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New Cancer Therapeutics: An analysis of current and emerging markets Joseph F. Dooley, Ph.D., FACB Table of Contents In 2001, for the fourth year in a row, the Centers for Disease Control reported a decline in the death rate from cancer, with the most notable decreases in the death rates for breast cancer, prostate cancer, lung cancer, colon cancer and leukemia. This is due in no small part to improved treatments, including more effective prescription drugs. While the death rate from cancer is declining, the number of actual deaths is increasing because of an increasing population and longer life expectancy. The new management report New Cancer Therapeutics: An analysis of current and emerging markets provides detailed analyses of current drugs and developing technologies to predict future market dynamics. The report also assesses the ability of the pharmaceutical sector to meet the significant unmet need that exists in oncology. The expert analysis of trends and forecasts in this report will help you to identify the areas from which you may the yield greatest returns on your R&D investments - saving you time and money. Report Summary Dr. Dooley founded Biotechnology Associates in 1995, which has since become one of the most respected consulting firms in the US, specializing in medical diagnostics and the biotechnology industry. Previously, he established Biomedical Associates in 1981 as a consulting company in the management of clinical laboratories and diagnostic laboratory science. Dr. Dooley is a nationally recognised consultant on medical technology devices. He has over 25 years of experience as Director and CEO of several large national and regional clinical laboratories. Dr. Dooley holds a doctorate in biochemistry and is board certified in clinical laboratory science. He is a Fellow of the American Academy of Clinical Biochemistry.Earlier in his career, Dr. Dooley was a senior research scientist at DuPont Central Research Station, Senior Manager at Pfizer and Director at Dianon Laboratories, a leading cancer diagnostic testing laboratory. Table of Contents New Cancer Therapeutics: An analysis of current and emerging markets Executive Summary 12 Introduction 12 Goals and objectives 14 Study scope and format 15 Methodology 15 Information sources 16 Summary of major findings 16 Chapter 1 Introduction 22 Overview 22 Cancer drugs in development 22 Research focus 24 Increasing survival rates 25 Chapter 2 Market Overview 28 Introduction 28 Cancer therapeutics in the pharmaceutical and biotech industry 28 The role of biotechnology 29 The promise of gene therapy 29 Case study: Antisoma’s Theragyn 30 Case study: ImClone Systems’ Erbitux 31 Genomics 32 Growth potential 35 Business analysis of the cancer market 35 Demographics 38 A global market 39 Markets for cancer therapies 41 Geographical markets 41 The US 43 Europe 44 Japan 45 New product trends 45 Chemotherapy 45 Taxanes 46 Paclitaxel 47 Docetaxel 48 Research into taxanes 48 Cytotoxics 48 Alkylating agents 49 Cisplatin 49 Carboplatin 50 Nitrosureas 51 Antimetabolites 51 Methotrexate 51 Gemcitabine 52 Antitumor antibiotics 53 Doxorubicin 53 Mitotic inhibitors 54 Vinblastine 54 Other cytotoxics 55 Corticosteroid hormones 55 Sex hormones 55 Immunotherapy drugs 55 Chemosensitizers 56 Chemoprotectants 56 Liposomes 57 Drugs for chemotherapy and cancer-related conditions 57 Hormone therapy 58 Photodynamic therapy and photosensitizers 59 Gene therapy 60 Tumor-suppressor gene therapy 61 Immunomodulatory gene therapy 62 Suicide gene therapy 63 Radiation therapy 63 Farnesyl transferase inhibitors (FTIs) 66 Genetic screening 67 Biological therapies 67 Interferons (IFNs) 69 Interleukins (ILs) 70 Tumor necrosis factor (TNF) 70 Colony-stimulating factors (CSFs) 71 Monoclonal antibodies (MAbs) 72 Cancer vaccines 73 Adjuvants 77 Angiogenesis inhibitors 78 Hypothermia 80 Transplants 81 Bone marrow transplants 81 Stem cell transplants 82 Chapter 3 Analysis of Cancer Epidemiology and Causes 84 Introduction 84 US statistics 84 Global statistics 88 New cancer cases and deaths by cancer type 89 New cancer cases and deaths by region 90 WHO death rates by country 93 Causes of cancer 94 Carcinogens 94 Risk factors 96 Smoking 96 Diet 97 Radiation 98 Occupational risks 99 Medicine and infection 101 Environmental pollution 102 Reproductive factors 103 Socioeconomic factors 103 Cancer costs 104 Chapter 4 Analysis of Cancer Diagnoses and Therapies 106 Introduction 106 Bladder cancer 106 Overview 106 Diagnosis and staging 108 Treatment options 109 Surgery 109 Chemotherapy 109 Radiation therapy 111 Immunotherapy 111 Photodynamic therapy 111 Drugs in development 112 Brain cancer 113 Overview 113 Epidemiology 114 Treatment options 115 Current therapeutics 115 Unmet needs 115 Cotara (131I chTNT 1/B) 116 RSR13 (efaproxiral sodium) 117 Xcytrin (motexafin gadolinium) 118 Breast cancer 119 Overview 119 Epidemiology 120 Treatment options 121 Current therapeutics 122 Chemotherapies 124 Advances in chemotherapy 125 Chemotherapy before surgery 127 Analysis of selected cytotoxics 128 Gemzar (gemcitabine) 128 Doxil (liposomal doxorubicin) 129 Tesmilifene (DPPE) 131 Alternatives to cytotoxic drugs 132 SERMs (Selective Estrogen-Receptor Modulators) 133 Aromatase inhibitors 134 Biologic response modifiers 139 Other hormonal therapies 142 Vaccines 147 Theratope (sTn-KLH) 147 Antisense therapy 148 Genasense (augmerosen/G3139) 148 Selected innovative therapies 150 Almita (pemetrexed disodium/LY231514) 150 Avastin (bevacizumab/anti-VEGF) 150 Arcitumomab/CEA-SCAN 153 Targretin (bexarotene) 154 Onconase (ranpirnase) 156 Apomine (SR-45023A/ farnesoid X receptor agonist) 157 Tarceva (erlotinib/OSI-774; formerly CP-358,774) 158 SGN-15 159 ET-743 161 Cervical cancer 163 Overview 163 Treatment options 165 Colorectal cancer 166 Overview 166 Epidemiology 167 Treatment options 168 Current therapeutics 168 Unmet needs 169 Advances in the treatment of colorectal cancer 169 Orathecin (rubitecan) 169 Avastin (bevacizumab) 170 Avicine 171 CeaVac 172 Gastrimmune 173 Eflornithine (DFMO) 174 NeuTrexin (trimetrexate glucuronate) 175 Leukemia 176 Overview 176 Epidemiology 176 Treatment options 177 Current therapeutics 178 Unmet needs 178 Products in development 179 Genasense (augmerosen) 179 Zamyl 180 PEG-Intron A 181 Ceplene (histamine dihydrochloride) 182 Lung cancer 183 Epidemiology 184 Treatment options 185 NSCLC 185 SCLC 185 Malignant mesothelioma 186 Current therapeutics 186 Unmet needs 186 Products in development 188 Aptosyn (exisulind) 188 BMS-184476 189 Hycamtin (topotecan) 190 DX 8951f (exatecan) 191 Tirazone (tirapazamine) 191 Calsed (amrubicin) 192 Navelbine (vinorelbine) 193 ISIS 3521 193 Onconase (ranpirnase) 194 Avastin (bevacizumab) 195 Iressa (gefitinib) 195 Neovastat (AE-941) 196 Tarceva (erlotinib) 197 BEC2 (mitumomab) 198 SRL 172 (mycobacterium vaccae) 199 Alimta (pemetrexed disodium) 200 Targretin (bexarotene) 200 Ovarian cancer 201 Overview 201 Epidemiology 202 Treatment options 203 Current therapeutics 203 Unmet needs 203 Gemzar (gemcitabine) 204 Osidem (IDM-1) 205 Actimmune 206 Pentumomab (formerly Theragyn) 207 Prostate cancer 209 Overview 209 Epidemiology 209 Treatment options 210 Current therapeutics 211 Unmet needs 211 Chapter 5 Corporate Snapshots 214 Introduction 214 Amgen 214 AstraZeneca 216 Aventis 218 Bristol-Myers Squibb 219 Johnson & Johnson 221 Novartis 223 GlaxoSmithKline 225 Pharmacia 226 Roche 229 Schering-Plough 231 Eli Lilly 232 Biotechnology companies 233 Genentech 234 ImClone 236 OSI Pharmaceuticals 237 ISIS Pharmaceuticals 238 Genta 239 Chapter 6 Appendix 242 Data tables 242 Online References for Cancer 249 American Cancer Society 249 Cancer Care 249 Cancer Information Network 249 CancerLinks 250 CancerLinksUSA 250 CancerNet 250 Cancer Survivors’ Network 250 Cancer Trials 250 Memorial Sloan Kettering Cancer Center 251 M. D. Anderson Cancer Center, University of Texas 251 National Cancer Institute 251 OncoLink of the University of Pennsylvania 251 Women’s Cancer Network 251 InteliHealth 252 Mayo Clinic Health Oasis 252 Pharmaceutical Research and Manufacturers of America (PhRMA) 252 Print sources 252 List of Figures Figure 2.1: Cancer therapeutics markets by region, 2001 42 Figure 2.2: Growth in the US market for cancer therapeutics, 1998–2006 43 Figure 2.3: Growth in the European market for cancer therapeutics, 1998–2006 44 Figure 2.4: Growth in the Japanese market for cancer therapeutics, 1998–2006 45 Figure 2.5: Innovations to increase the effectiveness of radiation therapy 65 Figure 3.6: Breakdown of annual costs of cancer in the US 104 List of Tables Table 1.1: Breakdown of medicines in development for cancer, 2001 23 Table 2.2: Breakdown of new biotech cancer therapies in R&D, 2002 31 Table 2.3: Opportunities for molecular-targeting therapeutics for cancer 33 Table 2.4: Leading US biotechnology companies by market capitalization 34 Table 2.5: Breakdown of the US cytostatic market by company share 37 Table 2.6: Developmental cancer vaccines 76 Table 3.7: Estimates of new cancer cases and deaths in the US by sex for all cancer sites*, 2001 85 Table 3.8: Estimates of new cancer cases and deaths in the US by sex for all cancer sites*, 2001 (cont.) 86 Table 3.9: Estimates for the leading sites of new cancer cases and deaths in the US by sex, 200187 Table 3.10: Estimated worldwide number of new cancer cases and deaths by type of cancer (in thousands)* 89 Table 3.11: Estimated worldwide number of new cancer cases and deaths by type of cancer (in thousands)* continued 90 Table 3.12: Estimated number of new cancer cases and deaths by region* 90 Table 3.13: Estimated number of new cancer cases and deaths by region (in thousands)* (cont.) 91 Table 3.14: Cancer death rates per 100,000 population (and rank) for all cancer sites by country, 1992–95 93 Table 3.15: Genes and cancer risk 95 Table 3.16: Carcinogens in the workplace 100 Table 4.17: Drugs used in bladder cancer therapy 111 Table 4.18: Drugs in development for bladder cancer 112 Table 4.19: Brain cancer patient statistics, 2002 114 Table 4.20: Breast cancer patient statistics 2002 120 Table 4.21: Analysis of breast cancer pipeline by company, 2001 123 Table 4.22: Classes of chemotherapy drugs used to treat breast cancer 124 Table 4.23: Classes of drugs used to treat breast cancer 133 Table 4.24: Herceptin: global sales 2000–05 142 Table 4.25: AstraZeneca’s Nolvadex: global sales, 2002–05 144 Table 4.26: Selected medicines in development for cervical cancer 166 Table 4.27: Colorectal cancer patient statistics 2002 167 Table 4.28: Leukemia patient statistics, 2002 177 Table 4.29: Lung cancer patient statistics, 2002 184 Table 4.30: Late-stage pipeline compounds for lung cancer 188 Table 4.31: Ovarian cancer patient statistics, 2002 202 Table 4.32: Late-stage pipeline compounds for ovarian cancer, 2002 204 Table 4.33: Prostate cancer patient statistics, 2002 210 Table 5.34: Amgen’s (Immunex’s) marketed cancer portfolio 215 Table 5.35: AstraZeneca’s marketed cancer portfolio 216 Table 5.36: Aventis’ marketed cancer portfolio 218 Table 5.37: BMS’ marketed cancer portfolio 219 Table 5.38: J&J’s marketed cancer portfolio 221 Table 5.39: Novartis’ marketed cancer portfolio 223 Table 5.40: GSK’s marketed cancer portfolio 225 Table 5.41: Pharmacia’s marketed cancer portfolio 227 Table 5.42: Roche’s marketed cancer portfolio 229 Table 5.43: Schering-Plough’s marketed cancer portfolio 231 Table 5.44: Lilly’s marketed cancer portfolio 232 Table 5.45: Genentech’s marketed cancer products 235 Table 5.46: Genentech’s pipeline cancer products 235 Table 5.47: ImClone Systems’ pipeline cancer products 236 Table 5.48: OSI Pharmaceuticals’ pipeline cancer products 237 Table 5.49: ISIS Pharmaceuticals’ pipeline cancer products 238 Table 5.50: Genta’s pipeline cancer product 239 Table 6.51: Drug approvals for cancer indications alphabetical listing 242 Table 6.52: Drug approvals for cancer indications alphabetical listing 243 Table 6.53: Drug approvals for cancer indications alphabetical listing 244 Table 6.54: Drug approvals for cancer indications alphabetical listing 245 Table 6.55: Drug approvals for cancer indications alphabetical listing 246 Table 6.56: Drug approvals for cancer indications alphabetical listing 247 Table 6.57: Drug approvals for cancer indications alphabetical listing 248 Table 6.58: Drug approvals for cancer indications alphabetical listing 249