在研抗阿尔兹海默病药物（2012年）

Today, more than 5 million Americans are suf- fering from Alzheimer’s disease. The disease ravages the minds of patients, crushes entire families and currently costs the health care system $200 billion a year. These sobering statistics are projected to get much worse as the 76 million American baby boomers age. If no new medicines are found to prevent, delay or stop the progression of Alzheimer’s disease, the number of people affected in America will jump to 13.5 million by 2050, according to the Alzheimer’s Association. Costs for care for Alzheimer’s patients will increase five-fold to $1.08 trillion a year. Even modest progress can drastically change this trajectory. A breakthrough medicine that delays the onset of Alzheimer’s disease by just five years could decrease the number of Americans suffering from the disease in 2050 by 43 percent and the related costs of care by $447 billion. Hope for the future lies in medical innovation. America’s biopharmaceutical companies cur- rently have 93 medicines in development for Alzheimer’s disease and dementias—either in human clinical trials or awaiting U.S. Food and Drug Administration (FDA) review. They are exploring various new approaches to treating Alzheimer’s disease, including: • A medicine that inhibits the formation and accumulation of amyloid-beta and tau protein deposits. • An intranasal medicine that is able to penetrate the blood-brain barrier for mild cognitive impairment, a precursor to Alzheimer’s. • A gene therapy for the treatment of Alzheimer’s disease. The quest is intense and financially risky. It takes, on average, more than $1 billion and 10 to 15 years to develop a new medicine. But new scientific advances are increasing our knowledge, and researchers are using every cutting-edge tool at their disposal. With contin- ued dedication, we hope to make a difference for every person at risk of suffering from this terrible, debilitating disease. Biopharmaceutical Research Companies are Developing Nearly 100 Medicines for Alzheimer’s Disease and Other Dementias Medicines in Development Alzheimer’s DiseAse presented by america’s biopharmaceutical research companies 2012 RepoRt 81 11 5 Co gn itio n Di so rd er s Di ag no sti cs Al zh eim er ’s D ise as e De m en tia s 2 Medicines in Development For Alzheimer’s Disease* * Some medicines are in development for more than one disorder. Medicines in Development Alzheimer’s Disease 20122 *For more information about a specific medicine in this report, please call the telephone number listed. Medicines in Development for Alzheimer’s Disease Alzheimer’s DiseAse AnD DementiAs product Name Sponsor Indication Development Status* AAB-002 (amyloid beta-protein inhibitor mAb) Janssen Alzheimer Immunotherapy South San Francisco, CA Pfizer New York, NY Alzheimer’s disease Phase 0 (888) 381-4595 (800) 879-3477 AAB-003/PF-05236812 (amyloid beta-protein inhibitor mAb) Janssen Alzheimer Immunotherapy South San Francisco, CA Pfizer New York, NY Alzheimer’s disease Phase I (888) 381-4595 (800) 879-3477 ABT-126 (alpha-7 neuronal nicotinic receptor antagonist) Abbott Laboratories Abbott Park, IL mild to moderate Alzheimer’s disease -------------------------------------------------- Alzheimer’s disease (combination therapy), Alzheimer’s disease (elderly) Phase II (847) 937-6100 ------------------------------------------- Phase I (847) 937-6100 ABT-288 (neurotransmitter receptor modulator) Abbott Laboratories Abbott Park, IL Alzheimer’s disease Phase II (847) 937-6100 ABT-384 Abbott Laboratories Abbott Park, IL mild to moderate Alzheimer’s disease Phase II (847) 937-6100 ABT-560 (alpha-4 beta-2 nicotinic receptor modulators) Abbott Laboratories Abbott Park, IL cognitive disorders Phase I (847) 937-6100 ABT-957 (calpain inhibitor) Abbott Laboratories Abbott Park, IL Alzheimer’s disease Phase I (847) 937-6100 ACC-002 (amyloid-beta peptide conjugate) Janssen Alzheimer Immunotherapy South San Francisco, CA Pfizer New York, NY Alzheimer’s disease Phase 0 (888) 381-4595 (800) 879-3477 AD02 vaccine Affiris Vienna, Austria GlaxoSmithKline Rsch. Triangle Park, NC Alzheimer’s disease Phase II (888) 825-5249 AD03 vaccine Affiris Vienna, Austria GlaxoSmithKline Rsch. Triangle Park, NC Alzheimer’s disease Phase I (888) 825-5249 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 ADS-8704 (donepezil/memantine) Adamas Pharmaceuticals Emeryville, CA moderate to severe Alzheimer’s disease Phase II (510) 450-3500 APH-0703 Aphios Woburn, MA Alzheimer’s disease, cognitive disorders Phase I/II (781) 932-6933 ARC029 (soluble amyloid reducing/clearing agent) (orphan Drug) Archer Pharmaceuticals Sarasota, FL mild to moderate Alzheimer’s disease Phase I (941) 755-6644 ARC031 (soluble amyloid reducing/clearing agent) Archer Pharmaceuticals Sarasota, FL Alzheimer’s disease Phase I (941) 755-6644 ASP0777 Astellas Pharma US Deerfield, IL dementia associated with Alzheimer’s disease Phase I (800) 695-4321 AVN 101 (serotonin 6 receptor antagonist) Avineuro Pharmaceuticals San Diego, CA cognitive enhancer in Alzheimer’s disease Phase II (858) 436-1537 AVN 322 (serotonin 6 receptor antagonist) Avineuro Pharmaceuticals San Diego, CA Alzheimer’s disease Phase I (858) 436-1537 AVN 397 Avineuro Pharmaceuticals San Diego, CA Alzheimer’s disease Phase II (858) 436-1537 AZD1446 (alpha4/beta2 neuronal nicotinic receptor agonist) AstraZeneca Wilmington, DE Targacept Winston-Salem, NC Alzheimer’s disease Phase I (800) 236-9933 (336) 480-2100 AZD3480 (ispronicline) AstraZeneca Wilmington, DE Targacept Winston-Salem, NC Alzheimer’s disease Phase II (800) 236-9933 AZD4694 (fluorine-18 labeled precision radiopharmaceutical) Navidea Biopharmaceuticals Dublin, OH Alzheimer’s disease (diagnosis) Phase II (614) 793-7500 AZD5213 (histamine-3 receptor antagonist) AstraZeneca Wilmington, DE Alzheimer’s disease Phase II (800) 236-9933 Medicines in Development Alzheimer’s Disease 20124 Medicines in Development for Alzheimer’s Disease ALZHEIMER’S DISEASE AND DEMENTIAS Product Name Sponsor Indication Development Status ß secretase inhibitor Eli Lilly Indianapolis, IN Alzheimer’s disease Phase II (800) 545-5979 BAN2401 (amyloid beta-protein inhibitor) BioArtic Neuroscience Stockholm, Sweden Eisai Woodcliff Lake, NJ mild to moderate Alzheimer’s disease Phase I www.bioarti.se (888) 274-2378 bapineuzumab subcutaneous (AAB-001) Janssen Alzheimer Immunotherapy South San Francisco, CA Pfi zer New York, NY Alzheimer’s disease (subcutaneous) Phase II (888) 381-4595 (800) 879-3477 BCI-632 BrainCells San Diego, CA Alzheimer’s disease Phase I (858) 812-7700 BCI-838 BrainCells San Diego, CA Alzheimer’s disease Phase I (858) 812-7700 BIIB037 (amyloid beta-protein inhibitor) Biogen Idec Cambridge, MA Alzheimer’s disease Phase I (617) 679-2000 bisnorcymserine (BNC) QR Pharma Berwyn, PA Alzheimer’s disease Phase I (610) 727-3913 BMS-241027 (microtubule stabilizer) Bristol-Myers Squibb Princeton, NJ Alzheimer’s disease, tauopathies Phase I (800) 332-2056 BMS-708163 (avagacestat) Bristol-Myers Squibb Princeton, NJ Alzheimer’s disease Phase II (800) 332-2056 BMS-932481 (gamma secretase modulator) Bristol-Myers Squibb Princeton, NJ Alzheimer’s disease Phase I (800) 332-2056 BMS-933043 (a-7 nicotinic agonist) Bristol-Myers Squibb Princeton, NJ cognitive impairment Phase I (800) 332-2056 CAD106 (amyloid beta-protein inhibitor) Novartis Pharmaceuticals East Hanover, NJ Alzheimer’s disease Phase II (888) 669-6682 CERE-110 (AAV-NGF gene therapy) Ceregene San Diego, CA Alzheimer’s disease Phase II (858) 458-8800 CHF-5074 (amyloid precursor protein secretase modulator) Chiesi Pharmaceuticals Rockville, MD mild cognitive impairment Phase II (301) 424-2661 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 crenezumab (anti-Abeta) Genentech South San Francisco, CA Alzheimer’s disease Phase II (800) 626-3553 CTS-21166 (ß-secretase inhibitor) Astellas Pharma US Deerfield, IL CoMentis South San Francisco, CA Alzheimer’s disease Phase I (800) 695-4321 (650) 359-2600 CX717 Cortex Pharmaceuticals Irvine, CA Alzheimer’s disease Phase II completed (949) 727-3157 davunetide intranasal Allon Therapeutics Vancouver, Canada Alzheimer’s disease, mild cognitive impairment Phase II (604) 736-0634 docosahexaenoic acid (DHA) Martek Biosciences Parsippany, NJ Alzheimer’s disease Phase III (973) 257-8011 DSP-8658 (PPAR a/g agonist) Sunovion Pharmaceuticals Marlborough, MA Alzheimer’s disease Phase I (508) 481-6700 E2212 (amyloid precursor protein secretase modulator) Eisai Woodcliff Lake, NJ Alzheimer’s disease Phase I (888) 274-2378 E2609 (BACE1 protein inhibitor) Eisai Woodcliff Lake, NJ Alzheimer’s disease Phase I (888) 274-2378 ELND005 (amyloid beta-protein inhibitor) Elan South San Francisco, CA Transition Therapeutics Toronto, Canada mild to moderate Alzheimer’s disease (Fast Track) Phase II (650) 877-0900 (416) 260-7770 EVP-0962 (amyloid precursor protein secretase modulator) EnVivo Pharmaceuticals Watertown, MA Alzheimer’s disease Phase I (617) 225-4250 EVP-6124 (α7-nAChR agonist) EnVivo Pharmaceuticals Watertown, MA mild to moderate Alzheimer’s disease Phase II (617) 225-4250 exebryl-1® ProteoTech Kirkland, WA Alzheimer’s disease Phase I (425) 823-0400 F18-florbetaben (molecular imaging agent) Piramal Healthcare Mumbai, India Alzheimer’s disease (diagnosis) Phase III www.piramalhealthcare.com F18-flutemetamol (PET imaging agent) GE Healthcare Waukesha, WI Alzheimer’s disease (diagnosis) Phase III www.gehealthcare.com Medicines in Development Alzheimer’s Disease 20126 Medicines in Development for Alzheimer’s Disease Alzheimer’s DiseAse AnD DementiAs product Name Sponsor Indication Development Status Gammagard® immune globulin intravenous (human), 10% solution Baxter Healthcare Deerfield, IL early-stage Alzheimer’s disease, mid-stage Alzheimer’s disease Phase III (800) 422-9837 gantenerumab (RG1450) Roche Nutley, NJ prodromal Alzheimer’s disease Phase II/III (973) 235-5000 GSK239512 GlaxoSmithKline Rsch. Triangle Park, NC Alzheimer’s disease Phase II completed (888) 825-5249 GSK742457 (5HT6 antagonist) GlaxoSmithKline Rsch. Triangle Park, NC Alzheimer’s disease Phase II completed (888) 825-5249 GSK933776A (anti-B amyloid mAb) GlaxoSmithKline Rsch. Triangle Park, NC Alzheimer’s disease Phase I completed (888) 825-5249 HPP-854 (BACE1 inhibitor) High Point Pharmaceuticals High Point, NC Alzheimer’s disease Phase I (336) 841-0300 human immunoglobulin (intravenous) Grifols USA Los Angeles, CA Alzheimer’s disease Phase III (888) 474-3657 immune globulin high dose Octapharma USA Hoboken, NJ Alzheimer’s disease (elderly) Phase II completed (201) 604-1130 irdabisant (CEP-26401) Cephalon Frazer, PA cognitive dysfunction associated with Alzheimer’s disease Phase I (610) 344-0200 LMTX (TRx-0237) TauRx Pharmaceuticals Singapore mild to moderate Alzheimer’s disease Phase I www.taurx.com LNK-754 Link Medicine Waltham, MA mild Alzheimer’s disease Phase I completed (781) 577-6700 LU AE58054 Lundbeck Deerfield, IL Alzheimer’s disease Phase II (800) 455-1141 MCD-386/glycopyrrolate Mithridion Madison, WI autosomal dominant Alzheimer’s disease Phase I www.mithridion.com MK-3134 Merck Whitehouse Station, NJ dementia Phase I completed (800) 672-6372 MK-3328 (PET tracer) Merck Whitehouse Station, NJ Alzheimer’s disease (diagnosis) Phase I completed (800) 672-6372 MK-8931 (BACE1 inhibitor) Merck Whitehouse Station, NJ Alzheimer’s disease Phase I (800) 672-6372 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 MSDC-0160 Metabolic Solutions Development Company Kalamazoo, MI Alzheimer’s disease Phase II (269) 343-6732 NIC5-15 Humanetics Minneapolis, MN Alzheimer’s disease Phase II (952) 937-7660 PF-05212377 (SAM-760) Pfizer New York, NY Alzheimer’s disease Phase I (800) 879-3477 pioglitazone companion diagnostic Takeda Pharmaceuticals U.S.A. Deerfield, IL Zinfadel Pharmaceuticals Chapel Hill, NC Alzheimer’s disease (diagnosis) Phase I (877) 825-3327 posiphen™ R-phenserine QR Pharma Berwyn, PA Alzheimer’s disease, mild cognitive impairment Phase II (610) 727-3913 PRX-3140 (5-HT4 partial agonist) Nanotherapeutics Alachua, FL Alzheimer’s disease Phase II (386) 462-9663 RG1577 (MAO-B inhibitor) Roche Nutley, NJ Alzheimer’s disease Phase II (973) 235-5000 RG1662 (GABAA a5 receptor modulator) Roche Nutley, NJ cognitive disorders Phase I (973) 235-5000 RG7129 (BACE1 protein inhibitor) Roche Nutley, NJ Alzheimer’s disease Phase I (973) 235-5000 rilapladib GlaxoSmithKline Rsch. Triangle Park, NC Human Genome Sciences Rockville, MD Alzheimer’s disease Phase II (888) 825-5249 (301) 309-8504 RVX-208 (BET protein inhibitor) Resverlogix Calgary, Canada Alzheimer’s disease Phase I (403) 254-9252 SAR110894 (H3 antagonist) Sanofi US Bridgewater, NJ Alzheimer’s disease Phase II (800) 981-2491 SAR228810 Sanofi US Bridgewater, NJ Alzheimer’s disease Phase I (800) 981-2491 sGC-1061 sGC Pharma Wellesley, MA Alzheimer’s disease Phase I (613) 791-4464 Medicines in Development Alzheimer’s Disease 20128 Medicines in Development for Alzheimer’s Disease Alzheimer’s DiseAse AnD DementiAs product Name Sponsor Indication Development Status solanezumab Eli Lilly Indianapolis, IN Alzheimer’s disease Phase III (800) 545-5979 ST-101 Sonexa Therapeutics San Diego, CA Alzheimer’s disease Phase II (858) 356-6250 SYN-120 Biotie Therapies South San Francisco, CA cognitive disorders associated with Alzheimer’s disease Phase I completed (650) 244-4850 T-817MA Toyama Chemical Tokyo, Japan mild to moderate Alzheimer’s disease Phase II completed www.toyama-chemical.co.jp TC-5619 Targacept Winston-Salem, NC Alzheimer’s disease Phase I (336) 480-2100 TD-8954 (5-HT4 agonist) Theravance South San Francisco, CA cognitive impairment associated with Alzheimer’s disease Phase I (877) 275-8479 TTP-448 (RAGE antagonist) TransTech Pharma High Point, NC Alzheimer’s disease Phase II (336) 841-0300 UB-311 (amyloid beta protein inhibitor vaccine) United Biomedical Hauppauge, NY mild to moderate Alzheimer’s disease Phase I (631) 273-2828 V950 vaccine Merck Whitehouse Station, NJ Alzheimer’s disease Phase I (800) 672-6372 vanutide cridificar (ACC-001) Janssen Alzheimer Immunotherapy South San Francisco, CA Pfizer New York, NY Alzheimer’s disease Phase II (888) 381-4595 (800) 879-3477 velusetrag (TD-5108) Theravance South San Francisco, CA Alzheimer’s disease Phase I (877) 275-8479 VI-1121 VIVUS Mountain View, CA Alzheimer’s disease Phase II (650) 934-5200 XEL 001HP (transdermal patch) Xel Pharmaceuticals Draper, UT Alzheimer’s disease Phase I (866) 832-7546 Medicines in Development Alzheimer’s Disease 2012 9 Glossary Alzheimer’s disease—The most common form of dementia, characterized by progressive and chronic deterioration of cognitive functions, including memory, thinking and reasoning. Early manifestations include forgetfulness, impaired ability to focus, and changes in mood and personality. As the disease progresses, there is a loss of computational ability, in addi- tion to word-finding problems and difficulty with ordinary activities. Ultimately, the disease leads to severe memory loss, complete disorienta- tion, social withdrawal, loss of independence, and is fatal. application submitted—An application for marketing approval has been submitted to the U.S. Food and Drug Administration (FDA). The application can either be an NDA (new drug application) or a BLA (biologic license application). cognitive disorders—Disorders of the higher mental processes, including understand- ing, reasoning, knowledge, and intellectual capacity. A person with a cognitive disorder, such as Alzheimer’s disease, does not process information correctly within the brain, resulting in impaired awareness and judgment, difficulty reasoning and focusing, loss of memory and abnormal mental capacity. People with cogni- tive disorders have problems acquiring, men- tally organizing and responding to information, which results in an inability to function normally in everyday life situations. dementia—Loss of mental ability that inter- feres with normal daily activities. It lasts more than six months, it not present at birth and is not associated with loss or altered conscious- ness. The natural decline of these functions with age is grossly exaggerated in dementia. Fast track—A U.S. Food and Drug Admin- istration (FDA) process designed to facilitate development and expedite the regulatory review of drugs to treat serious diseases and fill an unmet medical need. The purpose is to get new drugs for serious diseases to patients earlier and must be requested by the biophar- maceutical company. Fast Track addresses a broad range of serious diseases. Generally, determining factors include whether the drug will have an impact on such factors as survival, day-to-day functioning, or the likelihood that the disease, if left untreated, will progress from a less severe condition to a more serious one. Filling an unmet medical need is defined as providing a therapy where none exists or providing a therapy which may be potentially superior to existing therapy. Once a drug receives Fast Track designation, early and frequent communication between the FDA and a drug company is encouraged throughout the entire drug development and review process. The frequency of communication assures that questions and issues are resolved quickly, with the goal to achieve earlier drug approval and access by patients. mild Alzheimer’s disease—A stage of Al- zheimer’s disease characterized by a series of changes in cognitive abilities that may include, memory loss for recent events, difficulty with problem solving, changes in personality, dif- ficulty organizing and expressing thoughts, getting lost or misplacing belongings. This is the stage at which the disease is often first diagnosed. moderate Alzheimer’s disease—A stage of Alzheimer’s disease characterized by increased confusion, greater memory loss, sig- nificant changes in personality, and the need for assistance with basic daily activities. These changes are related to damage in areas of the brain that control language, reasoning, sensory processing, and conscious thinking. At this stage, patients may have problems recognizing family and friends, experience hallucinations, delusions, and paranoia, and may behave impulsively. pet imaging—Positron emission tomography (PET), a noninvasive medical imaging tech- nique that utilizes a radioactive agent (“tracer”) incorporated in a biologically active molecule and a scanner to produce three-dimensional images of the body. phase 0—First-in-human trials conducted in accordance with FDA’s 2006 guidance on exploratory Investigational New Drug (IND) studies designed to speed up development of promising drugs by establishing very early on whether the agent behaves in human subjects as was anticipated from preclinical studies. phase I—Researchers test the drug in a small group of people, usually between 20 and 80 healthy adult volunteers, to evaluate its initial safety and tolerability profile, determine a safe dosage range, and identify potential sid