CHAPTER ONE: INTRODUCTION.1 STUDY GOALS AND OBJECTIVES... 1 REASONS FOR DOING THIS STUDY... 1 INTENDED AUDIENCE... 1 SCOPE OF REPORT... 2 METHODOLOGY... 2 INFORMATION SOURCES... 3 AUTHOR S CREDENTIALS... 3 RELATED BCC REPORTS... 3 BCC ONLINE SERVICES... 3 DISCLAIMER... 4 CHAPTER TWO: SUMMARY... 5 SUMMARY... 5 SUMMARY TABLE THE WORLDWIDE MARKET FOR THERAPEUTIC VACCINES BY INDICATION, THROUGH 2014 ($ MILLIONS)... 6 SUMMARY FIGURE THE WORLDWIDE MARKET FOR THERAPEUTIC VACCINES BY INDICATION, 2010-2014... 6 CHAPTER THREE: OVERVIEW... 7 DEFINITION OF A THERAPEUTIC VACCINE... 7 IMMUNE SYSTEM OVERVIEW: CAST OF CHARACTERS... 7 B-CELLS, T-CELLS AND ANTIGEN-PRESENTING CELLS... 7 B-Cells... 8 T-Cells... 8 Antigen-Presenting Cells... 8 CELLULAR VERSUS HUMORAL IMMUNITY... 8 INNOVATIVE APPROACHES TO VACCINE TECHNOLOGY... 9 DNA VACCINES... 9 CARBOHYDRATE VACCINES... 9 THE ROLE OF ADJUVANTS... 10 ATTRACTIVE FEATURES OF THERAPEUTIC VACCINES VERSUS OTHER CLASSES OF THERAPIES... 11 TABLE 1 FEATURES OF THERAPEUTIC VACCINES VERSUS OTHER DRUG CLASSES... 11 THERAPEUTIC VACCINES APPROVED FOR CLINICAL USE OR IN CLINICAL TRIALS... 11 TABLE 2 THERAPEUTIC VACCINES IN CLINICAL TRIALS, ORDERED BY PHASE... 11 TABLE 2 (CONTINUED)... 12 TABLE 2 (CONTINUED)... 13 TABLE 2 (CONTINUED)... 14 TABLE 2 (CONTINUED)... 15 TABLE 3 NUMBER OF THERAPEUTIC VACCINES IN CLINICAL TRIALS, BY PHASE... 15
FIGURE 1 VACCINES IN CLINICAL TRIALS BY INDICATION, 2010 (%)... 16 TABLE 4 VACCINES IN CLINICAL TRIALS BY TECHNOLOGY... 16 TABLE 5 COMPANIES WITH THERAPEUTIC VACCINES IN CLINICAL TRIALS... 17 CHAPTER FOUR: TECHNOLOGY OVERVIEW... 18 TYPES OF THERAPEUTIC VACCINES... 18 TABLE 6 COMPARISON OF AUTOLOGOUS VERSUS ALLOGENEIC VACCINES... 18 TABLE 7 NUMBER OF ALLOGENEIC AND AUTOLOGOUS THERAPEUTIC VACCINES IN DEVELOPMENT BY PHASE... 19 CHAPTER FIVE: PATENT EVALUATION... 20 PATENT LENGTHS AND MARKET EXCLUSIVITY... 20 TABLE 8 PATENT EXPIRATION DATES FOR THERAPEUTIC VACCINES IN LATE STAGES OF DEVELOPMENT... 21 CHAPTER SIX: PRODUCTS... 22 ADDICTION VACCINES... 22 TABLE 9 ADDICTION VACCINES IN DEVELOPMENT BY PHASE... 23 TABLE 10 THE WORLDWIDE MARKET FOR ADDICTION VACCINES, THROUGH 2014 ($ MILLIONS)... 23 COCAINE ADDICTION VACCINES... 24 The Market for Cocaine Addiction Vaccines... 24 TA-CD... 25 NICOTINE ADDICTION VACCINES... 26 The Market for Nicotine Addiction Vaccines... 27 NicVAX... 28 TABLE 11 NICOTINE ABSTINENCE RATE AT 12 MONTHS IN DIFFERENT STUDIES (%)... 29 NIC002... 29 TA-NIC... 30 AUTOIMMUNE DISEASE VACCINES... 31 TABLE 12 AUTOIMMUNE DISEASE VACCINES IN DEVELOPMENT BY PHASE... 31 DIABETES (TYPE 1)... 31 Diamyd (rhgad65)... 32 Diamyd (rhgad65) (Continued)... 33 BHT-3021... 34 Tovaxin... 35 TNFaKinoid... 35 CANCER VACCINES... 36 CANCER STATISTICS... 37 U.S. Cancer Statistics... 37
TABLE 13 INCIDENCE, MORTALITY, AND SURVIVAL RATES FOR COMMON CANCERS IN THE U.S., 2009... 38 TABLE 14 CANCER PREVALENCE RATES IN THE U.S., 2006 (THOUSANDS)... 39 Current Treatment Methods... 39 Surgery... 39 Radiation Therapy... 40 Pharmaceutical Therapy... 40 CANCER VACCINES: A NEW MODALITY OF CARE... 41 The Primary Therapeutic Role for Cancer Vaccines... 42 The Immune System and Cancer... 43 Antigens: Their Role in Cancer Vaccines... 43 Antigens Used in Cancer Vaccine Development... 44 Carcinoembryonic Antigen... 44 Ganglioside Molecules... 44 Heat Shock Proteins... 45 MART-1... 45 Prostate-Specific Antigen... 45 Sialyl Tn... 46 Tyrosinase... 46 MAGE... 46 NY-ESO-1... 46 MUC1... 46 Vaccine Development: Strategies... 47 Vaccine Development: (Continued)... 48 A Summary of Two Approaches: Low-technology vs. Hightechnology... 49 Vaccine Types... 49 Antigen/Adjuvant Vaccines... 49 Dendritic Cell Vaccines (DCs)... 49 DNA and Viral Vector Vaccines... 49 Idiotype Vaccines... 50 Oncolytic Virus Vaccines... 50 Whole Cell Tumor Vaccines... 50 TABLE 15 TYPES OF VACCINES IN DEVELOPMENT FOR CANCER TREATMENT... 51 The Long Road to Market... 51 The Market for Cancer Vaccines... 52 TABLE 16 ESTIMATED INITIAL U.S. MARKET OPPORTUNITY FOR CANCER VACCINES BY INDICATION... 52 TABLE 17 WORLDWIDE MARKET FOR HUMAN CANCER VACCINES BY TYPE, THROUGH 2014 ($ MILLIONS)... 53
TABLE 18 THE MARKET FOR HUMAN CANCER VACCINES, BY TECHNOLOGY (AUTOLOGOUS VERSUS ALLOGENEIC), WORLDWIDE, THROUGH 2014 ($ MILLIONS)... 53 FIGURE 2 NUMBER OF AUTOLOGOUS VERSUS ALLOGENEIC CANCER VACCINES IN DEVELOPMENT, 2010 (%)... 54 TABLE 19 THE WORLDWIDE MARKET FOR HUMAN CANCER VACCINES, BY INDICATION, THROUGH 2014 ($ MILLIONS)... 54 CANCER VACCINES IN DEVELOPMENT... 55 TABLE 20 CANCER VACCINES IN PHASE II OR LATER TRIALS BY PHASE... 55 TABLE 20 (CONTINUED)... 56 CANCER VACCINES APPROVED FOR USE ON THE WORLDWIDE MARKET... 57 Melacine... 57 Oncophage... 58 Oncophage (Continued)... 59 M-Vax... 60 M-Vax (Continued)... 61 CANCER VACCINES IN DEVELOPMENT... 62 Provenge (APC8015, Sipuleucel-T)... 62 TABLE 21 PROVENGE PHASE III CLINICAL TRIAL RESULTS... 63 Provenge (Continued)... 64 OncoVAX... 65 OncoVAX (Continued)... 66 MyVax... 67 BiovaxId... 68 BiovaxId (Continued)... 69 Multikine... 70 Multikine (Continued)... 71 GSK1572932A... 72 TABLE 22 EXPRESSION OF MAGE-A3 ANTIGEN BY TUMOR TYPE (%)... 73 GSK2132231A... 74 BLP25 Liposome Vaccine (Stimuvax)... 74 BLP25 Liposome (Continued)... 75 BLP25 Liposome (Continued)... 76 TroVax... 77 PR1 Peptide Vaccine... 78 Allovectin-7... 78 Allovectin-7 (Continued)... 79 Belagenpumatucel-L (Lucanix)... 80 GV1001... 80 CB-10-01... 81 MelCancerVac... 81
GRNVAC1... 82 DCVax-Brain... 83 AGS-003... 84 Glionix... 84 CYT004-MelQbG10... 85 CDX-110 (PF-04948568)... 85 GI-4000... 86 TABLE 23 OCCURRENCE OF RAS MUTATIONS IN VARIOUS SOLID TUMORS (%)... 86 HyperAcute-Pancreas... 86 HyperAcute Melanoma... 87 HyperAcute-Lung... 87 PEP223... 88 IMA901... 88 JX-594... 89 Onyvax-P (ONY-P1)... 89 Onyvax-P (ONY-P1) (Continued)... 90 TG4010 (MVA-MUC1-IL2)... 91 TG1042 (Ad-IFNγ)... 92 TG4001/R3484 (MVA-HPV-IL2)... 92 Abagovomab... 93 CV9103... 93 AE37... 94 NeuVax (E75)... 95 ProstVac... 95 INFECTIOUS DISEASE VACCINES... 96 TABLE 24 INFECTIOUS DISEASE VACCINES IN DEVELOPMENT BY PHASE... 96 HIV/AIDS... 97 THE HIV INFECTION PROCESS... 97 HIV TRANSMISSION... 98 CONFUSION REGARDING THE PROPHYLACTIC VERSUS THERAPEUTIC ACTIVITY OF AIDS VACCINES... 98 BARRIERS TO DEVELOPING AND TESTING AIDS VACCINES... 99 Barriers to Developing (Continued)... 100 WHAT HAS BEEN LEARNED... 101 THE MARKET FOR AIDS VACCINES... 102 HIV THERAPEUTIC VACCINES IN DEVELOPMENT... 102 Results of Early Trials of HIV/AIDS Vaccines... 103 AIDSVAX, the Most Advanced HIV Vaccine Candidate but with Mixed Results... 104 The Failure of Merck s V520 Prophylactic and Therapeutic Vaccine... 105
The Remune (AG1661, HIV-1 Immunogen) Saga... 105 The Remune (Continued)... 106 ALVAC-HIV (vcp1521), AIDSVAX Combination... 107 HIV Vaccine 732461... 108 Prophylactic and/or Therapeutic HIV Vaccine... 108 Vacc-4x... 108 DermaVir (LC002)... 109 AGS-004... 109 OTHER INFECTIOUS DISEASE VACCINES (OUTSIDE HIV)... 110 HEPATITIS C... 110 GI-5005... 111 TG4040 (MVA-HCV)... 111 IC41... 112 NEUROLOGICAL DISEASE VACCINES... 112 TABLE 25 NEUROLOGICAL DISEASE VACCINES IN DEVELOPMENT... 112 THE MARKET FOR NEUROLOGICAL DISEASE VACCINES... 113 Alzheimer s Disease Vaccine (AN-1792) (Discontinued)... 113 ACC-001... 114 CAD106... 114 PARKINSON S DISEASE VACCINE... 115 OTHER DISEASE VACCINES... 115 TABLE 26 OTHER DISEASE VACCINES IN DEVELOPMENT... 115 CYT006-AngQb... 115 Angiotensin Therapeutic Vaccine... 116 Angiotensin (Continued)... 117 CHAPTER SEVEN: MAJOR COMPANIES AND MARKET SHARE... 118 MARKET SHARE... 118 TABLE 27 FORECASTED SALES AND MARKET SHARE OF COMPANIES INVOLVED IN THERAPEUTIC VACCINES, 2014 ($ MILLIONS/%)... 118 COMPANY PROFILES... 119 AFFIRIS... 119 ANTIGENICS... 120 ARGOS THERAPEUTICS... 121 BAVARIAN NORDIC... 121 BIOVEST INTERNATIONAL... 122 CELLDEX THERAPEUTICS... 123 CEL-SCI... 123 CELTIC PHARMA... 124 CUREVAC... 124 CYTOS BIOTECHNOLOGY... 125 DENDREON... 126 DIAMYD MEDICAL... 127 ELAN... 127
GENEXINE... 128 GERON... 128 GLAXOSMITHKLINE... 129 GLAXOSMITHKLINE U.S.... 129 GLOBEIMMUNE... 130 KAEL... 131 MERCK KGAA (MERCK SERONO)... 131 NABI BIOPHARMACEUTICALS... 132 NEWLINK GENETICS... 132 NOVARTIS... 133 NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH... 133 NOVARX... 133 ONCOTHYREON... 134 OXFORD BIOMEDICA... 134 PFIZER... 135 TRANSGENE... 136 VACCINOGEN... 137 VACCINOGEN U.S.... 137 VICAL... 137 Vical (Continued)... 138 CHAPTER EIGHT: INTERNATIONAL ASPECTS AND REGULATORY ISSUES... 139 MARKET BY REGION... 139 TABLE 28 GLOBAL FORECAST FOR THERAPEUTIC VACCINES MARKET BY REGION, THROUGH 2014 ($ MILLIONS)... 139 MARKET BY REGION (CONTINUED)... 140 UNITED STATES... 141 The FDA Modernization Act of 1997... 141 Fast-track Status... 141 Special Protocol Assessments... 142 New Surveillance and Safety Requirements... 142 Approvable Letters No More... 143 Medicare... 143 Other Healthcare Changes... 144 EUROPEAN UNION... 144 New Drug Approvals and Innovation... 144 New Drug (Continued)... 145 Drug Reimbursement and Reference Pricing... 146 Relocation of R&D... 147 Regulatory Climate... 147 JAPAN... 148 New Drug Approvals... 148 Regulatory Climate... 148 Relationship between Academia and Industry... 149
CHAPTER NINE: FUTURE DIRECTIONS... 150 THERAPEUTIC VACCINES AS FIRST-LINE THERAPIES... 150 THE ROLE OF BIOMARKERS... 151 VACCINES AND CLINICAL TRIAL DESIGN... 151 COMBINATION THERAPIES... 152