III bupenorphine South San Francisco, CA (650) 244-4990 Risperdal® Consta® Johnson & Johnson methamphetamine dependence Phase II risperidone Pharmaceutical Research (see also schizophrenia) (800) 817-5286 (injectable) & Development Raritan, NJ SCH 900435 Merck alcohol dependence Phase II Whitehouse Station, NJ (prevention of relapse) (800) 672-6372 (see also schizophrenia) Seroquel XR® AstraZeneca alcohol dependence Phase II completed quetiapine Wilmington, DE (see also anxiety disorders, (800) 236-9933 fumarate depression, personality disorders) extended-release SYN-117 Roche drug dependence Phase I/II Nutley, NJ (see also anxiety disorders) (973) 235-5000 Synosia Therapeutics (650) 244-4850 South San Francisco, CA TA-CD Celtic Pharma cocaine dependence Phase II (cocaine abuse Hamilton, Bermuda www.celticpharma.com vaccine) TO-2060 Transcept Pharmaceuticals alcohol dependence Phase I (olanzepine/ Pt. Richmond, CA (510) 215-3500 ondansetron) Topamax® Johnson & Johnson alcohol dependence Phase II topiramate Pharmaceutical Research (see also anxiety disorders) (800) 817-5286 & Development Raritan, NJ

M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 3 A D D I C T I V E D I S O R D E R S Product Name Sponsor Indication Development Status vigabatrin Lundbeck cocaine dependence Phase II Deerfield, IL (Fast Track) (847) 282-1000 ------methamphetamine dependence Phase I (847) 282-1000 Vivitrol® Alkermes opioid dependence application submitted naltrexone Cambridge, MA (617) 494-0171 controlled-release

A N X I E T Y D I S O R D E R S Product Name Sponsor Indication Development Status 163090 GlaxoSmithKline anxiety Phase I Rsch. Triangle Park, NC (see also depression) (888) 825-5249 356278 GlaxoSmithKline anxiety Phase I Rsch. Triangle Park, NC (see also depression) (888) 825-5249 424887 GlaxoSmithKline anxiety Phase I Rsch. Triangle Park, NC (see also depression) (888) 825-5249 586529 GlaxoSmithKline anxiety Phase I Rsch. Triangle Park, NC (see also depression) (888) 825-5249 Neurocrine Biosciences (858) 617-7600 San Diego, CA 588045 GlaxoSmithKline anxiety Phase I Rsch. Triangle Park, NC (see also depression) (888) 825-5249 ABT-436 Abbott Laboratories anxiety Phase I Abbott Park, IL (see also depression) (847) 937-6100 ADX71149 Johnson & Johnson anxiety Phase I Pharmaceutical Research (see also schizophrenia) (800) 817-5286 & Development Raritan, NJ AVN101 Avineuro Pharmaceuticals anxiety Phase II San Diego, CA (see also dementias) (858) 436-1537 AVN397 Avineuro Pharmaceuticals anxiety Phase II San Diego, CA (see also dementias) (858) 436-1537 AZD2327 AstraZeneca anxiety Phase II Wilmington, DE (see also depression) (800) 236-9933 AZD6280 AstraZeneca anxiety Phase I Wilmington, DE (800) 236-9933 BCI-540 BrainCells anxiety Phase II San Diego, CA (see also depression) (858) 812-7700 emicerfont GlaxoSmithKline anxiety Phase II Rsch. Triangle Park, NC (see also depression) (888) 825-5249 Neurocrine Biosciences (858) 617-7600 San Diego, CA

4 M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 A N X I E T Y D I S O R D E R S Product Name Sponsor Indication Development Status KRL-104 Krele Pharmaceuticals generalized anxiety disorder in clinical trials Saddle River, NJ (212) 923-3400 Lexapro® Forest Laboratories panic disorder, social phobia application submitted escitalopram New York, NY (800) 947-5227 Lu AA21004 Lundbeck generalized anxiety disorder Phase III Deerfield, IL (see also depression) (800) 455-1141 Lu AA24530 Lundbeck generalized anxiety disorder Phase I Deerfield, IL (see also depression) (800) 455-1141 Lunesta® Sepracor generalized anxiety disorder Phase II eszopiclone Marlborough, MA (see also sleep disorders) (508) 481-6700 Lyrica® Pfizer generalized anxiety disorder application submitted pregbalin New York, NY (860) 732-5156 MDMA Multidisciplinary post-traumatic stress disorder Phase I Association for (831) 421-6362 Psychedelic Studies Santa Cruz, CA NSD-721 GlaxoSmithKline social anxiety disorder Phase I Rsch. Triangle Park, NC (888) 825-5249 NeuroSearch Ballerup, Denmark NSD-788 GlaxoSmithKline anxiety Phase I Rsch. Triangle Park, NC (see also depression) (888) 825-5249 NeuroSearch Ballerup, Denmark orvepitant GlaxoSmithKline post-traumatic stress disorder Phase II Rsch. Triangle Park, NC (see also depression) (888) 825-5249 PH94B Pherin Pharmaceuticals acute anxiety disorder Phase II Redwood City, CA (650) 568-1587 Seroquel XR® AstraZeneca generalized anxiety disorders application submitted quetiapine Wilmington, DE (see also addictive disorders, (800) 236-9933 fumarate depression, personality disorders) extended-release SPN 805 Supernus Pharmaceuticals anxiety Phase I Rockville, MD (301) 838-2500 SPN 808 Supernus Pharmaceuticals anxiety Phase I Rockville, MD (301) 838-2500 SRX 246 Azevan Pharmaceuticals traumatic stress disorders Phase I Bethlehem, PA (610) 419-1057 SSR125543 sanofi-aventis post-traumatic stress disorder Phase I Bridgewater, NJ (see also depression) (800) 633-1610 Strattera® Eli Lilly social phobia Phase II/III atomoxetine Indianapolis, IN (800) 545-5979 SYN-117 Roche post-traumatic stress disorder Phase II Nutley, NJ (see also addictive disorders) (973) 235-5000 Synosia Therapeutics (650) 244-4850 South San Francisco, CA

M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 5 A N X I E T Y D I S O R D E R S Product Name Sponsor Indication Development Status TGWOOAA Fabre-Kramer generalized anxiety disorder, Phase II Pharmaceuticals social phobia (713) 975-6900 Houston, TX TIK-101 Tikvah Therapeutics obsessive-compulsive disorder, Phase II (cycloserine) Atlanta, GA panic disorder, phobic disorders, (404) 920-3180 post-traumatic stress disorder, social phobia Topamax® Johnson & Johnson post-traumatic stress disorder in clinical trials topiramate Pharmaceutical Research (see also addictive disorders) (800) 817-5286 & Development Raritan, NJ TriRima™ CeNeRx BioPharma anxiety Phase I (CX157) Rsch. Triangle Park, NC (see also depression) (919) 234-4650 verucerfont GlaxoSmithKline post-traumatic stress disorder, Phase II Rsch. Triangle Park, NC social phobia (888) 825-5249 Neurocrine Biosciences (see also depression) (858) 617-7600 San Diego, CA YKP-3089 SK Drug Development anxiety Phase II Center (973) 227-3939 Fairfield, NJ Zoloft® Pfizer generalized anxiety disorder in clinical trials sertraline New York, NY (see also eating disorders) (860) 732-5156

A T T E N T I O N - D E F I C I T / H Y P E R A C T I V I T Y D I S O R D E R Product Name Sponsor Indication Development Status amfetamine Noven Pharmaceuticals attention-deficit/hyperactivity Phase I transdermal Miami, FL disorder (ADHD) (305) 253-5099 AZD1446 AstraZeneca ADHD Phase II (TC-6683) Wilmington, DE (see also dementias) (800) 236-9933 Targacept (336) 480-2100 Winston-Salem, NC AZD3480 AstraZeneca ADHD Phase II (TC-1734) Wilmington, DE (800) 236-9933 Targacept (336) 480-2100 Winston-Salem, NC Clonicel® Shionogi Pharma ADHD in adolescents and application submitted clonidine Atlanta, GA children (800) 461-3696 (controlled release) Daytrana® Shire ADHD in adolescents application submitted methylphenidate Wayne, PA (800) 828-2088 transdermal system ------ADHD in adults Phase III (800) 828-2088 droxidopa Chelsea Therapeutics ADHD Phase II Charlotte, NC (combination therapy) (704) 341-1516

6 M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 A T T E N T I O N - D E F I C I T / H Y P E R A C T I V I T Y D I S O R D E R Product Name Sponsor Indication Development Status Intuniv™ Shire ADHD in adolescents and children application submitted guanfacine Wayne, PA (adjunctive treatment, combination (484) 595-8800 (extended release) therapy) JNJ-31001074 Johnson & Johnson ADHD Phase II Pharmaceutical Research (800) 817-5286 & Development ------Raritan, NJ ADHD in children and adolescents Phase I (800) 817-5286 KP106 KemPharm ADHD Phase I North Liberty, IA (319) 665-2575 KRL-401 Krele Pharmaceuticals ADHD in clinical trials Saddle River, NJ (212) 923-3400 lobeline Yaupon Therapeutics ADHD in adults Phase II Radnor, PA (see also addictive disorders) (610) 975-9209 NERI Eli Lilly ADHD Phase II/III (LY2216684) Indianapolis, IN (pediatric patients) (800) 545-5979 (see also depression) OPC-34712 Otsuka America ADHD Phase II Pharmaceutical (adjunctive treatment) (800) 562-3974 Rockville, MD (see also depression, schizophrenia) SEP-228432 Sepracor ADHD Phase I/II Marlborough, MA (508) 481-6700 sofinicline Abbott Laboratories ADHD Phase II Abbott Park, IL (847) 937-6100 SPN 810 Supernus Pharmaceuticals ADHD in children Phase II completed Rockville, MD (301) 838-2500 SPN 811 Supernus Pharmaceuticals ADHD Phase I Rockville, MD (301) 838-2500 SPN 812V Supernus Pharmaceuticals ADHD Phase I/II Rockville, MD (301) 838-2500 TC5619 AstraZeneca ADHD Phase II Wilmington, DE (see also dementias) (800) 236-9933 Targacept Winston-Salem, NC Vyvanse® Shire ADHD in adolescents Phase III lisdexamfetamine Wayne, PA (see also depression, schizophrenia, (800) 828-2088 dimesylate sleep disorders)

D E M E N T I A S Product Name Sponsor Indication Development Status Diseases in this category are medical conditions involving the brain and can also be categorized as neurological disorders. 18-flutemetamol GE Healthcare Alzheimer’s disease diagnosis Phase III (PET imaging agent) Waukesha, WI www.gehealthcare.com

M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 7 D E M E N T I A S Product Name Sponsor Indication Development Status 239512 GlaxoSmithKline Alzheimer’s disease Phase II Rsch. Triangle Park, NC (see also schizophrenia) (888) 825-5249 ------mild cognitive impairment Phase I completed (888) 825-5249 742457 GlaxoSmithKline Alzheimer’s disease Phase II Rsch. Triangle Park, NC (888) 825-5249 933776A GlaxoSmithKline Alzheimer’s disease Phase I Rsch. Triangle Park, NC (888) 825-5249 1034702 GlaxoSmithKline dementia Phase I Rsch. Triangle Park, NC (see also schizophrenia) (888) 825-5249 AAB-002 Janssen Alzheimer Alzheimer’s disease Phase 0 Immunotherapy (800) 817-5286 South San Francisco, CA (860) 732-5156 Pfizer New York, NY AAB-003 Janssen Alzheimer Alzheimer’s disease Phase 0 Immunotherapy (800) 817-5286 South San Francisco, CA (860) 732-5156 Pfizer New York, NY ABT-126 Abbott Laboratories Alzheimer’s disease Phase II Abbott Park, IL (see also schizophrenia) (847) 937-6100 ------Alzheimer’s disease in the elderly Phase I (847) 937-6100 ABT-288 Abbott Laboratories Alzheimer’s disease Phase II Abbott Park, IL (see also schizophrenia) (847) 937-6100 ABT-384 Abbott Laboratories Alzheimer’s disease Phase II Abbott Park, IL (847) 937-6100 ABT-560 Abbott Laboratories cognition disorders Phase I Abbott Park, IL (847) 937-6100 ACC-002 Janssen Alzheimer Alzheimer’s disease Phase 0 Immunotherapy (800) 817-5286 South San Francisco, CA (860) 732-5156 Pfizer New York, NY AD02 Affiris Alzheimer’s disease Phase II vaccine Vienna, Austria (888) 825-5249 GlaxoSmithKline Rsch. Triangle Park, NC ADS-8703 Adamas Pharmaceuticals dementia Phase II Emeryville, CA (510) 450-3500 Alzheimer’s Eli Lilly agitation in Alzheimer’s disease Phase II therapy Indianapolis, IN (800) 545-5979 AMG 747 Amgen cognition disorders associated Phase I Thousand Oaks, CA with schizophrenia (805) 447-1000

8 M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 D E M E N T I A S Product Name Sponsor Indication Development Status ARC029 Archer Pharmaceuticals Alzheimer’s disease Phase I Sarasota, FL (941) 755-6644 ARC031 Archer Pharmaceuticals Alzheimer’s disease Phase I Sarasota, FL (941) 755-6644 ASP 0777 Astellas Pharma US Alzheimer’s disease Phase I Deerfield, IL (800) 695-4321 AV965 Avera Pharmaceuticals Alzheimer’s disease, Phase I San Diego, CA cognition disorders (858) 847-0650 AVN 101 Avineuro Pharmaceuticals Alzheimer’s disease Phase II San Diego, CA (see also anxiety disorders) (858) 436-1537 AVN 322 Avineuro Pharmaceuticals Alzheimer’s disease Phase I San Diego, CA (858) 436-1537 AVN 397 Avineuro Pharmaceuticals Alzheimer’s disease Phase II San Diego, CA (see also anxiety disorders) (858) 436-1537 Axona™ Accera age-associated memory Phase II Broomfield, CO impairment (303) 439-0004 AZD1446 AstraZeneca Alzheimer’s disease Phase II (TC-6683) Wilmington, DE (see also ADHD) (800) 236-9933 Targacept (336) 480-2100 Winston-Salem, NC bapineuzumab Janssen Alzheimer Alzheimer’s disease Phase III (AAB-001) Immunotherapy (intravenous) (800) 817-5286 South San Francisco, CA (Fast Track) (860) 732-5156 Pfizer ------New York, NY Alzheimer’s disease Phase II (subcutaneous) (800) 817-5286 (860) 732-5156 BAY 85-8101 Bayer HealthCare Alzheimer’s disease diagnosis Phase I (PET imaging agent) Pharmaceuticals (888) 842-2937 Wayne, NJ BAY 94-9172 Avid Radiopharmaceuticals Alzheimer’s disease diagnosis Phase III (florbetaben) Philadelphia, PA (215) 298-0700 (PET imaging agent) Bayer HealthCare (888) 842-2937 Pharmaceuticals Wayne, NJ begacestat Pfizer Alzheimer’s disease Phase I New York, NY (860) 732-5156 bisnorcymserine QR Pharma advanced Alzheimer’s disease Phase I (BNC) Radnor, PA (484) 253-2296 C105 Cognition Pharmaceuticals cognitive impairment/deficit Phase II New York, NY associated with multiple sclerosis (212) 906-7071 CAD106 CytosBiotechnology Alzheimer’s disease Phase II Postfach, Switzerland (888) 669-6682 Novartis Pharmaceuticals East Hanover, NJ

M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 9 D E M E N T I A S Product Name Sponsor Indication Development Status CEP-26401 Cephalon cognition disorders Phase I Frazer, PA (610) 344-0200 CERE-110 Ceregene Alzheimer’s disease Phase II (gene therapy) San Diego, CA (858) 458-8800 CHF 5074 Chiesi Pharmaceuticals Alzheimer’s disease Phase I Rockville, MD (301) 424-2661 CTS-21166 Astellas Pharma US Alzheimer’s disease Phase I Deerfield, IL (800) 695-4321 CoMentis (650) 359-2600 South San Francisco, CA davunetide Allon Therapeutics Alzheimer’s disease, Phase II intranasal Vancouver, Canada cognitive impairment (604) 736-0634 associated with schizophrenia davunetide Allon Therapeutics mild cognitive impairment Phase II intravenous Vancouver, Canada (604) 736-0634 DEBIO 9902 Debiopharm Alzheimer’s disease Phase I Lausanne, Switzerland www.debiopharm.com docosahexaenoic Martek Biosciences Alzheimer’s disease Phase III acid Columbia, MD (410) 740-0081 E2212 Eisai Alzheimer’s disease Phase I Woodcliff Lake, NJ (888) 274-2378 EGb 761 Ipsen Alzheimer’s disease Phase III Milford, MA (508) 478-8900 ELND005 Elan Pharmaceuticals Alzheimer’s disease Phase II South San Francisco, CA (Fast Track) (650) 877-0900 Transition Therapeutics (416) 260-7770 Toronto, Canada ELND006 Elan Pharmaceuticals Alzheimer’s disease Phase I South San Francisco, CA (650) 877-0900 EVP-0334 EnVivo Pharmaceuticals Alzheimer’s disease Phase I Watertown, MA (617) 225-4250 EVP-6124 EnVivo Pharmaceuticals Alzheimer’s disease Phase II Watertown, MA (see also schizophrenia) (617) 225-4250 Exebryl-1® ProteoTech Alzheimer’s disease Phase I Kirkland, WA (425) 823-0400 florbetapir F 18 Avid Radiopharmaceuticals Alzheimer’s disease diagnosis Phase III (PET imaging agent) Philadelphia, PA (215) 298-0700 Gammagard S/D™ Baxter Healthcare Alzheimer’s disease Phase III immune globulin Deerfield, IL (early-stage, mid-stage disease) (800) 422-9837 (IVIG) gamma secretase Bristol-Myers Squibb Alzheimer’s disease Phase II inhibitor Princeton, NJ (mild to moderate), (212) 546-4000 pre-dementia Alzheimer’s disease HPP-854 TransTech Pharma Alzheimer’s disease Phase I High Point, NC (336) 841-0300

10 M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 D E M E N T I A S Product Name Sponsor Indication Development Status HT-0712 Helicon Therapeutics cognition disorders Phase I Farmingdale, NY (631) 370-8818 HTC-867 Pfizer cognitive impairment associated Phase I New York, NY with schizophrenia (860) 732-5156 huperzine A Neuro-Hitech Alzheimer’s disease Phase II New York, NY (212) 594-1225 intravenous Grifols USA Alzheimer’s disease in clinical trials normal human Los Angeles, CA (888) 474-3657 immunoglobulin latrepirdine Medivation early-stage Alzheimer’s disease Phase III San Francisco, CA (415) 543-3470 Pfizer (860) 732-5156 New York, NY ------Alzheimer’s disease Phase I (combination therapy) (415) 543-3470 (860) 732-5156 Lipitor® Pfizer Alzheimer’s disease Phase III atorvastatin New York, NY (combination therapy) (860) 732-5156 Lu AE58054 Lundbeck cognitive impairment associated Phase II Deerfield, IL with schizophrenia (800) 455-1141 LY2886721 Eli Lilly Alzheimer’s disease Phase I Indianapolis, IN (800) 545-5979 MCD-386CR Mithridion Alzheimer’s disease Phase I Madison, WI (608) 443-2432 NIC5-15 Humanetics Alzheimer’s disease Phase II completed Eden Prairie, MN (952) 937-7660 NSA-789 Pfizer Alzheimer’s disease Phase I New York, NY (see also schizophrenia) (860) 732-5156 Oxigon™ Intellect Neurosciences Alzheimer’s disease Phase I indolepropionic New York, NY (212) 448-9300 acid derivative PF-3654746 Pfizer Alzheimer’s disease Phase I New York, NY (adjunctive treatment) (860) 732-5156 PF-3654764 Pfizer Alzheimer’s disease Phase I completed New York, NY (860) 732-5156 PF-4360365 Pfizer Alzheimer’s disease Phase II New York, NY (860) 732-5156 PF-4447943 Pfizer Alzheimer’s disease Phase II New York, NY (860) 732-5156 ------Alzheimer’s disease Phase I (combination therapy) (860) 732-5156 PF-4494700 Pfizer Alzheimer’s disease Phase II New York, NY (860) 732-5156 PF-5212365 Pfizer Alzheimer’s disease Phase II New York, NY (see also schizophrenia) (860) 732-5156

M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 11 D E M E N T I A S Product Name Sponsor Indication Development Status PF-5212377 Pfizer Alzheimer’s disease Phase II New York, NY (860) 732-5156 PF-5236806 Janssen Alzheimer Alzheimer’s disease Phase II Immunotherapy (800) 934-5556 South San Francisco, CA (212) 407-5740 Pfizer New York, NY Posiphen™ QR Pharma Alzheimer’s disease, Phase II R-phenserine Radnor, PA mild cognitive impairment (484) 253-2296 RG1450 Roche Alzheimer’s disease Phase I (gantenerumab) Nutley, NJ (973) 235-5000 RG1662 Roche Alzheimer’s disease Phase I Nutley, NJ (973) 235-5000 RG3487 Roche Alzheimer’s disease, cognitive Phase II Nutley, NJ impairment associated with (973) 235-5000 schizophrenia RG7412 Genentech Alzheimer’s disease Phase I (anti-Abeta) South San Francisco, CA (800) 626-3553 RVX-208 Resverlogix Alzheimer’s disease Phase I Calgary, Canada (403) 254-9252 SAR110894 sanofi-aventis Alzheimer’s disease Phase I Bridgewater, NJ (800) 633-1610 semagacestat Eli Lilly Alzheimer’s disease Phase III Indianapolis, IN (800) 545-5979 SEP-227900 Sepracor Alzheimer’s disease, Phase I Marlborough, MA cognition disorders (508) 481-6700 solanezumab Eli Lilly Alzheimer’s disease Phase III Indianapolis, IN (800) 545-5979 ST-101 Sonexa Therapeutics Alzheimer’s disease Phase II San Diego, CA (858) 356-6250 SYN-114 Synosia Therapeutics cognition disorders Phase I South San Francisco, CA (650) 244-4850 SYN-120 Synosia Therapeutics cognition disorders Phase I South San Francisco, CA (650) 244-4850 T-817MA Toyama Chemical Alzheimer’s disease Phase II Tokyo, Japan TC5619 AstraZeneca cognition disorders associated Phase II Wilmington, DE with schizophrenia (800) 236-9933 Targacept (see also ADHD) Winston-Salem, NC TD-5108 Theravance Alzheimer’s disease Phase I South San Francisco, CA (877) 275-8479 TD-8954 Theravance Alzheimer’s disease Phase I South San Francisco, CA (877) 275-8479

12 M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 D E M E N T I A S Product Name Sponsor Indication Development Status V950 Merck Alzheimer’s disease Phase I Whitehouse Station, NJ (800) 672-6372 varenicline Pfizer Alzheimer’s disease Phase II New York, NY (see also schizophrenia) (860) 732-5156

D E P R E S S I O N Product Name Sponsor Indication Development Status 163090 GlaxoSmithKline depression Phase I Rsch. Triangle Park, NC (see also anxiety disorders) (888) 825-5249 356278 GlaxoSmithKline depression Phase I Rsch. Triangle Park, NC (see also anxiety disorders) (888) 825-5249 424887 GlaxoSmithKline depression Phase I Rsch. Triangle Park, NC (see also anxiety disorders) (888) 825-5249 586529 GlaxoSmithKline depression Phase I Rsch. Triangle Park, NC (see also anxiety disorders) (888) 825-5249 Neurocrine Biosciences (858) 617-7600 San Diego, CA 588045 GlaxoSmithKline depression Phase I Rsch. Triangle Park, NC (see also anxiety disorders) (888) 825-5249 1014802 GlaxoSmithKline bipolar disorder Phase I Rsch. Triangle Park, NC (888) 825-5249 ABT-436 Abbott Laboratories depression Phase I Abbott Park, IL (see also anxiety disorders) (847) 937-6100 ADX N05 Shionogi Pharma depression Phase I Atlanta, GA (800) 461-3696 AZD2327 AstraZeneca depression Phase II Wilmington, DE (see also anxiety disorders) (800) 236-9933 AZD6765 AstraZeneca depression Phase II Wilmington, DE (800) 236-9933 AZD7268 AstraZenenca depression Phase II Wilmington, DE (800) 236-9933 BCI-540 BrainCells depression Phase II San Diego, CA (see also anxiety disorders) (858) 812-7700 BCI-952 BrainCells major depressive disorder Phase II San Diego, CA (858) 812-7700 bupropion IntelGenx depression application submitted (controlled-release) Quebec, Canada (514) 331-7440 cariprazine Forest Laboratories bipolar disorder Phase II New York, NY (see also schizophrenia) (800) 947-5227 ------depression Phase II (adjunctive treatment) (800) 947-5227

M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 13 D E P R E S S I O N Product Name Sponsor Indication Development Status Contrave™ Orexigen Therapeutics depression Phase II naltrexone/ La Jolla, CA (see also eating disorders) (858) 436-8600 bupropion combination Corlux™ Corcept Therapeutics psychotic major depression Phase III mifeprostone Menlo Park, CA (Fast Track) (650) 327-3270 CP-601927 Pfizer depression Phase II New York, NY (860) 732-5156 Cymbalta® Eli Lilly major depression in children and Phase III duloxetide Indianapolis, IN adolescents (800) 545-5979 depression therapy Eli Lilly depression Phase I Indianapolis, IN (800) 545-5979 DOV-21947 DOV Pharmaceutical depression Phase II Little Falls, NJ (see also eating disorders) (732) 907-3600 E2508 Eisai depression Phase I Woodcliff Lake, NJ (888) 274-2378 emicerfont GlaxoSmithKline depression Phase II Rsch. Triangle Park, NC (see also anxiety disorders) (888) 825-5249 Neurocrine Biosciences (858) 617-7600 San Diego, CA EVT-101 Evotec depression Phase II Hamburg, Germany Geodon® Pfizer bipolar disorders in adolescents Phase III ziprasidone New York, NY and children (860) 732-5156 GLYX-13 Naurex depression Phase I Evanston, IL www.naurex.com Invega® Johnson & Johnson bipolar disorder, manic episodes Phase III paliperidone Pharmaceutical Research (see also developmental disorders, (800) 817-5286 extended-release & Development schizophrenia, sleep disorders) Raritan, NJ Lamictal® GlaxoSmithKline bipolar disorder (elderly) Phase III completed lamotrigine Rsch. Triangle Park, NC (888) 825-5249 ------bipolar disorder (10-17 years) Phase III (888) 825-5249 levomilnacipran Forest Laboratories depression Phase III (F2695) New York, NY (800) 947-5227 losmapimod GlaxoSmithKline major depressive disorder Phase II Rsch. Triangle Park, NC (888) 825-5249 Lovaza® GlaxoSmithKline depression Phase II omega-3-acis Rsch. Triangle Park, NC (888) 825-5249 ethyl esters Lu AA21004 Lundbeck major depressive disorder Phase III Deerfield, IL (see also anxiety disorders) (800) 455-1141 Takeda Pharmaceuticals (224) 554-6500 North America Deerfield, IL

14 M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 D E P R E S S I O N Product Name Sponsor Indication Development Status Lu AA24530 Lundbeck major depressive disorder Phase I Deerfield, IL (see also anxiety disorders) (800) 455-1141 lurasidone Sepracor bipolar disorder Phase III Marlborough, MA (see also schizophrenia) (508) 481-6700 Motiva™ Neuren Pharmaceuticals post-stroke depression Phase II nefiracetam Bethesda, MD (301) 941-1830 Nectiv™ Pfizer treatment-resistant depression Phase II traxoprodil New York, NY (combination therapy) (860) 732-5156 nemifitide Tetragenex depression Phase II completed Pharmaceuticals (201) 505-1300 Park Ridge, NJ NERI Eli Lilly depressive disorders Phase II (LY2216684) Indianapolis, IN (see also ADHD) (800) 545-5979 NMDA receptor Evotec treatment-resistant depression Phase I antagonist Hamburg, Germany (973) 235-5000 Roche Nutley, NJ NSD-788 GlaxoSmithKline depression Phase I Rsch. Triangle Park, NC (see also anxiety disorders) (888) 825-5249 NeuroSearch Ballerup, Denmark Nuvigil® Cephalon bipolar depression Phase III armodafinil Frazer, PA (adjunctive treatment) (610) 344-0200 (see also eating disorders) OPC-34712 Otsuka America depression Phase II Pharmaceutical (adjunctive treatment) (800) 562-3974 Rockville, MD (see also ADHD, schizophrenia) orvepitant GlaxoSmithKline depression Phase II Rsch. Triangle Park, NC (see also anxiety disorders) (888) 825-5249 PF-4455242 Pfizer bipolar depression Phase I New York, NY (860) 732-5156 Pristiq® Pfizer major depressive disorder Phase II desvenlafaxine New York, NY in children and adolescents (860) 732-5156 RG1578 Roche depression Phase I Nutley, NJ (973) 235-5000 RG2417 Repligen bipolar disorder Phase II Waltham, MA (800) 622-2259 RG7090 Roche depression Phase II Nutley, NJ (see also developmental disorders) (973) 235-5000 RG7166 Roche depression Phase I Nutley, NJ (973) 235-5000 RG7351 Roche depression Phase I Nutley, NJ (973) 235-5000

M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 15 D E P R E S S I O N Product Name Sponsor Indication Development Status Risperdal® Johnson & Johnson bipolar disorder with anxiety or Phase III risperidone Pharmaceutical Research panic disorder (monotherapy), (800) 817-5286 & Development depression Raritan, NJ Serdaxin™ Rexahn Pharmaceuticals depressive disorders Phase II clavulanic acid Rockville, MD (240) 268-5300 Seroquel® AstraZeneca depression (monotherapy, application submitted quetiapine Wilmington, DE prevention of relapse) (800) 236-9933 fumarate (see also other) Seroquel XR® AstraZeneca bipolar depression in adolescents Phase III quetiapine Wilmington, DE and children (800) 236-9933 fumarate (see also addictive disorders, extended-release anxiety disorders, personality disorders) SPN 802 Supernus Pharmaceuticals bipolar disorder Phase I Rockville, MD (301) 838-2500 SSR125543 sanofi-aventis major depressive disorder Phase I Bridgewater, NJ (see also anxiety disorders) (800) 633-1610 SSR411298 sanofi-aventis depression Phase I Bridgewater, NJ (800) 633-1610 Staccato® Alexza Pharmaceuticals acute agitation in patients with application submitted loxapine Palo Alto, CA bipolar I disorder (650) 687-3900 inhalation (see also schizophrenia) SYN-111 Synosia Therapeutics bipolar disorder Phase II South San Francisco, CA (650) 244-4850 TC5214 AstraZeneca major depressive disorder Phase II Wilmington, DE (800) 236-9933 Targacept (336) 480-2100 Winston-Salem, NC TGBA01AD Fabre-Kramer depression Phase II Pharmaceuticals (713) 975-6900 Houston, TX triple reuptake Bristol-Myers Squibb depression in clinical trials inhibitor Princeton, NJ (212) 546-4000 TriRima® CeNeRx BioPharma depressive disorders Phase II (CX157) Rsch. Triangle Park, NC (see also anxiety disorders) (919) 234-4650 tasimelteon Vanda Pharmaceuticals depression Phase I Rockville, MD (see also sleep disorders) (240) 599-4500 vabicaserin Pfizer bipolar disorder Phase II New York, NY (see also schizophrenia) (860) 732-5156 Valdoxan® Novartis Pharmaceuticals major depressive disorder, Phase III agomelatine East Hanover, NJ prevention of depression relapse (888) 669-6682 venlafaxine Auspex Pharmaceuticals depression Phase I deuterium- Vista, CA (760) 599-1800 substituted (SD-254)

16 M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 D E P R E S S I O N Product Name Sponsor Indication Development Status verucerfont GlaxoSmithKline depression Phase II Rsch. Triangle Park, NC (see also anxiety disorders) (888) 825-5249 Neurocrine Biosciences (858) 617-7600 San Diego, CA vilazodone PGx Health major depression application submitted New Haven, CT (877) 274-9432 Vyvanse® Shire bipolar disorder Phase III lisdexamfetamine Wayne, PA (see also ADHD, schizophrenia, (434) 595-8800 dimesylate sleep disorders) ziprasidone Lipocine bipolar disorder Phase I extended-release Salt Lake City, UT (see also schizophrenia) (810) 994-7383

D E V E L O P M E N T A L D I S O R D E R S Product Name Sponsor Indication Development Status AFQ056 Novartis Pharmaceuticals fragile X syndrome Phase II completed East Hanover, NJ (see also addictive disorders) (888) 669-6682 CM-AT CureMark autism Phase III Rye, NY (Fast Track) (914) 925-3450 Invega® Johnson & Johnson aggression in adolescents and young Phase III paliperidone Pharmaceutical Research adults with autism (800) 817-5289 extended-release & Development (see also depression, schizophrenia, Raritan, NJ sleep disorders) RG7090 Roche fragile X syndrome Phase II Nutley, NJ (see also depression) (973) 235-5000 STK107 Seaside Therapeutics fragile X syndrome Phase I Cambridge, MA (617) 374-9009 STK209 Seaside Therapeutics autism in children and adolescents, Phase II (arbaclofen) Cambridge, MA fragile X syndrome (617) 374-9009

E A T I N G D I S O R D E R S Product Name Sponsor Indication Development Status 181771 GlaxoSmithKline bulimia nervosa Phase II completed Rsch. Triangle Park, NC (888) 825-5249 598809 GlaxoSmithKline compulsive over-eating Phase I Rsch. Triangle Park, NC (888) 825-5249 1521498 GlaxoSmithKline obesity Phase I Rsch. Triangle Park, NC (888) 825-5249 anamorelin Helsinn Therapeutics anorexia Phase II Bridgewater, NJ (Fast Track) (908) 231-1435 AZD4017 AstraZeneca obesity Phase I Wilmington, DE (800) 236-9933

M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 17 E A T I N G D I S O R D E R S Product Name Sponsor Indication Development Status AZD8329 AstraZeneca obesity Phase I Wilmington, DE (800) 236-9933 canagliflozin Johnson & Johnson obesity Phase II Pharmaceutical Research (800) 817-5286 & Development Raritan, NJ cetilistat Norgine obesity Phase II Amsterdam, www.norgine.com The Netherlands Contrave™ Orexigen Therapeutics obesity application submitted naltrexone/ La Jolla, CA (see also depression) (858) 436-8600 bupropion combination diazoxide choline Essentialis obesity Phase I (controlled-release) Carlsbad, CA (760) 431-2646 DOV-21947 DOV Pharmaceutical obesity Phase I Little Falls, NJ (see also depression) (732) 907-3600 Empatic™ Orexigen Therapeutics obesity Phase II zonisamide/ La Jolla, CA (858) 875-8600 bupropion GT389255 Peptimmune obesity Phase II Cambridge, MA (617) 715-8000 HHP-404 TransTech Pharma obesity Phase I High Point, NC (336) 841-0300 Histalean™ Obecure obesity Phase II betahistine Ramat Gan, Israel www.obecure.com JNJ-16269110 Johnson & Johnson obesity Phase II Pharmaceutical Research (800) 817-5286 & Development Raritan, NJ KD-3010 Kalypsys obesity Phase I San Diego, CA (858) 754-3300 lorcaserin Arena Pharmaceuticals obesity application submitted San Diego, CA (858) 453-7200 NN9161 Novo Nordisk obesity Phase I/II Princeton, NJ (609) 987-5800 Nuvigil® Cephalon binge eating disorder Phase III armodafinil Frazer, PA (see also depression) (610) 344-0200 OAP-189 Pfizer obesity Phase I New York, NY (860) 732-5156 obesity therapy Eli Lilly obesity Phase II Indianapolis, IN (800) 545-5979 pramlintide/ Amylin Pharmaceuticals obesity Phase II metreleptin San Diego, CA (858) 552-2200 combination Takeda Pharmaceuticals (877) 587-5332 North America Deerfield, IL

18 M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 E A T I N G D I S O R D E R S Product Name Sponsor Indication Development Status Qnexa™ VIVUS obesity application submitted phentermine/ Mountain View, CA (650) 934-5200 topiramate S-2367 Shionogi USA obesity Phase II Florham Park, NJ (973) 966-6900 S-234462 Shionogi USA obesity Phase I Florham Park, NJ (973) 966-6900 sobetirome QuatRx Pharmaceuticals obesity Phase I Ann Arbor, MI (734) 913-9900 TKS1225 Pfizer obesity Phase I New York, NY (860) 732-5156 TTP-435 TransTech Pharma obesity Phase I High Point, NC (336) 841-0300 Victoza® Novo Nordisk obesity Phase III liraglutide Princeton, NJ (second-line therapy) (609) 987-5800 ZGN-433 Zafgen obesity Phase I Cambridge, MA (617) 864-1645 Zoloft® Pfizer obesity in clinical trials sertraline New York, NY (see also anxiety disorders) (860) 732-5156 Zyprexa® Eli Lilly anorexia nervosa Phase II olanzapine Indianapolis, IN (see also personality disorders) (800) 545-5979

P E R S O N A L I T Y D I S O R D E R S Product Name Sponsor Indication Development Status Seroquel XR® AstraZeneca borderline personality disorder Phase III quetiapine Wilmington, DE (see also addictive disorders, (800) 236-9933 fumarate anxiety disorders, depression) extended-release Zyprexa® Eli Lilly borderline personality disorder Phase III completed olanzapine Indianapolis, IN (see also eating disorders) (800) 545-5979

P R E M E N S T R U A L D I S O R D E R S Product Name Sponsor Indication Development Status Lybrel™ Pfizer premenstrual dysphoric disorder Phase III levonorgestrel/EE New York, NY (860) 732-5156 PH80 Pherin Pharmaceuticals premenstrual dysphoric disorder, Phase II completed Redwood City, CA premenstrual syndrome (650) 568-1587

M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 19 S C H I Z O P H R E N I A Product Name Sponsor Indication Development Status 239512 GlaxoSmithKline schizophrenia Phase II Rsch. Triangle Park, NC (see also dementias) (888) 825-5249 729327 GlaxoSmithKline schizophrenia Phase I Rsch. Triangle Park, NC (888) 825-5249 773812 GlaxoSmithKline schizophrenia Phase II completed Rsch. Triangle Park, NC (888) 825-5249 1018921 GlaxoSmithKline schizophrenia Phase I Rsch. Triangle Park, NC (888) 825-5249 1034702 GlaxoSmithKline schizophrenia Phase I Rsch. Triangle Park, NC (see also dementias) (888) 825-5249 1144814 GlaxoSmithKline schizophrenia Phase I Rsch. Triangle Park, NC (888) 825-5249 Abilify® IM Depot Bristol-Myers Squibb schizophrenia Phase III aripiprazole Princeton, NJ (860) 732-5156 Otsuka America (800) 562-3974 Pharmaceutical Rockville, MD ABT-126 Abbott Laboratories schizophrenia Phase II Abbott Park, IL (see also dementias) (847) 937-6100 ABT-288 Abbott Laboratories schizophrenia Phase II Abbott Park, IL (see also dementias) (847) 937-6100 ADX71149 Johnson & Johnson schizophrenia Phase I Pharmaceutical Research (see also anxiety disorders) (800) 817-5286 & Development Raritan, NJ ATON005 Aton Pharma psychotic disorders Phase I Lawrenceville, NJ (609) 671-9010 AVN 211 Avineuro Pharmaceuticals schizophrenia Phase II San Diego, CA (858) 436-1537 AZD8418 AstraZeneca schizophrenia Phase I Wilmington, DE (800) 236-9933 AZD8529 AstraZeneca schizophrenia Phase II Wilmington, DE (800) 236-9933 BL-1020 BioLineRx schizophrenia Phase II Jerusalem, Israel www.biolinerx.com cariprazine Forest Laboratories schizophrenia Phase III New York, NY (see also depression) (800) 947-5227 CM-2395 Cenomed BioSciences schizophrenia in clinical trials Irvine, CA (949) 838-0344 DCCCyB Merck schizophrenia Phase I Whitehouse Station, NJ (800) 672-6372 EVP-6124 EnVivo Pharmaceuticals schizophrenia Phase II Watertown, MA (see also dementias) (617) 225-4250

20 M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 S C H I Z O P H R E N I A Product Name Sponsor Indication Development Status Fanapt™ Vanda Pharmaceuticals schizophrenia Phase I/II iloperidone Rockville, MD (240) 599-4500 (extended-release Novartis Pharmaceutical (888) 669-6682 injectable East Hanover, NJ formulation) idazoxan Potomac Pharma schizophrenia Phase II Bethesda, MD Invega® Johnson & Johnson schizophrenia in adolescents Phase III paliperidone Pharmaceutical Research (see also depression, developmental (800) 817-5286 extended-release & Development disorders, sleep disorders) Raritan, NJ ITI-007 Intra-Cellular Therapies schizophrenia Phase I New York, NY (see also sleep disorders) (212) 923-3344 JNJ-17305600 Johnson & Johnson schizophrenia Phase I Pharmaceutical Research (800) 817-5286 & Development Raritan, NJ JNJ-37822681 Johnson & Johnson schizophrenia Phase II Pharmaceutical Research (800) 817-5286 & Development Raritan, NJ JNJ-39393406 Johnson & Johnson schizophrenia Phase I Pharmaceutical Research (800) 817-5286 & Development Raritan, NJ JNJ-40411813 Johnson & Johnson psychotic disorders Phase I Pharmaceutical Research (800) 817-5286 & Development Raritan, NJ Lu 31-30 Lundbeck psychosis Phase II Deerfield, IL (800) 455-1141 lurasidone Sepracor schizophrenia application submitted Marlborough, MA (see also depression) (508) 481-6700 mGlu2/3 pro II Eli Lilly schizophrenia Phase II (LY2140023) Indianapolis, IN (800) 545-5979 MK-2637 Merck schizophrenia Phase I completed Whitehouse Station, NJ (800) 672-6372 MK-8998 Merck schizophrenia Phase II Whitehouse Station, NJ (800) 672-6372 NSA-789 Pfizer schizophrenia Phase I New York, NY (see also dementias) (860) 732-5156 OPC-34712 Otsuka America schizophrenia Phase II Pharmaceutical (see also ADHD, depression) (800) 562-3974 Rockville, MD PF-217830 Pfizer schizophrenia Phase II New York, NY (860) 732-5156

M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 21 S C H I Z O P H R E N I A Product Name Sponsor Indication Development Status PF-2400013 Pfizer schizophrenia Phase I New York, NY (860) 732-5156 PF-2545920 Pfizer schizophrenia Phase I New York, NY (860) 732-5156 PF-3463275 Pfizer schizophrenia Phase I New York, NY (860) 732-5156 PF-5212365 Pfizer schizophrenia Phase II New York, NY (see also dementias) (860) 732-5156 pimavanserin ACADIA Pharmaceuticals Parkinson’s disease-associated Phase III (ACP-103) San Diego, CA psychosis (858) 558-2871 Biovail ------Mississauga, Canada schizophrenia Phase II completed (858) 558-2871 RG1678 Roche schizophrenia Phase II completed Nutley, NJ (973) 235-5000 Risperdal® Consta® Johnson & Johnson schizophrenia Phase I risperidone Pharmaceutical Research (see also addictive disorders) (800) 817-5286 (injectable) & Development Raritan, NJ sabcomeline Proximagen Neuroscience schizophrenia Phase II London, United Kingdom Saphris® Merck psychotic disorders in elderly Phase III completed asenapine Whitehouse Station, NJ patients (800) 672-6372 SCH 900435 Merck schizophrenia Phase II Whitehouse Station, NJ (see also addictive disorders) (800) 672-6372 schizophrenia Eli Lilly schizophrenia Phase I therapy Indianapolis, IN (800) 545-5979 sertindole Lundbeck schizophrenia application submitted Deerfield, IL (800) 455-1141 Staccato® Alexza Pharmaceuticals acute agitation in schizophrenia application submitted loxapine Palo Alto, CA (see also depression) (650) 687-3900 inhalation TGOF02N Fabre-Kramer schizophrenia Phase II Pharmaceuticals (713) 975-6900 Houston, TX tiprolisant Bioprojet schizophrenia Phase II Paris, France www.bioprojet.com Ferrer Barcelona, Spain vabicaserin Pfizer schizophrenia Phase I New York, NY (see also depression) (860) 732-5156 varenicline Pfizer schizophrenia Phase II New York, NY (see also dementias) (860) 732-5156 Vyvanse® Shire schizophrenia Phase II lisdexamfetamine Wayne, PA (see also ADHD, depression, (434) 595-8800 dimesylate sleep disorders)

22 M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 S C H I Z O P H R E N I A Product Name Sponsor Indication Development Status ziprasidone Lipocine schizophrenia Phase I extended-release Salt Lake City, UT (see also depression) (810) 994-7383

S L E E P D I S O R D E R S Product Name Sponsor Indication Development Status 649868 GlaxoSmithKline sleep disorders Phase II Rsch. Triangle Park, NC (888) 825-5249 ABT-652 Abbott Laboratories excessive daytime sleepiness Phase I Abbott Park, IL (847) 937-6100 almorexant Actelion insomnia Phase III Pharmaceuticals US (650) 624-6900 South San Francisco, CA (888) 825-5249 GlaxoSmithKline ------Rsch. Triangle Park, NC insomnia in elderly Phase II (650) 624-6900 (888) 825-5249 AZ-007 Alexza Pharmaceuticals insomnia Phase I completed (zaleplon Mountain View, CA (650) 944-7000 inhalation) indiplon Neurocrine Biosciences insomnia application submitted (controlled-release) San Diego, CA (858) 617-7600 indiplon Neurocrine Biosciences insomnia application submitted (immediate-release) San Diego, CA (858) 617-7600 Intermezzo® Transcept Pharmaceuticals insomnia application submitted zolpidem Pt. Richmond, CA (510) 215-3500 sublingual Invega® Johnson & Johnson insomnia Phase II completed paliperidone Pharmaceutical Research (see also depression, developmental (800) 817-5286 extended-release & Development disorders, schizophrenia) Raritan, NJ ITI-007 Intra-Cellular Therapies sleep maintenance insomnia Phase II New York, NY (see also schizophrenia) (212) 923-3344 KRL-102 Krele Pharmaceuticals sleep disorders in clinical trials Saddle Brook, NJ (212) 923-3400 Lunesta® Sepracor ADHD-associated insomnia in Phase III eszopiclone Marlborough, MA adolescents and children (508) 481-6700 (see also anxiety disorders) LY2624803 Eli Lilly insomnia Phase II Indianapolis, IN (800) 545-5979 melatonin Neurim Pharmaceuticals non-24-hour sleep-wake disorder Phase III (controlled-release) Tel-Aviv, Israel www.neurim.com (Orphan Drug) MK-4305 Merck insomnia Phase III Whitehouse Station, NJ (800) 672-6372

M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 23 S L E E P D I S O R D E R S Product Name Sponsor Indication Development Status MK-6096 Merck insomnia Phase II Whitehouse Station, NJ (800) 672-6372 MN-305 MediciNova insomnia Phase II San Diego, CA (858) 373-1500 SKP-1041 Skye Pharma US sleep disorders Phase II (zaleplon Cambridge, MA (908) 901-0300 controlled-release) Somnus Therapeutics Bedminster, NJ tasimelteon Vanda Pharmaceuticals insomnia Phase III (Orphan Drug) Rockville, MD (see also depression) (240) 599-4500 ------circadian rhythm sleep disorder Phase II (240) 599-4500 TGAR01H Fabre-Kramer insomnia Phase II (triazolam Pharmaceuticals (713) 975-6900 intranasal) Houston, TX Vyvanse® Shire sleep disorders Phase I lisdexamfetamine Wayne, PA (ADHD, depression, schizophrenia) (434) 595-8800 dimesylate zaleplon-GR Intec Pharma insomnia Phase I Jerusalem, Israel www.intecpharma.com

O T H E R Product Name Sponsor Indication Development Status CORT 108297 Corcept Therapeutics psychiatric disorders Phase I Menlo Park, CA (650) 327-3270 MK-8368 Merck psychiatric disorders Phase I Whitehouse Station, NJ (800) 672-6372 Seroquel® AstraZeneca delirium Phase III quetiapine Wilmington, DE (see also depression) (800) 236-9933 fumarate

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 July 5, 2010. 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 www.phrma.org | www.innovation.org | www.pparx.org | www.buysafedrugs.info | www.sharingmiracles.com Provided as a Public Service by PhRMA. Founded in 1958 as the Pharmaceutical Manufacturers Association. Copyright © 2010 by the Pharmaceutical Research and Manufacturers of America. Permission to reprint is awarded if proper credit is given.

24 M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 G L O S S A R Y

Alzheimer’s disease—Progressive attention deficit/hyperactivity loss of ability to experience plea- and chronic deterioration of all disorder—ADHD is a complex sure and interest, fatigue, feelings mental functions. Early manifesta- neurological impairment that of worthlessness or guilt, difficulty tions include a decrease in attention results in an overactive behavior in concentrating, and preoccupa- span, impaired powers of concen- pattern and a difficulty concen- tion with death or a wish to die. tration, some personality change trating. While it primarily affects Major depression is associated with and forgetfulness. As the disease children, a growing number of impairment in social functioning. progresses, there is a loss of com- adults are being diagnosed with If criteria for major depression putational ability, in addition to the disorder. Boys are afflicted have been met but in addition an word-finding problems and difficulty some three times as often as girls. episode of mania has ever occurred, with ordinary activities. Ultimately, Children with ADHD are full of then the diagnosis becomes bipolar there is severe memory loss, complete energy, fidgety, impulsive, reck- disorder (or manic-depressive disorientation, social withdrawal less, irritable, emotionally illness). The essential feature of loss of independence, and is fatal. immature and aggressive. Because mania is a distinct period when It is the seventh leading cause of their attention span is short, they the predominant mood is either death in the United States. do not conform to orderly routine. elevated, expansive, or irritable, ADHD often leads to anti-social with associated symptoms including anxiety disorders—A group of acts and difficulty learning, hyper activity, pressure of speech, mental illnesses in which symp- although IQ is normal. No definite flight of ideas, inflated self-esteem, toms of anxiety (from mild unease cause has been established, but decreased need for sleep, dis- to intense fear) are the main feature some researchers now believe tractibility and excessive and there is overlap among specific heredity plays a role. involvement in activities that often syndromes. Generalized anxiety are flamboyant, bizarre or disor- disorder is diagnosed if a patient autism—A complex developmental ganized. experiences unrealistic or excessive disorder that causes severe and anxiety and worry (apprehensive pervasive impairment in thinking, Fast Track—Fast Track is a process expectation) about two or more feeling, language, and the ability to designed to facilitate the develop- life circumstances, e.g., worry relate to others. It is usually first ment and expedite the review of about something bad happening diagnosed in early childhood and drugs to treat serious diseases and to a loved one (who is not in ranges from a severe form, called fill an unmet medical need. The danger) and worry about money autism disorder, through pervasive status is assigned by the U.S. Food (for no reason) for six months or development disorder, to a much and Drug Administration. The longer. A diagnosis of panic dis- milder form, Asperger syndrome. purpose is to get important new order requires that panic attacks drugs to the patient earlier. Fast —sudden feelings of apprehension dementia—Degeneration of Track addresses a broad range of or fear accompanied by physical central nervous system functions, serious diseases. Generally, deter- symptoms such as shortness of such as memory and learning mining factors include whether the breath—occur with 4 out of 12 capacity. The natural decline of drug will have an impact on such concomitant psychophysiological these functions with age is grossly factors as survival, day-to-day func- symptoms, that the attacks are exaggerated in dementia. tioning, or the likelihood that the severe enough and happen often depression—A feeling of intense disease, if left untreated, will enough to be disruptive or dis- sadness, which may follow a progress from a less severe condi- tressing to the individual, and recent loss or other sad event but tion to a more serious one. Filling that at least one attack was spon- is out of proportion to that event an unmet medical need is defined taneous, i.e., occurred in the and persists beyond an appropriate as providing a therapy where none absence of a phobic stimulus. length of time. Major depressive exists or providing a therapy which may be potentially superior to application submitted—An appli- disorder (or major depression syndrome) includes an episode of existing therapy. Once a drug cation for marketing has been receives Fast Track designation, submitted to the U.S. Food and depression defined as a persistent (for at least 2 weeks) mood distur- early and frequent communication Drug Adminis tration (FDA). The between the FDA and a drug application can either be an NDA bance, plus at least 4 of the following: sleep disturbance, company is encouraged throughout (new drug application) or a BLA the entire drug development and (biologic license application). changes in psychomotor activity,

M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 25 G L O S S A R Y

review process. The frequency of tive behavior that is usually irra- premenstrual syndrome communication assures that ques- tional and bizarre. (PMS)/pre menstrual dysphoric tions and issues are resolved disorder (PMDD) —PMS refers to quickly, often leading to earlier Orphan Drug—A drug to treat a the variation of physical and mood drug approval and access by disease that has a patient popula- symptoms that appear during the patients. tion of 200,000 or less, or a disease last one or two weeks of the men- that has a patient population of strual cycle and disappear by fragile X syndrome (FXS)—The more than 200,000 and a develop- the end of a full flow of menses. most common cause of inherited ment cost that will not be recovered Psychiatrists and other mental health mental impairment. This impair- from sales in the United States. workers tend to use the term PMDD ment can range from learning Orphan Drug status is assigned by to describe a specific set of mood disabilities to more severe cognitive the U.S. Food and Drug symptoms that interfere with social or intellectual disabilities. FXS is Administration. or role functioning that are also the most common known cause of present the week before menses autism or “autistic-like” behaviors, Phase 0—First-in-human trials conducted in accordance with and remit a few days after the start. but 80-85 percent of autism cases PMS looks more at physical symp- are of unknown cause. Symptoms FDA’s 2006 guidance on exploratory Investigational New toms such as bloating, breast also can include characteristic tenderness and appetite change. physical and behavioral features Drug (IND) studies designed to speed up development of promis- PMDD has as part of its definition and delays in speech and language symptoms such as depressed mood, development. ing drugs by establishing very early on whether the agent anxiety or tension, irritability, obesity—For adults, overweight behaves in human subjects as concentration difficulties, overeat- and obesity ranges are determined was anticipated from preclinical ing or food cravings, and feeling by using weight and height to cal- studies. overwhelmed. culate the “body mass index” Phase I—Safety testing and psychosis—Severe mental disor- (BMI). BMI is used because, for ders in which the individual loses most people, it correlates with their pharma cological profiling of new drugs in small numbers of humans. contact with reality. Symptoms amount of body fat. Adults with a include delusions, hallucinations, BMI between 25 and 29.9 are con- Phase II—Effectiveness testing and thought disorders, loss of emotion, sidered overweight. An adult BMI identification of side effect profile mania and depression. of 30 or higher is considered of new drugs in humans. obese. schizophrenia—The most common Phase III—Extensive clinical trials form of psychotic illness charac- obsessive-compulsive disorder— in humans to verify effectiveness terized by disturbances in thinking, A neurosis characterized primarily and monitor adverse reactions of emotional reaction and behavior. by recurrent and persistent thoughts new drugs. It is disabling and has a prolonged that are intense, disgusting, fright- Phase IV—Additional post-market- course that almost always results ening, absurd or otherwise alien, in chronic ill health and some accompanied by ritualized, repeti- ing testing of drugs sometimes required by FDA. degree of personality change.

26 M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 S E L E C T E D F A C T S A B O U T M E N T A L I L L N E S S E S A N D A D D I C T I V E D I S O R D E R S Overview • Hundreds of millions of people worldwide are affected by mental, behavioral, neurological, and substance use disorders. In 2002, the World Health Organization (WHO) estimated that globally 154 million people suffered from depression and 25 million from schizophrenia. Another 91 million people were affected by alcohol use disorders and 15 million by drug use disorders. WHO also estimates that 24 million people suffer from Alzheimer’s disease and other dementias.1 • An estimated 26.2 percent of Americans ages 18 and older—about one in four adults—suffer from a diagnosable mental disorder in a given year. When applied to the 2004 U.S. Census residential population estimate for ages 18 and older, that figure translates to 57.7 million people. Mental disorders are the leading cause of disability in the United States and Canada for ages 15-44. Many people suffer from more than one mental disorder at a given time. Nearly half (45 percent) of those with any mental disorder meet the criteria for two or more disorders.2 • Mental illness, including suicide, accounts for more than 15 percent of the burden of disease in established market economies, which is more than the disease burden caused by all cancers.2 Worldwide, about 877,000 people die by suicide every year.1 • In 2006, suicide was the eleventh leading cause of death in the United States, accounting for 33,300 deaths. The overall rate was 10.9 suicide deaths per 100,000 people. An estimated 12 to 25 attempted suicides occur per every suicide death. Suicide was the seventh leading cause of death for males and the sixteenth leading cause of death for females in 2006. Almost four times as many males as females die by suicide.2 • Serious mental illnesses cost the United States more than $317 billion in lost wages, health care expenditures and disability benefits each year.2 Addictive Disorders • Substance abuse affects an estimated 25 million Americans, and another 40 million people, such as families of abusers and those injured or killed by intoxicated drivers, are affected indirectly. Alcoholism afflicts 10 million adults and 3 million children. An estimated 12.5 million Americans are addicted to other drugs, such as barbitu- rates, opiates, sedatives, and hallucinogens.3 • The estimated economic cost of alcohol abuse in 1998 was $184.6 billion, or $638 for every man, woman, and child in the United States. Alcohol-related injuries alone cost an estimated $47 billion annually.4 • The Office of National Drug Control Policy reported that in 2002, the economic cost of drug abuse to the United States was $180.9 billion.5 Alzheimer’s Disease/Dementias6 • Today, 5.3 million people are living with Alzheimer’s—every 70 seconds, someone develops the disease. Some 5.1 million people with Alzheimer’s are age 65 and older, but an estimated 500,000 people younger than age 65 either have Alzheimer’s or another dementia. • Alzheimer’s disease is the most common type of dementia, accounting for 60 percent to 80 percent of cases. Vascular dementia (also called multi-infarct dementia, post-stroke dementia, or vascular cognitive impairment) is considered the second most common type after Alzheimer’s. • In 2000, an estimated 411,000 new cases of Alzheimer’s were diagnosed. That number was expected to increase to 454,000 new cases a year by 2010; 615,000 annually by 2030; and 959,000 new cases a year by 2050. By that year, the number of people age 65 and older with Alzheimer’s could be as high as 16 million unless researchers find a way to prevent or treat the disease. • In 2006, Alzheimer’s was listed as the “underlying cause of death” for 72,432 Americans. In 1991, only 14,112 death certificates recorded Alzheimer’s as the underlying cause. From 2000-2006, deaths from Alzheimer’s increased by 46.1 percent, while the number one cause of death, heart disease, decreased by 11.1 percent. In 2006, Alzheimer’s was the seventh leading cause of death for people of all ages and the fifth in people age 65 and older.

M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 27 S E L E C T E D F A C T S A B O U T M E N T A L I L L N E S S E S A N D A D D I C T I V E D I S O R D E R S Alzheimer’s Disease/Dementias 6 (continued) • Some 70 percent of people with Alzheimer’s and other dementias live at home, where they are cared for by family and friends. In 2009, nearly 11 million family members and friends provided an average of 21.9 hours of unpaid care per week for a person with Alzheimer’s disease or another dementia, for a total of about 12.5 billion hours of care. That year, the estimated economic value of the unpaid care was $144 billion. About 60 percent of family and other unpaid caregivers of people with Alzheimer’s disease and other dementias are women. • People with Alzheimer’s disease and other dementias are high users of health care, long-term care and hospice. Total payments for these types of care from all sources, including Medicare and Medicaid, are three times higher for older people with Alzheimer’s and other dementias than for other older people. Based on the average per person payments from all sources for health care and long-term care services for people aged 65 and older with Alzheimer’s disease and other dementias in 2004, total payments for 2010 are expected to be $172 billion, including $123 billion for Medicare and Medicaid. Anxiety Disorders 2 • Anxiety disorders, which include panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, generalized anxiety disorder, and phobias, affect some 40 million adults ages 18 and older, or about 18.1 percent of people in this age group in a given year. • About 6.8 million American adults ages 18 and older, or about 3.1 percent of people in this age group, have generalized anxiety disorder (GAD) each year. The median age of onset is 31. • Some 2.2 million U.S. adults age 18 and older, or about 1 percent of people in that age group, have obsessive- compulsive disorder (OCD) in a given year. The median age of onset is 19. • Approximately 6 million Americans ages 18 and older have panic disorder, or about 2.7 percent of people in that age group. • About 7.7 million U.S. adults age 18 and older, or about 3.5 percent of that age group, have post-traumatic stress disorder (PTSD), in a given year. PTSD can develop at any age, but the median age of onset is 23. • About 15 million American adults ages 18 and older, or about 6.8 percent of people in this age group, have social phobia yearly. The disorder typically begins around age 13. Attention-Deficit/Hyperactivity Disorder (ADHD) • Attention-deficit/hyperactivity disorder (ADHD) is one of the most common reasons children are referred for mental health services. It affects as many as one in every 20 children, and boys are three to four times more likely than girls to experience the disorder.3 • ADHD usually becomes evident in preschool or early elementary years. The median age of onset is seven years, although the disorder can persist into adolescence and occasionally into adulthood.2 Although most children with ADHD have normal or above-normal intelligence, 40 percent to 60 percent have serious learning difficulties.3 Autism 2 • (Estimating the prevalence of autism is difficult and controversial due to differences in the ways that cases are identified and defined, differences in study methods, and changes in diagnostic criteria.) A recent study reported the prevalence of autism among 8-year-olds to be about 1 in 110. Autism and other autism spectrum disorders (ASDs) develop in childhood and generally are diagnosed by age three. • Autism is about four times more common in boys than girls; however, girls with the disorder tend to have more severe symptoms and greater cognitive impairment. Depression • Mood disorders, which include major depressive disorder, dysthymic disorder, and bipolar disorder, affect nearly 21 million U.S. adults, or about 9.5 percent of the U.S. population age 18 and older in a given year. The median age of onset for mood disorders is age 30. These disorders often co-occur with anxiety disorders and substance abuse.2

28 M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 S E L E C T E D F A C T S A B O U T M E N T A L I L L N E S S E S A N D A D D I C T I V E D I S O R D E R S Depression (continued) • Bipolar disorder affects about 5.7 million American adults, or about 2.6 percent of the U.S. population age 18 and older yearly. The median age of onset for this disorder is age 25.2 • Dysthymic disorder (chronic, mild depression) affects some 1.5 percent of the U.S. population age 18 and older (about 3.3 million people) in a given year. The median age of onset is 31.2 • Major depressive disorder is the leading cause of disability in the United States for ages 15-44, affecting nearly 15 million American adults (about 6.7 percent of the U.S. population age 18 and older) in a given year. The dis- order can develop at any age, but the median age at onset is 32. Major depressive disorder is more prevalent in women than in men.2 • Clinical depression has become one of America’s most costly illnesses. Left untreated, depression is as costly as heart disease or AIDS to the U.S. economy, costing more than $43.7 billion in absenteeism from work (more than 200 million days lost from work each year), lost productivity and direct treatment costs. Depression tends to affect people in their prime working years and may last a lifetime if untreated. More than 80 percent of people with clinical depression can be successfully treated.3 Eating Disorders • In their lifetime, an estimated 0.6 percent of the adult population in the United States will suffer from anorexia, 1.0 percent from bulimia, and 2.8 percent from a binge-eating disorder. Women are much more likely than males to develop an eating disorder. They are three times as likely to experience anorexia (0.9 percent of women vs. 0.3 percent of men) and bulimia (1.5 percent of women vs. 0.5 percent of men). They are also 75 percent more likely to have a binge-eating disorder (3.5 percent of women vs. 2.0 percent of men).2 • The mortality rate among people with anorexia has been estimated at 0.56 percent per year, or approximately 5.6 percent per decade, which is about 12 times higher than the annual death rate due to all causes of death among females ages 15-24 in the general population.2 • An estimated 32.7 percent of U.S. adults 20 years and older are overweight, 34.3 percent are obese, and 5.9 percent are extremely obese. Compared with whites, African Americans have a 51 percent higher prevalence rate of obesity and Hispanics have a 21 percent higher rate.7 • In 2004, the U.S. Centers for Disease Control and Prevention (CDC) ranked obesity as the number one health risk facing America. Obesity causes an estimated 400,000 deaths a year and costs the national economy nearly $122.9 billion annually.8 Premenstrual Disorders • Premenstrual syndrome (PMS) is estimated to affect up to 75 percent of women during their childbearing years. It occurs more often in women between their late 20s and early 40s, those with at least one child, those with a family history of a major depressive disorder, or women with a past medical history of either postpartum depres- sion or an affective mood disorder. Up to 60 percent of women with severe PMS have an underlying psychiatric disorder.9 • Premenstrual dysphoric disorder (PMDD), a very severe form of PMS, affects about 5 percent of menstruating women.10 Schizophrenia • Schizophrenia strikes some 2.4 million American adults, or about 1.1 percent of the U.S. population age 18 and older, in a given year, affecting men and women with equal frequency. The disorder first appears in men in their late teens or early 20s, while women are generally affected in their 20s or early 30s.2 • The appearance of schizophrenic symptoms before age 12 is rare—less than one-sixtieth as common as the adult-onset type. Neurodevelopmental damage seems to be greater in childhood schizophrenia than in the adult- onset type. Most schizophrenic children show delays in language and other functions long before their psychotic symptoms (hallucinations, delusions, and disordered thinking) appear, usually at age seven or later. In the first years of life, about 30% of these children have transient symptoms of pervasive developmental disorder, such as rocking, posturing, and arm flapping.3

M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 29 S E L E C T E D F A C T S A B O U T M E N T A L I L L N E S S E S A N D A D D I C T I V E D I S O R D E R S Schizophrenia (continued) • Schizoaffective disorder, a combination of symptoms of schizophrenia and a mood disorder, may range from two to five in 1,000 people (i.e., 0.2 percent to 0.5 percent) and may account for one-fourth or even one-third of all people with schizophrenia.11 Sources: 1. World Health Organization, www.who.int 2. National Institute of Mental Health, www.nimh.nih.gov 3. Mental Health America, www.mentalhealthamerica.net, www.nmha.org 4. Community Safety Series, www.be-safe.org 5. U.S. Department of Justice, www.usdoj.gov 6. Alzheimer’s Association, www.alz.org 7. Centers for Disease Control and Prevention, www.cdc.gov 8. ObesityinAmerica.org, (The Endocrine Society and The Hormone Foundation), www.obesityinamerica.org 9. National Library of Medicine, www.nlm.nih.gov 10. Madison Institute of Medicine, Inc., www.pmdd.factsforhealth.org 11. National Alliance on Mental Illness, www.nami.org

30 M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 T H E D R U G D I S C O V E R Y , D E V E L O P M E N T A N D A P P R O V A L P R O C E S S It takes 10-15 years on average for an experimental drug to travel from the lab to U.S. patients. Only five in 5,000 compounds that enter preclinical testing make it to human testing. One of these five tested in people is approved.

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T H E D R U G D E V E L O P M E N T A N D A P P R O V A L P R O C E S S

he U.S. system of new drug approvals is perhaps study a drug’s safety profile, including the safe dosage Tthe most rigorous in the world. range. The studies also determine how a drug is It takes 10-15 years, on average, for an experimental absorbed, distributed, metabolized, and excreted as drug to travel from lab to U.S. patients, according to well as the duration of its action. the Tufts Center for the Study of Drug Development, Clinical Trials, Phase II. In this phase, controlled based on drugs approved from 1994 through 1998. trials of approximately 100 to 500 volunteer patients Only five in 5,000 compounds that enter preclinical (people with the disease) assess a drug’s effectiveness testing make it to human testing. And only one of those and determine the early side effect profile. five is approved for sale. Clinical Trials, Phase III. This phase usually involves On average, it costs a company $1.3 billion to get 1,000 to 5,000 patients in clinics and hospitals. one new medicine from the laboratory to U.S. patients, Physicians monitor patients closely to confirm efficacy according to a 2007 study by the Tufts Center for the and identify adverse events. Study of Drug Development. New Drug Application (NDA)/Biologic License Once a new compound has been identified in the Application (BLA). Following the completion of all laboratory, medicines are developed as follows: three phases of clinical trials, a company analyzes all Preclinical Testing. A pharmaceutical company con- of the data and files an NDA or BLA with FDA if the ducts laboratory and animal studies to show biological data successfully demonstrate both safety and effec- activity of the compound against the targeted disease, tiveness. The applications contain all of the scientific and the compound is evaluated for safety. information that the company has gathered. Applications typically run 100,000 pages or more. Investigational New Drug Application (IND). After The average review time for the 25 new therapeutics completing preclinical testing, a company files an IND approved by the FDA in 2009 was 13.3 months. with the U.S. Food and Drug Administration (FDA) to begin to test the drug in people. The IND shows results Approval. Once FDA approves an NDA or BLA, the of previous experiments; how, where and by whom new medicine becomes available for physicians to the new studies will be conducted; the chemical prescribe. A company must continue to submit periodic structure of the compound; how it is thought to work reports to FDA, including any cases of adverse reactions in the body; any toxic effects found in the animal and appropriate quality-control records. For some studies; and how the compound is manufactured. All medicines, FDA requires additional trials (Phase IV) to clinical trials must be reviewed and approved by the evaluate long-term effects. Institutional Review Board (IRB) where the trials will Discovering and developing safe and effective new be conducted. Progress reports on clinical trials must medicines is a long, difficult, and expensive process. be submitted at least annually to FDA and the IRB. Pharmaceutical companies invested an estimated Clinical Trials, Phase I. These tests usually involve $65.3 billion in research and development in 2009. about 20 to 100 normal, healthy volunteers. The tests

M E D I C I N E S I N D E V E L O P M E N T F O R Mental Illnesses 2010 31 T R A C K I N G T H E P H A R M A C E U T I C A L A N D B I O T E C H N O L O G Y R E S E A R C H P I P E L I N E S

Today, more than 2,900 new medicines are in devel- disease, pharmaceutical and biotechnology opment in the United States. Many of these potential researchers are working on new medicines to treat new medicines will fail in clinical trials, but some it and related conditions. The 2010 report found may represent tomorrow’s new treatments. Bringing 235 medicines in the pipeline. each new medicine to patients will require, on • Mental Illnesses—Pharmaceutical and biotech- average, 10 to 15 years of testing and review. nology researchers are testing many new medi- PhRMA publishes several reports that track the cines to help the more than 450 million people pharmaceutical and biotechnology research pipelines worldwide who suffer from some form of mental for many diseases, including the leading causes of illness. The 2010 report found 313 medicines in death among Americans—heart disease, cancer, and the pipeline. stroke. The reports include medicines currently in • Biotechnology—Millions of people have already clinical trials or at the U.S. Food and Drug benefited from medicines and vaccines developed Administration (FDA) for review. Below is a summary through biotechnology, and a new report offers of our most popular reports. hope that many more will benefit in the future. The • Cancer—There are few things that cause patients 2008 report found 633 medicines in the pipeline. more fear and uncertainty as a cancer diagnosis. • Children—Biopharmaceutical researchers are Yet today—because of a steady stream of new and testing medicines to meet the special needs of chil- improved medicines and treatments—cancer can dren. These medicines offer hope that the increasingly be managed and even beaten. The significant improvements achieved in children’s 2009 report found 861 medicines in the pipeline. health over the past few decades will continue and • Heart Disease and Stroke—Keeping up the even accelerate. The 2010 report found 234 medi- momentum of drug discovery that has helped cut cines in clinical trials. deaths from heart disease and stroke in half in the • Older Americans—The population of Americans past three decades, biopharmaceutical companies over 65 is surging, and the pace will only increase are working on new medicines for these diseases. over the coming years. As life expectancy contin- The 2009 report found 312 medicines in the ues to expand, older Americans face new and pipeline. growing challenges to their health, productivity and • Diabetes—Approximately 4,110 people are diag- independence. The 2008 report found 1,026 medi- nosed with diabetes every day. To help fight this cines in the pipeline.

New Medicines. New Hope.®

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