The Therapeutic Proteins Outlook To 2007: An analysis of leading products and late-stage pipeline developments

TABLE OF CONTENTS

Executive Summary 10

• Overview of the global therapeutic proteins market 10
• Erythropoietins 11
• Interferons 11
• Insulins 12
• Monoclonal antibodies 13
• Blood factors 14
• Colony stimulating factors 15
• Growth hormones 15
• Interleukins 16
• Growth factors 17
• Therapeutic vaccines 17
• Other therapeutic proteins 18

Chapter 1 Overview of the global therapeutic proteins market 22

• Summary 22
• Introduction 23
• Protein classification 23
• Segmentation of the global therapeutic protein market 25
• Major influencers of therapeutic protein market growth 27
• Drug delivery challenges 28
• Injectable systems 28
• Pulmonary delivery 29
• Transdermal technologies 32
• Oral delivery 32
• Manufacturing capacity shortfall 34
• Why is there a capacity shortfall? 34
• Overcoming manufacturing issues 36
• Biogeneric competition 37
• Will gene therapy supercede therapeutic proteins? 39

Chapter 2 Erythropoietins 44

• Summary 44
• Class overview 44
• Mechanism of action 46
• Global sales 46
• Analysis of leading products 47
• Procrit/Eprex (epoetin alpha) 47
• Epogen (epoetin alpha) and Aranesp (darbepoetin alpha) 50
• NeoRecormon/Epogin (epoetin beta) 52
• Late stage R&D activity 53
• Hemolink (hemoglobin raffimer) 54

Chapter 3 Interferons 56

• Summary 56
• Class overview 57
• Mechanism of action 60
• Global sales 60
• Analysis of leading products 62
• Intron family 62
• Intron A (interferon alpha-2b) 63
• PEG Intron (peg interferon alpha-2b) 63
• Rebetol (ribavirin) 64
• Rebetron (interferon alpha-2b + ribavirin) 65
• Roferon-A (interferon alpha-2a) and Pegasys (pegylated interferon alpha-2a) 65
• Avonex (interferon beta-1a) 68
• Rebif (interferon beta) 69
• Late stage R&D activity 70

Chapter 4 Insulins 74

• Summary 74
• Class overview 75
• Mechanism of action 76
• Global sales 77
• Analysis of leading products 78
• Novolin (insulin) 78
• Humulin (insulin) 81
• Humalog (insulin lispro) 82
• Lantus (glargine insulin) 83
• Late stage R&D activity 84
• NN304 (insulin Detemir) 85
• AERx iDMS 86
• Exubera (inhaled insulin) 89

Chapter 5 Monoclonal antibodies 94

• Summary 94
• Class overview 94
• Mechanism of action 99
• Global sales 99
• Analysis of leading products 101
• Mabthera/Rituxan (rituxumab) 101
• Remicade (infliximab) 102
• Herceptin (trastuzumab) 104
• Humira (adalimumab) 106
• Late stage R&D activity 107
• Xolair (omalizumab) 107
• Bexxar (tositumomab) 109
• Raptiva (efalizumab) 111
• Erbitux/IMC-C225 (cetuximab) 113

Chapter 6 Blood factors 118

• Summary 118
• Class overview 118
• Mechanism of action 121
• Global sales 122
• Analysis of leading products 124
• Activase/TNKase (alteplase/tenecteplase) 124
• NovoSeven (rh factor VIIa) 126
• Late stage R&D activity 128

Chapter 7 Colony stimulating factors 132

• Summary 132
• Class overview 132
• Mechanism of action 133
• Global sales 134
• Analysis of leading products 136
• Neupogen (filgrastim) 136
• Neulasta (pegfilgrastim) 136
• Late stage R&D activity 138
• Chapter 8 Growth hormones 140
• Summary 140
• Class overview 140
• Mechanism of action 141
• Global sales 142
• Analysis of leading products 143
• Genotropin (somatropin) 143
• Nutropin/Protropin (somatropin/somatrem) 144
• Norditropin/Norditropin SimpleXx (r-Somatropin) 146
• Saizen (somatropin) 147
• Late stage R&D activity 147
• Serostim (somatropin) 148

Chapter 9 Interleukins 150

• Summary 150
• Class overview 150
• Mechanism of action 151
• Global sales 151
• Analysis of leading products 152
• Proleukin (interleukin-2) 152
• Late stage R&D activity 153

Chapter 10 Growth factors 156

• Summary 156
• Class overview 156
• Mechanism of action 158
• Global sales 159
• Analysis of leading products 160
• Regranex (beclapermin) 160
• Fiblast (trafermin) 160
• Late stage R&D activity 161
• Stemgen (ancetism) 162
• Keratinocyte growth factor 163

Chapter 11 Therapeutic vaccines 166

• Summary 166
• Class overview 166
• Mechanism of action 170
• Global sales 170
• Analysis of leading products 171
• Melacine (theraccine) 171
• M-Vax 172
• OncoVax 172
• Late stage R&D activity 173
• Cancer 173
• HIV 174
• Barriers to HIV vaccine development 176

Chapter 12 Other therapeutic proteins 182

• Summary 182
• Class overview 182
• Global sales 184
• Analysis of leading products 186
• Enbrel (etanercept) 186
• Cerezyme (imiglucerase) 188
• Xigris (drotrecogin alpha) 190
• Late stage R&D activity 193
• Index 196

List of Tables

• Table 1.1: Segmentation and growth of the global therapeutic proteins market by class, 2001-0226
• Table 2.2: Marketed and late stage development erythropoietins 45
• Table 2.3: Erythropoietin sales, 2001-02 46
• Table 2.4: Sales and forecast sales of Amgen's Epogen and Aranesp, 2000-07 51
• Table 3.5: Marketed and late stage development alpha interferons 58
• Table 3.6: Marketed and late stage development beta interferons 59
• Table 3.7: Marketed and late stage development gamma interferons 59
• Table 3.8: Major interferon sales, 2001-02 61
• Table 4.9: Marketed and late stage development insulins 76
• Table 4.10: Insulin sales, 2001-02 78
• Table 5.11: Marketed and late stage development monoclonal antibodies 96
• Table 5.12: Marketed and late stage development monoclonal antibodies (cont'd) 97
• Table 5.13: Marketed and late stage development monoclonal antibodies (cont'd) 98
• Table 5.14: Major monoclonal antibody sales, 2001-02 100
• Table 6.15: Marketed and late stage development plasminogen activators 120
• Table 6.16: Marketed and late stage development blood clotting factors 121
• Table 6.17: Major blood factor sales, 2001-02 123
• Table 7.18: Marketed and late stage development colony stimulating factors 133
• Table 7.19: Major colony stimulating factor sales, 2001-02 135
• Table 8.20: Marketed and late stage development growth hormones 141
• Table 8.21: Growth hormone sales, 2001-02 143
• Table 9.22: Marketed and late stage development interleukins 151
• Table 9.23: Interleukin sales, 2001-02 152
• Table 10.24: Marketed and late stage development growth factors 157
• Table 10.25: Growth factor classes and mechanism of action 158
• Table 10.26: Major growth factor sales, 2001-02 159
• Table 11.27: Marketed and late stage development therapeutic vaccines (cancer) 168
• Table 11.28: Marketed and late stage development therapeutic vaccines (HIV and 'others') 169
• Table 11.29: Major therapeutic vaccine sales, 2001-02 171
• Table 12.30: Marketed and late stage development of 'other' therapeutic proteins 183
• Table 12.31: Sales of major 'other' therapeutic proteins, 2001-02 185

List of Figures

• Figure 1.1: Segmentation of the global therapeutic proteins market by class, 2001-02 26
• Figure 1.2: Timeline of impact: major influencers of therapeutic protein market growth, 2002-1028