美国1999年开发中的神经病新药

1999 Neurologic Disorders N E W 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 Survey 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 C O M P A N I E S As the “decade of the brain” draws to a close,pharmaceutical company researchers are closing in ontreatments for such diseases as Alzheimer’s, brain tumors, epilepsy, migraine headache, multiple sclerosis, pain, Parkinson’s disease, stroke and many others. Using new knowledge about how the brain works and what genes and proteins are involved in brain disorders, researchers are finding new ways to regrow damaged nerve cells, kill brain tumors, prevent cell death in stroke patients, lessen the severity of multiple sclerosis, and effectively treat other neurologic disorders. A new survey by the Pharmaceutical Research and Manufacturers of America (PhRMA) found 138 medicines in development for neurologic disorders by 89 companies—20 more medicines and 14 more companies than when the last survey was conducted. This stepped-up research comes on top of unprecedented recent progress on the neurological frontier. In just the past few years, pharmaceutical companies have brought to patients: • the first medicines approved for Alzheimer’s disease, which afflicts some 4 million Americans and costs the U.S. economy more than $100 billion a year • the first medicine shown to extend survival in people with ALS, or Lou Gehrig’s disease • a clot-busting medicine than can reduce the risk of permanent brain damage in stroke patients, potentially saving more than $100 million each year • new medicines to enhance the treatment of Parkinson’s disease, which affects one of every 100 people over age 60 • breakthrough medicines for migraine headaches that have helped reduce worker absenteeism and improve productivity • drugs that have dramatically improved the quality of life for people with multiple sclerosis, which affects some 350,000 Americans • a medicine shown to shrink tumors in people with treatment- resistant brain cancer Medicines currently in the pipeline—either in human clinical trials or awaiting approval by the Food and Drug Administration— include: 27 for brain tumors, 23 for Alzheimer’s disease, 17 for stroke, 16 for pain, 15 for Parkinson’s disease, 12 for multiple sclerosis, 11 for epilepsy, 10 for migraine headache, 5 for sleep disorders, and 4 each for head injury and ALS or Lou Gehrig’s disease. Many of the potential new medicines approach neurologic disorders in novel ways. These include: • Nerve-growth agents that target damaged nerves and prompt new cells to grow and reconnect with other neurons. These oral medicines, known as neuroimmunophillins, have been shown to successfully cross the blood/brain barrier and are being developed for spinal cord and head injuries, ALS, Parkinson’s disease, stroke, diabetic neuropathy, and Alzheimer’s disease. • A drug to treat various forms of cancer that may be able to help people with multiple sclerosis. In clinical trials, the drug significantly reduced the relapse rate and delayed progression of the disease in patients with secondary progressive multiple sclerosis. • An enzyme derived from the venom of the Malayan pit viper that shows promise in reversing the effects of stroke. • A medicine that reduces the buildup of lactic acid in the brain following head trauma, thus stopping the process that leads to cell death. These potential new medicines, and the ongoing research fueled by the pharmaceutical industry’s investment of an estimated $5.6 billion a year in research on diseases of the central nervous system, offer hope that some of the cruelest of human afflictions may finally be effectively treated. Alan F. Holmer President PhRMA Pharmaceutical Researchers from 89 Companies Are Testing 138 New Medicines to Help Patients with Brain Diseases 1999 MEDICINES IN DEVELOPMENT FOR NEUROLOGIC DISORDERS* Other Stroke Spinal Cord Injury Sleep Disorders Parkinson’s Disease Pain Neuropathies Multiple Sclerosis Migraine Headache Head Injury Epilepsy Brain Tumors Amyotrophic Lateral Sclerosis Alzheimer’s Disease 4 23 11 2 27 4 10 12 3 16 15 5 2 17 Huntington’s Disease 5 *Some medicines are listed in more than one category. 99265 Neuro.Disord NewStyle.cc 10/12/99 3:20 PM Page 1 2 N E W 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 Neurologic Disorders 1999 New Medicines in Development for Neurologic Disorders A L Z H E I M E R ’ S D I S E A S E Product Name Company Indication Development Status ALCAR Sigma-Tau Pharmaceuticals Phase III acetyl-l-carnitine Gaithersburg, MD HCl Ampalex™ Cortex Pharmaceuticals Phase II CX516 Irvine, CA AN-1792 Elan Pharmaceuticals Phase I S. San Francisco, CA Aricept® Eisai dementia with Phase III donepezil HCI Teaneck, NJ cerebrovascular disease Celebrex Pfizer (see also pain) Phase II celecoxib New York, NY Searle (Monsanto) Skokie, IL DP 543 Du Pont Pharmaceuticals Phase II Wilmington, DE Exelon™ Novartis Pharmaceuticals application submitted rivastigmine East Hanover, NJ idebenone Takeda America Phase II/III R&D Center Princeton, NJ memantine Neurobiological (see also neuropathies, other) Phase III Technologies Richmond, CA Merz Frankfurt, Germany metrifonate Bayer, Pharmaceutical primary degenerative dementia application submitted Division West Haven, CT Neotrofin™ NeoTherapeutics Phase II leteprinim Irvine, CA potassium (AIT-082) Premarin® Wyeth-Ayerst Laboratories Phase III conjugated Philadelphia, PA estrogens tablets Premphase® Wyeth-Ayerst Laboratories Phase III conjugated Philadelphia, PA estrogens,medroxy- progesterone acetate tablets Prempro™ Wyeth-Ayerst Laboratories Phase III conjugated Philadelphia, PA estrogens/medroxy- progesterone acetate tablets 99265 Neuro.Disord NewStyle.cc 10/12/99 3:20 PM Page 2 3N E W 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 Neurologic Disorders 1999 A L Z H E I M E R ’ S D I S E A S E Product Name Company Indication Development Status propentofylline Hoechst Marion Roussel Alzheimer’s disease Phase III Kansas City, MO and vascular dementia Reminyl® Janssen Pharmaceutica Phase III galantamine Titusville, NJ SL 65,0102 Sanofi-Synthelabo Phase II New York, NY SR 141716 Sanofi-Synthelabo Phase II New York, NY SR 57746 Sanofi-Synthelabo (see also amyotrophic Phase II New York, NY lateral sclerosis) Synapton Forest Laboratories application submitted physostigmine New York, NY extended-release tablets talsaclidine Boehringer Ingelheim Phase II Pharmaceuticals Ridgefield, CT Tempium™ Hoffmann-La Roche Phase III lazabemide Nutley, NJ Vioxx® Merck prevention and treatment Phase III rofecoxib Whitehouse Station, NJ A M Y O T R O P H I C L A T E R A L S C L E R O S I S ( A L S ; L O U G E H R I G ’ S D I S E A S E ) Product Name Company Indication Development Status brain-derived Amgen Phase I/II neurotrophic Thousand Oaks, CA factor (BDNF) Regeneron Pharmaceuticals Tarrytown, NY Myotrophin® Cephalon application submitted mecasermin West Chester, PA (Orphan Drug) Chiron Emeryville, CA Neurontin Warner-Lambert in clinical trials gabapentin Morris Plains, NJ SR 57746 Sanofi-Synthelabo (see also Alzheimer’s disease) Phase II New York, NY B R A I N T U M O R S Product Name Company Indication Development Status adenoviral p53 Introgen Therapeutics Phase I Austin, TX N C I T R I A L Rhone-Poulenc Rorer Collegeville, PA National Cancer Institute Bethesda, MD alanosine Triangle Pharmaceuticals glioma Phase II Durham, NC 99265 Neuro.Disord NewStyle.cc 10/12/99 3:20 PM Page 3 4 N E W 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 Neurologic Disorders 1999 B R A I N T U M O R S Product Name Company Indication Development Status allogeneic glioma Immune Response newly diagnosed glioblastoma Phase I cancer vaccine Carlsbad, CA multiforme or anaplastic astrocytoma Avonex® Biogen glioma Phase II interferon beta-1a Cambridge, MA (see also multiple sclerosis, other) (Orphan Drug) Cereport™ Alkermes metastatic brain tumor Phase II and carboplatin Cambridge, MA recurrent malignant glioma Phase II pediatric brain tumor Phase I/II chimeric MAb National Cancer Institute brain cancer Phase II 14.18 Bethesda, MD N C I T R I A L CI-980 National Cancer Institute brain cancer Phase I/II Bethesda, MD N C I T R I A L Warner-Lambert Morris Plains, NJ Cotara Techniclone anaplastic astrocytoma, malignant Phase II New York, NY glioma, newly-formed glioma gallium nitrate National Cancer Institute brain cancer Phase II Bethesda, MD N C I T R I A L Gliadel® Wafer Guilford Pharmaceuticals glioblastoma multiforme Phase III (Orphan Drug) Baltimore, MD at initial surgery Rhone-Poulenc Rorer Collegeville, PA Gliadel® Wafer Guilford Pharmaceuticals recurrent malignant glioma Phase II (high dose) Baltimore, MD (Orphan Drug) Rhone-Poulenc Rorer Collegeville, PA IL 13-PE38QQR Neopharm malignant glioma Phase I/II Lake Forest, IL IUDR National Cancer Institute brain cancer Phase I Bethesda, MD N C I T R I A L Neopharm Lake Forest, IL IV hydroxyurea National Cancer Institute brain cancer Phase II Bethesda, MD N C I T R I A L Bristol-Myers Squibb Princeton, NJ mitalactol Feminique Phase III Bellport, NY n-acyl- Dekk-Tec childhood gliomas Phase I penclomedines New Orleans, LA NBI-3001 Neurocrine Biosciences glioblastoma Phase II (IL-4 fusion toxin) San Diego, CA phenylacetate National Cancer Institute brain cancer Phase II Bethesda, MD N C I T R I A L Elan Pharmaceuticals S. San Francisco, CA 99265 Neuro.Disord NewStyle.cc 10/12/99 3:20 PM Page 4 5N E W 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 Neurologic Disorders 1999 B R A I N T U M O R S Product Name Company Indication Development Status phenylbutyrate National Cancer Institute brain cancer Phase I/II Bethesda, MD N C I T R I A L Elan Pharmaceuticals S. San Francisco, CA RSR-13 Allos Therapeutics brain metastases from primary Phase II Denver, CO breast cancer rubitecan SuperGen Phase II San Ramon, CA SU101 SUGEN malignant glioma Phase III S. San Francisco, CA temozolomide National Cancer Institute brain cancer Phase II Bethesda, MD N C I T R I A L Thalomid™ National Cancer Institute glioblastoma Phase II thalidomide Bethesda, MD N C I T R I A L Celgene Warren, NJ Tirazone™ Sanofi-Synthelabo Phase II tirapazamine New York, NY trans-retinoic acid National Cancer Institute glioma Phase II Bethesda, MD N C I T R I A L Xcytrin™ Pharmacyclics brain metastases Phase III Sunnyvale, CA E P I L E P S Y Product Name Company Indication Development Status ganaxolone CoCenesys (see also migraine headache) Phase II Irvine, CA GKE-841 Wyeth-Ayerst Laboratories Phase II Philadelphia, PA NeuroCell™-FE Diacrin Phase I Charlestown, MA oxcarbazepine Novartis Pharmaceuticals application submitted East Hanover, NJ pregabalin Warner-Lambert (see also pain) Phase II/III Morris Plains, NJ remacemide HCI AstraZeneca (see also Huntington’s disease, Phase II Wilmington, DE Parkinson’s disease) rufinamide Novartis Pharmaceuticals epilepsy deterrent Phase III East Hanover, NJ Topamax R.W. Johnson Lennox-Gastaut syndrome, Phase III topiramate Pharmaceutical Research monotherapy in partial onset Institute seizures, pediatric partial onset Raritan, NJ seizures, tonic/clonic seizures (see also migraine headache, pain) vigabatrin Hoechst Marion Roussel application submitted Kansas City, MO 99265 Neuro.Disord NewStyle.cc 10/12/99 3:20 PM Page 5 6 N E W 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 Neurologic Disorders 1999 E P I L E P S Y Product Name Company Indication Development Status YKP 509 SK Biopharmaceutical Phase I Fairfield, NJ Zonegran™ Elan Pharmaceuticals simple and complex partial seizures application submitted zonisamide S. San Francisco, CA H E A D I N J U R Y Product Name Company Indication Development Status Ceresine™ Cypros Pharmaceutical traumatic brain injury Phase II completed Carlsbad, CA (see also stroke) CP-101,606 Pfizer traumatic brain injury Phase II New York, NY NPS 1506 NPS Pharmaceuticals head trauma Phase I Salt Lake City, UT (see also stroke) ziconotide Elan Pharmaceuticals (see also pain) Phase II (SNX-111) S. San Francisco, CA H U N T I N G T O N ’ S D I S E A S E Product Name Company Indication Development Status NeuroCell™-HD Diacrin Huntington’s disease Phase I (Orphan Drug) Charlestown, MA Genzyme Cambridge, MA remacemide HCI AstraZeneca (see also epilepsy, Parkinson’s Phase III Wilmington, DE disease) M I G R A I N E H E A D A C H E Product Name Company Indication Development Status 4991W93 Glaxo Wellcome Phase I Rsch. Triangle Park, NC almotriptan Pharmacia & Upjohn Phase III (Orphan Drug) Peapack, NJ ALX-0646 Allelix Biopharmaceuticals Phase I/II Mississauga, Ontario Depakote® ER Abbott Laboratories migraine prophylaxis application submitted divalproex sodium Abbott Park, IL (extended release) frovatriptan Elan Pharmaceuticals application submitted S. San Francisco, CA ganaxolone CoCenesys migraine prophylaxis Phase II Irvine, CA (see also epilepsy) GW419458 Glaxo Wellcome Phase I Rsch. Triangle Park, NC Relpax Pfizer application submitted New York, NY SB220453 SmithKline Beecham Phase II Philadelphia, PA 99265 Neuro.Disord NewStyle.cc 10/12/99 3:20 PM Page 6 7N E W 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 Neurologic Disorders 1999 M I G R A I N E H E A D A C H E Product Name Company Indication Development Status topiramate R.W. Johnson (see also epilepsy, pain) Phase II Pharmaceutical Research Institute Raritan, NJ M U L T I P L E S C L E R O S I S Product Name Company Indication Development Status Antegren® Elan Pharmaceuticals chronic multiple sclerosis Phase II S. San Francisco, CA ATM-027 AstraZeneca Phase I Wilmington, DE Avant ImmunoTherapeutics Needham, MA Avonex® Biogen monosymptomatic multiple Phase III interferon beta-1a Cambridge, MA sclerosis, secondary progressive (Orphan Drug) multiple sclerosis (see also brain tumors, other) Betaseron® Berlex Laboratories secondary progressive application submitted interferon beta-1b Montville, NJ multiple sclerosis Chiron Emeryville, CA Copaxone® TEVA Pharmaceuticals USA primary progressive Phase III copolymer-1 Kulpsville, PA multiple sclerosis IR-208 Immune Response Phase I Carlsbad, CA LeukArrest™ ICOS (see also stroke) Phase II Bothell, WA MSP-771 Neurocrine Biosciences Phase II San Diego, CA Novantrone® Immunex secondary progressive application submitted mitoxantrone Seattle, WA multiple sclerosis for injection concentrate Provigil® Cephalon (see also sleep disorders) Phase II modafinil West Chester, PA Rebif® Serono Laboratories relapsing-remitting multiple sclerosis application submitted human interferon Norwell, MA beta 1-a early treatment of multiple sclerosis Phase III secondary progressive multiple sclerosis Phase III thalidomide Andrulis Pharmaceuticals Phase II (Orphan Drug) Bethesda, MD N E U R O P A T H I E S Product Name Company Indication Development Status memantine Neurobiological painful diabetic neuropathy Phase II Technologies (see also Alzheimer’s disease, other) Richmond, CA 99265 Neuro.Disord NewStyle.cc 10/12/99 3:20 PM Page 7 8 N E W 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 Neurologic Disorders 1999 N E U R O P A T H I E S Product Name Company Indication Development Status Symlin™ Amylin Pharmaceuticals diabetic neuropathy Phase III pramlintide acetate San Diego, CA timcodar dimesylate Vertex Pharmaceuticals diabetic neuropathy Phase II Cambridge, MA P A I N Product Name Company Indication Development Status ABT-594 Abbott Laboratories Phase II Abbott Park, IL Celebrex Pfizer chronic pain Phase III celecoxib New York, NY (see also Alzheimer’s disease) Searle (Monsanto) Skokie, IL depomorphine SkyePharma acute post-operative pain Phase II San Diego, CA (epidermal) MK-663 Merck Phase II Whitehouse Station, NJ Morphelan™ Elan Pharmaceuticals moderate to severe chronic pain Phase III morphine S. San Francisco, CA (sustained-release) Ligand Pharmaceuticals San Diego, CA neural cells Diacrin chronic pain subsequent to Phase I Charlestown, MA spinal cord injury oxycodine/ Forest Laboratories post-surgical pain Phase III ibuprofen New York, NY parecoxib Searle (Monsanto) pain management Phase III Skokie, IL pregabalin Warner-Lambert (see also epilepsy) Phase II/III Morris Plains, NJ RWJ 57504 R.W. Johnson Phase II Pharmaceutical Research Institute Raritan, NJ SR 48968 Sanofi-Synthelabo Phase II New York, NY Stanamet™ Diatide bone pain in cancer patients Phase II Londonderry, NH topiramate R.W. Johnson neuropathic pain Phase II Pharmaceutical (see also epilepsy, migraine Research Institute headache) Raritan, NJ valdecoxib Pfizer chronic pain Phase III New York, NY Searle (Monsanto) Skokie, IL ZD6416 AstraZeneca acute and chronic pain Phase II Wilmington, DE 99265 Neuro.Disord NewStyle.cc 10/12/99 3:20 PM Page 8 9N E W 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 Neurologic Disorders 1999 P A I N Product Name Company Indication Development Status ziconotide Elan Pharmaceuticals (see also head injury) Phase III (SNX-111) S. San Francisco, CA P A R K I N S O N ’ S D I S E A S E Product Name Company Indication Development Status Altropane™ Boston Life Sciences imaging agent for early to mild Phase III Boston, MA Parkinson’s disease and other movement disorders apomorphine HCl Pentech Pharmaceuticals Phase III sublingual tablets Wheeling, IL (Orphan Drug) Dopascan™ Guilford Pharmaceuticals Phase II completed Injection Baltimore, MD DU-127090 Solvay Pharmaceuticals Phase II Marietta, GA NeuroCell™-PD Diacrin Phase II (Orphan Drug) Charlestown, MA Genzyme Cambridge, MA NIL-A Amgen Phase I Thousand Oaks, CA Guilford Pharmaceuticals Baltimore, MD PNU 95666E Pharmacia & Upjohn Phase II (Orphan Drug) Peapack, NJ remacemide HCI AstraZeneca (see also epilepsy, Huntington’s Phase II Wilmington, DE disease) Rilutek® Rhone-Poulenc Rorer Phase III riluzole Collegeville, PA SIB-1508Y; SIBIA Neurosciences Phase II altinicline La Jolla, CA Spheramine™ Titan Pharmaceuticals Phase I/II allogeneic human S. San Francisco, CA retinal pigment epithelial cells on gelatin microcarriers (Orphan Drug) SPM 962 Schwarz Pharma Phase II (transdermal patch) Milwaukee, WI Sygen® Fidia Pharmaceutical (see also spinal cord injury) Phase III monosialogan- Washington, DC glioside GM1 TV-1012 TEVA Pharmaceuticals USA Phase III Kulpsville, PA TV-1203 TEVA Pharmaceuticals USA Phase III Kulpsville, PA 99265 Neuro.Disord NewStyle.cc 10/12/99 3:20 PM Page 9 10 N E W 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 Neurologic Disorders 1999 S L E E P D I S O R D E R S Product Name Company Indication Development Status CCD-3693 CoCenesys insomnia Phase I Irvine, CA NBI-34060 Neurocrine Biosciences insomnia Phase II San Diego, CA Provigil® Cephalon sleepiness or fatigue in sleep apnea Phase II modafinil West Chester, PA (see also multiple sclerosis) SR 46349 Sanofi-Synthelabo Phase II New York, NY Xyrem™ Orphan Medical narcolepsy Phase III sodium oxybate Minnetonka, MN (Orphan Drug) S P I N A L C O R D I N J U R Y Product Name Company Indication Development Status CM101 Carbomed acute spinal cord injury Phase I Brentwood, TN Sygen® Fidia Pharmaceutical acute spinal cord injury Phase III monosialogan- Washington, DC (see also Parkinson’s disease) glioside GM1 S T R O K E Product Name Company Indication Development Status aptiganel Cambridge Neuroscience Phase II completed (CNS 1102) Cambridge, MA Arvin® Knoll Pharmaceutical Phase III ancrod Mt. Olive, NJ BMS 204352 Bristol-Myers Squibb acute stroke Phase II Princeton, NJ Ceresine™ Cypros Pharmaceutical ischemic stroke Phase II completed Carlsbad, CA (see also head injury) Cervene® Baker Norton Phase III nalmefene Pharmaceuticals HCI Miami, FL citicoline Interneuron ischemic stroke Phase III Pharmaceuticals Lexington,