美国2000年开发中的生物技术新药

By using the body’s own tools and weapons to fight disease,pharmaceutical and biotechnology companies aredeveloping more and better medicines. A survey by the Pharmaceutical Research and Manufacturers of America (PhRMA) found 369 medicines in the pipeline that meet the definition of “biotechnology medicines”: they use proteins and other substances produced in the human body to counter disease. All together, the biotechnology medicines in the pipeline target more than 200 diseases. Nearly half the medicines—175—are for cancer, the second leading killer of Americans. Biotechnology and new technologi- cal tools have revolutionized cancer research. Said Dr. Harmon Eyre of the American Cancer Society: “In the past, we could look under the microscope and say a cell looks abnormal, but we didn’t know what was going on inside it.” Now, in some cases, said Dr. Eyre, you can find the genetic defects and attack them— with immune therapies, growth inhibitors or drugs—in a way that is totally different. One of the new and different ways to attack cancer is with monoclonal antibodies. Antibodies are proteins made by the body’s immune system to bind to and neutralize foreign invaders. Monoclonal antibodies are created in the laboratory to do the same thing. These antibodies are already being used to fight breast cancer and non-Hodgkin’s lymphoma and are in testing for other kinds of cancer. For example, a potential medicine for colorectal cancer and non-small-cell lung cancer binds to a protein that pro- motes the growth of the blood vessels tumors need. The medicine prevents the protein from working, thereby starving the tumors of the blood they need to survive. Another new way to fight cancer is with vaccines designed to jump-start a patient’s natural defenses against disease. For example, a potential treatment for prostate cancer collects a patient’s own dendritic cells—immune system watchdogs that repel foreign invaders—then uses the cells in a cancer-fighting vaccine. Infectious diseases, such as hepatitis, genital herpes, urinary tract infections, sepsis and others, are the focus of 39 of the research projects. One of the medicines, for example, shows promise in treating patients with hepatitis C who also have cir- rhosis of the liver. The medicine is an interferon—a protein that interferes with the ability of a virus to reproduce after it invades the body. In this case, the protein has been altered to prevent it from being eliminated from the body too rapidly, enabling it to suppress the virus longer. Nineteen medicines target autoimmune diseases, including rheumatoid arthritis and scleroderma—a serious, sometimes life- threatening disease that affects some 100,000 Americans, mainly women. No effective treatment exists for the hardening of the skin and organs in this disease, but a medicine now in clinical trials shows promise. It’s a genetically engineered version of a protein that decreases the synthesis of new connective tissue. Other biotechnology medicines are in testing for heart disease, asthma, multiple sclerosis, arthritis, Alzheimer’s disease, AIDS, hemophilia, sickle cell anemia, diabetes, Crohn’s disease, inflam- matory bowel disorders, cystic fibrosis, and other diseases. As we enter what has been called “the century of biology,” the promise of breakthroughs on the biotechnology frontier is bright. Scientists have the technology to create new and better drugs by increasing the number of targets at which to aim. Said Dr. George Poste, a distinguished pharmaceutical researcher: “Companies have gone from having so few targets, which were guarded like Fort Knox, to being awash in targets.” As pharmaceutical companies take aim at those targets, there is increasing hope that the “century of biology” will also be the “century of cures.” Alan F. Holmer President and CEO PhRMA B I O T E C H N O L O G Y M E D I C I N E S I N D E V E L O P M E N T — B Y T H E R A P E U T I C C A T E G O R Y * 2000 Biotechnology 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 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 The Century of Biology Begins with 369 Biotechnology Medicines in Testing for More Than 200 Diseases Other Transplantation Skin Disorders Respiratory Diseases Neurologic Disorders Infertility Infectious Diseases Heart Disease Growth Disorders Genetic Disorders Eye Conditions Digestive Disorders Diabetes/Related Conditions Cancer/Related Conditions Blood Disorders Autoimmune Disorders AIDS/HIV Infection/Related Disorders 19 19 9 175 7 11 3 11 3 26 39 5 28 22 19 13 29 *Some medicines are l is ted in more than one category. 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 Biotechnology 2000 Biotechnology Medicines in Development A I D S / H I V I N F E C T I O N A N D R E L A T E D C O N D I T I O N S Product Product Development Name Company Category Indication Status Alferon N Interferon Sciences interferon HIV infection Phase III Injection® New Brunswick, NJ (see also infectious diseases) interferon alfa-n3 ------------------------------------------------------------------------- co-infection (HIV/HCV) Phase II ALVAC-MN Aventis Pasteur vaccine HIV infection Phase II 12-TMG Lyons, France (vCP205) Virogenetics Albany, NY Ampligen® Hemispherx Biopharma interferon HIV infection Phase II New York, NY (see also cancer, infectious diseases, other) autologous gene- SyStemix gene therapy HIV infection Phase I/II modified Palo Alto, CA hematopoietic stem cells GEM® 92 Hybridon antisense HIV infection/AIDS Phase I Milford, MA HE-2000 Hollis-Eden Pharmaceuticals cellular HIV infection, AIDS Phase I/II San Diego, CA therapy HIV vaccine Merck vaccine treatment and prevention of Phase I Whitehouse Station, NJ HIV infection/AIDS Immunokine OXO Chemie immune-based late-stage AIDS Phase III WF10 San Francisco, CA therapy ISIS 2922 Isis Pharmaceuticals antisense cytomegalovirus retinitis Phase III fomivirsen Carlsbad, CA PRO 367 Progenics Pharmaceuticals HIV infection Phase I Tarrytown, NY PRO 542 Progenics Pharmaceuticals HIV infection Phase I/II Tarrytown, NY Proleukin® Chiron interleukin HIV infection Phase III aldesleukin Emeryville, CA (see also cancer) (interleukin-2) Remune Agouron Pharmaceuticals immune- HIV seropositive Phase III HIV-1 immunogen LaJolla, CA based Immune Response therapy Carlsbad, CA REV123 Novartis Pharmaceuticals cellular HIV infection Phase I/II (gene-modified East Hanover, NJ therapy autologous cellular therapy) rgp120 VaxGen vaccine protection against HIV infection Phase III vaccine S. San Francisco, CA Savvy® Biosyn microbicide prevention of HIV infection Phase I C31G 1.2% Philadelphia, PA (see also infectious diseases, other) vaginal gel A I D S / H I V I N F E C T I O N A N D R E L A T E D C O N D I T I O N S Product Product Development Name Company Category Indication Status SU5416 SUGEN angiogenesis Kaposi’s sarcoma Phase II Redwood City, CA inhibitor (see also cancer) TBC-3B Therion Biologics vaccine AIDS prevention Phase I (vaccinia virus Cambridge, MA expressing HIV genes env, gag and pal) tenofovir disoproxil Gilead Sciences nucleotide HIV infection, AIDS Phase III fumarate Foster City, CA analogue (oral PMPA) A U T O I M M U N E D I S O R D E R S Product Product Development Name Company Category Indication Status Actimmune® InterMune Pharmaceuticals interferon idiopathic pulmonary fibrosis Phase II/III interferon gamma-1b Palo Alto, CA (see also infectious diseases) AnergiX.RA™ Corixa functional rheumatoid arthritis Phase I Seattle, WA antigenics immuno- therapy AnervaX.RA™ Corixa peptide rheumatoid arthritis Phase II Seattle, WA vaccine completed anti-CD40 antibody Bristol-Myers Squibb immune-based rheumatoid arthritis Phase I Princeton, NJ therapy Avonex® Biogen interferon idiopathic pulmonary fibrosis Phase II interferon beta-1a Cambridge, MA (see also cancer, neurologic) clenoliximab/ IDEC Pharmaceuticals MAb rheumatoid arthritis Phase II IDEC-151 San Diego, CA ConXn® Connetics recombinant scleroderma Phase II/III recombinant Palo Alto, CA human human relaxin protein Enbrel® Immunex recombinant disease modification of active application etanercept Seattle, WA soluble rheumatoid arthritis submitted Wyeth-Ayerst Laboratories receptor (see also heart, skin) Philadelphia, PA ------------------------------------------------------------------------- psoriatic arthritis Phase III h5G1.1 Alexion Pharmaceuticals MAb membranous nephritis, Phase II New Haven, CT rheumatoid arthritis (see also skin) ------------------------------------------------------------------------- lupus Phase I/II IDEC-131/MAb IDEC Pharmaceuticals MAb systemic lupus erythematosus Phase II gp39 CD4OL San Diego, CA IR 501 Immune Response vaccine rheumatoid arthritis Phase II therapeutic vaccine Carlsbad, CA Kineret Amgen recombinant rheumatoid arthritis application interleukin-1 receptor Thousand Oaks, CA protein submitted antagonist (IL-1ra) 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 Biotechnology 2000 A U T O I M M U N E D I S O R D E R S Product Product Development Name Company Category Indication Status MDX-33 Medarex MAb autoimmune diseases, idiopathic Phase II Annandale, NJ thrombocytopenic purpura Ontak® Ligand Pharmaceuticals fusion protein severe rheumatoid arthritis Phase I/II denileukin diftitox San Diego, CA (see also cancer, skin) ORTHOCLONE Ortho Biotech MAb treatment of CD4-mediated Phase II OKT4A Raritan, NJ autoimmune diseases (see also transplantation) recombinant human Serono Laboratories rheumatoid arthritis Phase II tumor necrosis Norwell, MA (see also digestive, heart) factor-binding protein 1 (rhTBP-1) soluble tumor Amgen recombinant rheumatoid arthritis Phase II necrosis factor-a Thousand Oaks, CA protein receptor type 1 (STNF-R1) Tenovil Schering-Plough interleukin rheumatoid arthritis Phase III interleukin-10 Madison, NJ (see also digestive, heart, infectious (IL-10) diseases, respiratory, skin) Veldona® Amarillo Biosciences interferon Sjogren’s syndrome Phase III natural human Amarillo, TX ------------------------------------------------------------------------- interferon-alpha fibromyalgia syndrome Phase II B L O O D D I S O R D E R S Product Product Development Name Company Category Indication Status AAV Avigen gene therapy hemophilia B Phase I Alameda, CA chimeric bone Chimeric Therapies cellular sickle cell disease Phase I/III marrow cell graft Laguna Niguel, CA therapy (see also cancer) CPC-111 Questcor Pharmaceutical cellular sickle cell disease Phase II Hayward, CA therapy factor VIII Transkaryotic Therapies gene therapy hemophilia A Phase I Cambridge, MA GA-EPO™ Transkaryotic Therapies erythropoietin anemia associated with Phase III gene-activated™ Cambridge, MA renal disease, anemia associated with erythropoietin cancer chemotherapy Kogenate-FS Bayer clotting hemophilia A application rFVIII Berkeley, CA factor submitted novel erythropoiesis Amgen recombinant stimulates the production of red application stimulating protein Thousand Oaks, CA protein blood cells for treatment of anemia submitted (NESP) in chronic renal failure patients ------------------------------------------------------------------------- stimulates the production of red Phase I blood cells for treatment of anemia in cancer patients 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 Biotechnology 2000 B L O O D D I S O R D E R S Product Product Development Name Company Category Indication Status ReFacto® Genetics Institute clotting hemophilia A application recombinant factor Cambridge, MA factor submitted VIII Wyeth-Ayerst Laboratories Philadelphia, PA YM-337 Yamanouchi USA MAb platelet aggregation Phase II White Plains, NY Protein Design Labs Fremont, CA C A N C E R A N D R E L A T E D C O N D I T I O N S Product Product Development Name Company Category Indication Status γ-fowlpox gp100: National Cancer Institute vaccine metastatic melanoma Phase I 209-217 (210M) Bethesda, MD N C I T R I A L Therion Biologics Cambridge, MA γ-fowlpox PSA National Cancer Institute vaccine prostate cancer Phase II vaccine Bethesda, MD N C I T R I A L Therion Biologics Cambridge, MA γ-vaccinia/γ-fowlpox National Cancer Institute vaccine melanoma Phase I B7.1 vaccine Bethesda, MD N C I T R I A L Therion Biologics Cambridge, MA γ-vaccinia/γ-fowlpox National Cancer Institute vaccine metastatic melanoma Phase II tyrosinase vaccine Bethesda, MD N C I T R I A L Therion Biologics Cambridge, MA γ-vaccinia MUC1 National Cancer Institute vaccine breast cancer Phase I vaccine Bethesda, MD N C I T R I A L Therion Biologics Cambridge, MA γ-vaccinia PSA National Cancer Institute vaccine prostate cancer Phase I/II vaccine Bethesda, MD N C I T R I A L Therion Biologics Cambridge, MA Aastrom™ Aastrom Biosciences cellular blood and immune system Phase II/III Cell Production Ann Arbor, MI therapy recovery in cancer patients System following chemotherapy stem and progenitor ablation/suppression cell expansion from bone marrow and umbilical cord blood abarelix Amgen peptide prostate cancer Phase III Thousand Oaks, CA antagonist (see also other) ABX-EGF Abgenix MAb colorectal, lung, prostate, Phase I Fremont, CA renal cancers 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 Biotechnology 2000 C A N C E R A N D R E L A T E D C O N D I T I O N S Product Product Development Name Company Category Indication Status adenovirus p53 National Cancer Institute gene bladder, breast, lung, ovarian Phase I Bethesda, MD therapy cancers, glioma N C I T R I A L Gencell Collegeville, PA Introgen Therapeutics Austin, TX AFP-Scan™ Immunomedics MAb, Fab´ location and extent of disease staging Phase II technetium-99m- Morris Plains, NJ fragment of liver and germ cell cancers FAb´ fragment (germ cell) allogeneic glioma Immune Response vaccine newly diagnosed glioblastoma Phase I cancer vaccine Carlsbad, CA multiforme or anaplastic astrocytoma Allomune™ BioTransplant humanized refractory non-Hodgkin’s Phase I humanized Charlestown, MA MAb lymphoma or Hodgkin’s disease anti-CD2 MAb Allovectin-7® Vical gene therapy advanced metastatic melanoma, Phase III DNA/lipid complex San Diego, CA non-resectable squamous cell encoding HLA-B7 carcinoma of the head and neck antigen ALVAC-B7.1 National Cancer Institute gene therapy melanoma Phase I Bethesda, MD N C I T R I A L ALVAC-B7.1 National Cancer Institute vaccine ovarian cancer Phase I vaccine with Bethesda, MD N C I T R I A L StemSep® ALVAC-CEA-B7.1 National Cancer Institute gene therapy advanced adenocarcinomas Phase I Bethesda, MD N C I T R I A L ALVAC-CEA National Cancer Institute vaccine advanced cancers Phase I vaccine Bethesda, MD N C I T R I A L ALVAC-IL-12 National Cancer Institute vaccine melanoma Phase I vaccine Bethesda, MD N C I T R I A L Aventis Pasteur Lyons, France Ampligen® Hemispherx Biopharma interferon renal cancer Phase I/II New York, NY (see also AIDS/HIV, infectious diseases, other) anhydrovinblastine IGT Pharma cytotoxic non-small-cell lung cancer Phase I (AVLB) Vancouver, British Columbia anti-gastrin Aphton vaccine colorectal, pancreatic, stomach Phase III therapeutic vaccine, Miami, FL cancers neutralizes Aventis Pasteur ------------------------------------------------------------------------- hormones G17 & Swiftwater, PA esophageal, liver cancers Phase II gly-extended G17 completed anti-Tac(Fv)-PE38 National Cancer Institute MAb+toxin leukemia, lymphoma Phase I immunotoxin Bethesda, MD N C I T R I A L anti-transferrin National Cancer Institute MAb advanced, refractory solid tumors Phase I receptor Bethesda, MD N C I T R I A L MAb 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 Biotechnology 2000 C A N C E R A N D R E L A T E D C O N D I T I O N S Product Product Development Name Company Category Indication Status anti-VEGF Genentech MAb metastatic non-small-cell lung, Phase III S. San Francisco, CA colorectal cancers APC 8015 Dendreon vaccine prostate cancer Phase III immune-based Seattle, WA therapy APC 8020 Dendreon vaccine multiple myeloma Phase II immune-based Seattle, WA therapy Apra™ Cell Therapeutics prostate cancer, Phase II (CT-2584) Seattle, WA soft tissue sarcoma Aptosyn™ Cell Pathways adenomatous polyosis coli application exisulind Horsham, MA submitted arsenic trioxide Cell Therapeutics leukemia Phase III (ATO) Seattle, WA completed Avonex® Biogen interferon glioma Phase II interferon beta-1A Cambridge, MA (see also autoimmune, neurologic) Avrend™ Immunex metastatic renal cell carcinoma Phase II CD40 ligand Seattle, WA ------------------------------------------------------------------------- epithelial solid tumors Phase I B7 transfected National Cancer Institute vaccine melanoma Phase I allogeneic Bethesda, MD N C I T R I A L melanoma cell vaccine Bexxar™ Coulter Pharmaceutical radio- low-grade and transformed Phase III tositumomab, iodine S. San Francisco, CA immunotherapy low-grade non-Hodgkin’s lymphoma I 131 tositumomab SmithKline Beecham Philadelphia, PA BrevaRex™ AltaRex MAb breast cancer, multiple myeloma, Phase I antibody-based Waltham, MA MUC1-expressing tumors immunotherapy CA4P OXiGENE angiogenesis advanced cancer, solid tumors Phase I/II Boston, MA inhibitor Campath® Millennium Pharmaceuticals MAb chronic lymphocytic leukemia application alemtuzumab Cambridge, MA (see also neurologic, transplantation) submitted CaPVax Northwest Biotherapeutics cellular prostate cancer Phase I (DC1/HRPC) Seattle, WA therapy carcinoembryonic National Cancer Institute vaccine breast, gastrointestinal tract, Phase I antigen peptide-1 Bethesda, MD lung cancers N C I T R I A L vaccine CEACide™ Immunomedics MAb colorectal cancer Phase I/II humanized Morris Plains, NJ anti-CEA antibody (hMN14) CEA-Scan™ Immunomedics MAb, Fab´ location and extent of disease staging Phase II technetium-99m- Morris Plains, NJ fragment of breast cancer arcitumomab (breast) 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 Biotechnology 2000 C A N C E R A N D R E L A T E D C O N D I T I O N S Product Product Development Name Company Category Indication Status CEA-Scan™ Immunomedics MAb, Fab´ location and extent of disease staging Phase III technetium-99m- Morris Plains, NJ fragment of lung cancer arcitumomab (lung) CEAVac™ Titan Pharmaceuticals vaccine colorectal cancer Phase III anti-idiotype S. San Francisco, CA antibody vaccine CEP-701 Tap Holdings prostate cancer Phase I/II Deerfield, IL Cereport™ Alkermes recurrent malignant brain tumor Phase II/III (RMP-7) Cambridge, MA and carboplatin cetuximab ImClone Systems MAb epidermal growth factor receptor Phase II (C225, anti-EGFR Somerville, NJ positive cancers chimeric MAb) chimeric bone Chimeric Therapies cellular leukemia, mismatched Phase I/III marrow cell graft Laguna Niguel, CA therapy bone marrow transplantation (see also blood) chimeric MAb National Cancer Institute MAb melanoma, neuroblastoma Phase II 14.18 Bethesda, MD N C I T R I A L CM 101 CarboMed polysaccharide pancreatic cancer Phase II Brentwood, TN (see also neurologic) CMA-676 Wyeth-Ayerst Laboratories MAb relapsed acute myelogenous application Philadelphia, PA leukemia submitted colon cancer Immune Response vaccine colon cancer Phase I cell line Carlsbad, CA vaccine Sidney Kimmel Cancer Center San Diego, CA Cotara™ Techniclone MAb malignant glioma Phase II Tustin, CA (brain cancer), solid tumors CP-358,774 OSI Pharmaceuticals cellular cancer Phase II Uniondale, NY therapy Pfizer New York, NY CP-609,754 OSI Pharmaceuticals cancer Phase I Uniondale, NY CpG 7909 Coley Pharmaceutical immune-based breast, prostate cancers, Phase I/II Wellesley, MA therapy non-Hodgkin’s lymphoma (see also infectious diseases, respiratory) dendritic/cancer Genzyme Molecular vaccine breast cancer Phase I cell fusion Oncology Cambridge, MA E1A lipid complex Targeted