Table of Contents

TABLE OF CONTENTS
About the PharmaVitae team 3
Scope of the report 4
CHAPTER 1 EXECUTIVE SUMMARY 5
Key findings 5
Total market outlook 5
Monoclonal antibody market outlook 6
Introduction to the PharmaVitae universe 7
The prescription pharmaceutical market to 2012 9
Prescription pharmaceutical market performance, 2006–12 9
Balance of launches and expiries in the prescription pharmaceutical market, 2006–12 10
The majority of expiry-driven sales occurs between 2011 and 2012 11
Forecast sales performance by molecule type 14
Prescription pharmaceutical sales by molecule type, 2006–12 18
Change in annual sales by molecule type 20
Sales growth rate by molecule type, 2006–12 21
The lack of a biosimilar/generic protein product threat for mAbs 24
Monoclonal antibodies are the most attractive product segment in the prescription pharmaceutical market out to 2012 47
mAb market performance, 2006–12 49
mAb market growth 49
The recurring mAb market theme: dominance of ‘the big 5’ 61
‘Big 5’ revenue preeminence to 2012 63
‘Big 5’ contribute majority of sales growth to 2012 63
‘Big 5’ command highest revenues per product in segment 64
Are mAbs always commercially more attractive than small molecules? 65
Factors determining evolution of a mAb market dominated by ‘big 5’ 67
CHAPTER 2 MAB TECHNOLOGY OVERVIEW 96
Key findings 96
Introduction 97
The immune system 97
Antibody structure 97
Hybridoma technique – the production of mAbs 99
Targets 100
Mode of action 103
Evolution of mAbs 105
Murine 110
Chimeric and humanized antibodies 111
Fully human 113
Fragments 113
Conjugated 117
Naked mAbs still dominate 120
Systematic naming of monoclonal antibodies 121
The mAb timeline – technology evolution 122
Manufacturing 128
CHAPTER 3 MARKET ANALYSIS 132
Key findings 132
Introduction 133
mAb market: historical performance, 2003–06 133
mAb market: forecast performance, 2006–12 136
Historical product analysis, 2003–06 141
Forecast product analysis, 2006–12 145
Growth drivers 151
Growth resistors 158
Historical company analysis, 2003–06 160
Forecast company analysis, 2006–12 165
Growth drivers 169
Historical therapy area analysis, 2003–06 175
Forecast therapy area analysis, 2006–12 177
Growth drivers 179
Historical technology analysis, 2003–06 183
Humanized 184
Chimeric 184
Human 184
Others 185
Forecast technology analysis, 2006–12 185
Growth drivers 187
Historical target analysis, 2003–06 190
Forecast target analysis, 2006–12 194
Growth drivers 197
CHAPTER 4 PIPELINE ANALYSIS 201
Key findings 201
Introduction 202
mAb pipeline overview 203
Company pipeline analysis 211
Technology pipeline analysis 221
Therapy area pipeline analysis 228
Target pipeline analysis 233
CHAPTER 5 PRODUCT OVERVIEW 251
Key findings 251
Oncology 252
Avastin 252
Rituxan/MabThera 256
Herceptin 259
Erbitux 263
Vectibix 267
Pertuzumab 270
Ticilimumab 272
Ipilimumab 274
Humax CD20 277
Lumiliximab 280
Rencarex 283
Mylotarg 286
Campath/MAB Campath 288
Zevalin 290
Bexxar 293
Zalutumumab 295
Zanolimumab 297
Proxinium/Vicinium 299
Catumaxomab 301
AIID 303
Humira 303
Remicade 307
Cimzia 311
Rituxan/MabThera RA 314
Actemra 318
Golimumab 321
Raptiva 324
CNTO-1275 326
Mepolizumab 328
Simulect 330
Lymphocide 332
Zenapax 334
Nuvion 336
Leukotac 338
CNS 340
Tysabri 340
Cardiovascular 344
ReoPro 344
Respiratory 346
Xolair 346
Ophthalmology 349
Lucentis 349
Hematology 352
Soliris 352
AMG-531 354
Women’s health 356
Denosumab 356
Infectious disease 359
Numax 359
Mycograb 362
Aurograb 364
Synagis 366
CHAPTER 6 APPENDIX 368
References 368
Datamonitor reports 368


TABLE OF TABLES
Table 1: PharmaVitae company coverage by peer set 7
Table 2: Molecule type definitions 15
Table 3: General characteristics of small molecule drugs vs. biologics 17
Table 4: Forecast sales by molecule type ($m), 2006–12 18
Table 5: Top 25 sales growth resistors ($m), 2011–12 23
Table 6: Average revenues, 2006 35
Table 7: Average operating cost ratios and operating profit margin for small molecule, therapeutic protein and mAb specialists (%), 2002–06 37
Table 8: Target family classification 43
Table 9: mAb ‘big 5’ in 2003, 2006 and 2012 61
Table 10: Overview of a selection of marketed mAbs: technology type and immunogenicity 107
Table 11: Infix nomenclature for mAbs 121
Table 12: Manufacturing cell lines for marketed mAbs 130
Table 13: Forecast product sales ($m), 2006–12 145
Table 14: Forecast mAb sales by company ($m), 2006–12 165
Table 15: Forecast sales by therapy area ($m), 2006–12 177
Table 16: Forecast sales by mAb technology type ($m), 2006–12 185
Table 17: Forecast sales by target ($m), 2006–12 194
Table 18: mAb pipeline Phase I–pre-registration overview 203
Table 19: Count of marketed mAbs 211
Table 20: Count of Phase III mAb players 214
Table 21: Count of companies with more than one Phase I–II pipeline candidates 217
Table 22: mAb count split by technology type 222
Table 23: Count of mAb candidates by therapy area 229
Table 24: Detailed product/target analysis 233
Table 25: Novel late-stage targets 236
Table 26: Novel early-stage candidates 240
Table 27: Companies with multiple novel early-stage targets 244
Table 28: TNF alpha-targeting mAbs 247
Table 29: CD20-targeting mAbs 249
Table 30: Avastin: overview 252
Table 31: Avastin global sales ($m), 2006–12 253
Table 32: Avastin: news flow 253
Table 33: Rituxan/MabThera: overview 256
Table 34: Rituxan/MabThera global sales ($m), 2006–12 256
Table 35: Rituxan/MabThera: news flow 257
Table 36: Herceptin: overview 259
Table 37: Herceptin global sales ($m), 2006–12 259
Table 38: Herceptin: news flow 260
Table 39: Erbitux: overview 263
Table 40: Erbitux global sales ($m), 2006–12 263
Table 41: Erbitux: news flow 264
Table 42: Vectibix: overview 267
Table 43: Vectibix global sales ($m), 2006–12 267
Table 44: Vectibix: news flow 268
Table 45: Pertuzumab: overview 270
Table 46: Pertuzumab global sales ($m), 2006–12 271
Table 47: Pertuzumab: news flow 271
Table 48: Ticilimumab: overview 272
Table 49: Ticilimumab global sales forecast ($m), 2006–12 272
Table 50: Ticilimumab: news flow 273
Table 51: Ipilimumab: overview 274
Table 52: Ipilimumab global sales ($m), 2006–12 275
Table 53: Ipilimumab: news flow 275
Table 54: Humax CD20: overview 277
Table 55: Humax CD20 global sales ($m), 2006–12 277
Table 56: HuMax CD20: news flow 278
Table 57: Lumiliximab: overview 280
Table 58: Lumiliximab global sales ($m), 2006–12 280
Table 59: Lumiliximab: news flow 281
Table 60: Rencarex: overview 283
Table 61: Rencarex global sales ($m), 2006–12 283
Table 62: Rencarex: news flow 284
Table 63: Mylotarg: overview 286
Table 64: Mylotarg global sales ($m), 2006–12 286
Table 65: Mylotarg: news flow 287
Table 66: MAB Campath: overview 288
Table 67: MAB Campath global sales ($m), 2006–12 288
Table 68: MAB Campath: news flow 289
Table 69: Zevalin: overview 290
Table 70: Zevalin global sales ($m), 2006–12 291
Table 71: Zevalin: news flow 291
Table 72: Bexxar: overview 293
Table 73: Bexxar global sales ($m), 2006–12 293
Table 74: Bexxar: news flow 294
Table 75: Zalutumumab: overview 295
Table 76: Zalutumumab global sales ($m), 2006–12 295
Table 77: Zalutumumab: news flow 296
Table 78: Zanolimumab: overview 297
Table 79: Zanolimumab global sales ($m), 2006–12 297
Table 80: Zanolimumab: news flow 298
Table 81: Proxinium/Vicinium: overview 299
Table 82: Proxinium/Vicinium: news flow 300
Table 83: Catumaxomab: overview 301
Table 84: Catumaxomab: news flow 302
Table 85: Humira: overview 303
Table 86: Humira global sales ($m), 2006–12 303
Table 87: Humira: news flow 304
Table 88: Remicade: overview 307
Table 89: Remicade global sales ($m), 2006–12 307
Table 90: Remicade: news flow 308
Table 91: Product: overview 311
Table 92: Cimzia global sales ($m), 2006–12 311
Table 93: Product: news flow 312
Table 94: Rituxan/MabThera RA: overview 314
Table 95: Rituxan/MabThera global sales ($m), 2006–12 315
Table 96: Rituxan/MabThera RA: news flow 315
Table 97: Actemra: overview 318
Table 98: Actemra global sales ($m), 2006–12 318
Table 99: Actemra: news flow 319
Table 100: Golimumab: overview 321
Table 101: Golimumab global sales ($m), 2006–12 321
Table 102: Golimumab: news flow 322
Table 103: Raptiva: overview 324
Table 104: Raptiva global sales ($m), 2006–12 324
Table 105: Raptiva: news flow 325
Table 106: CNTO-1275: overview 326
Table 107: CNTO-1275 global sales ($m), 2006–12 326
Table 108: CNTO-1275: news flow 327
Table 109: Mepolizumab: overview 328
Table 110: Mepolizumab global sales ($m), 2006–12 328
Table 111: Product: news flow 329
Table 112: Simulect: overview 330
Table 113: Simulect global sales ($m), 2006–12 330
Table 114: Simulect: news flow 331
Table 115: Lymphocide: overview 332
Table 116: Lymphocide global sales ($m), 2006–12 332
Table 117: Lymphocide: news flow 333
Table 118: Zenapax: overview 334
Table 119: Zenapax global sales ($m), 2006–12 334
Table 120: Zenapax: news flow 335
Table 121: Nuvion: overview 336
Table 122: Nuvion global sales ($m), 2006–12 336
Table 123: Nuvion: news flow 337
Table 124: Leukotac: overview 338
Table 125: Leukotac: news flow 339
Table 126: Tysabri: overview 340
Table 127: Tysabri global sales ($m), 2006–12 340
Table 128: Tysabri: news flow 341
Table 129: ReoPro: overview 344
Table 130: ReoPro global sales ($m), 2006–12 344
Table 131: ReoPro: news flow 345
Table 132: Xolair: overview 346
Table 133: Xolair global sales ($m), 2006–12 346
Table 134: Xolair: news flow 347
Table 135: Lucentis: overview 349
Table 136: Lucentis global sales ($m), 2006–12 350
Table 137: Lucentis: news flow 350
Table 138: Soliris: overview 352
Table 139: Soliris global sales ($m), 2006–12 352
Table 140: Soliris: news flow 353
Table 141: AMG-531: overview 354
Table 142: AMG-531 global sales ($m), 2006–12 354
Table 143: AMG-531: news flow 355
Table 144: Denosumab: overview 356
Table 145: Denosumab global sales ($m), 2006–12 356
Table 146: Denosumab: news flow 357
Table 147: Numax: overview 359
Table 148: Numax global sales ($m), 2006–12 359
Table 149: Numax: news flow 360
Table 150: Mycograb: overview 362
Table 151: Mycograb global sales ($m), 2006–12 362
Table 152: Mycograb: news flow 363
Table 153: Aurograb: overview 364
Table 154: Aurograb global sales ($m), 2006–12 364
Table 155: Aurograb: news flow 365
Table 156: Synagis: overview 366
Table 157: Synagis global sales ($m), 2006–12 366
Table 158: Synagis: news flow 367


TABLE OF FIGURES
Figure 1: Pharmaceutical market performance, sales ($m) and year-on-year growth (%), 2006–12 9
Figure 2: Sales growth by launch, core & expiry (ethical sales $m), 2006–12 11
Figure 3: Expiry portfolio, year-on-year change in annual sales ($m), 2006–12 12
Figure 4: Launch, core and expiry portfolio year-on-year change in annual sales ($m), 2006–12 13
Figure 5: Forecast sales by molecule type ($m), 2006–12 19
Figure 6: Change in annual sales ($m) by molecule type, 2006–12 20
Figure 7: Sales compound annual growth rate (CAGR) by molecule type, 2006–12 21
Figure 8: Levels of structural similarity by drug type 26
Figure 9: Average revenues per product ($m), 2006 36
Figure 10: Percentage of oncology and AIID sales by molecule type, 2006 39
Figure 11: Percentage of oncology and AIID sales by molecule type, 2012 40
Figure 12: The role of drug targets in disease treatment 41
Figure 13: Molecule type sales by target family, 2006 44
Figure 14: Total market sales growth (CAGR %) by target family, 2006–12 46
Figure 15: Sales growth drivers and resistors for mAbs, therapeutic proteins and small molecules 48
Figure 16: mAb market outlook, sales ($m) and year-on-year growth (%), 2006–12 49
Figure 17: Product analysis, historical and forecast sales growth ($m), 2006–12 51
Figure 18: Product growth drivers and resistors ($m), 2006–12 52
Figure 19: Company analysis, historical and forecast sales growth ($m), 2006–12 53
Figure 20: Company growth drivers and resistors ($m), 2006–12 54
Figure 21: Therapy analysis, historical and forecast sales growth ($m), 2006–12 55
Figure 22: Therapy area growth drivers and resistors ($m), 2006–12 56
Figure 23: Technology analysis, historical and forecast sales growth ($m), 2006–12 57
Figure 24: Technology growth drivers and resistors ($m), 2006–12 58
Figure 25: Target analysis, historical and forecast sales growth ($m), 2006–12 59
Figure 26: Target growth drivers and resistors ($m), 2006–12 60
Figure 27: The ‘big 5’ mAbs have held over 70% of mAb sales since 2003 and are forecast to retain this market dominance until 2012 62
Figure 28: Total mAb sales ($m) of the ‘big 5’ vs. ‘the rest’ 63
Figure 29: Absolute growth of the ‘big 5’ mAbs vs. ‘the rest’ 64
Figure 30: Average revenues per product in 2006 of the ‘big 5’ mAbs and ‘the rest’ 65
Figure 31: Quartile analysis, average 2006 revenues per product ($m) 66
Figure 32: Dominance of the oncology mAb segment by Avastin, Rituxan and Herceptin 70
Figure 33: Dominance of AIID biologic market by Remicade, Humira and Enbrel 76
Figure 34: The structure of an antibody 98
Figure 35: Types of antibodies 106
Figure 36: Immunogenicity ranges 108
Figure 37: Number of marketed mAb technologies 109
Figure 38: Schematic illustration of antibody fragments 115
Figure 39: Number of marketed full length mAbs versus fragments 116
Figure 40: Number of Phase I–marketed mAb fragments 117
Figure 41: Number of marketed naked and conjugated mAbs 120
Figure 42: mAb timeline – technology shift 123
Figure 43: Ethical sales ($m) and year-on-year growth rate (%), 2003–06 135
Figure 44: Ethical sales ($m) and year-on-year growth rate (%), 2006–12 136
Figure 45: Absolute sales growth rate (ethical sales) ($m), 2003–12 137
Figure 46: mAb CAGRs (%), 2003–12 140
Figure 47: Growth drivers/resistor products of historical revenue performance ($m), 2003–06 141
Figure 48: Product analysis, historical and forecast sales growth ($m), 2003–12 147
Figure 49: mAb count and average mAb sales per mAb, 2003–12 150
Figure 50: Product growth drivers and resistors ($m), 2006–12 151
Figure 51: Key growth driver companies by historical revenue performance ($m), 2003–06 160
Figure 52: Company analysis, historical and forecast sales growth ($m), 2003–12 166
Figure 53: Company growth drivers and resistors ($m), 2006–12 169
Figure 54: Growth drivers/resistor therapy areas of historical revenue performance ($m), 2003–06 175
Figure 55: Therapy analysis, historical and forecast sales growth ($m), 2003–12 178
Figure 56: Therapy area growth drivers and resistors ($m), 2006–12 179
Figure 57: Growth drivers/resistor technologies of historical revenue performance ($m), 2003–06 183
Figure 58: Technology analysis, historical and forecast sales growth ($m), 2003–12 186
Figure 59: Technology growth drivers and resistors ($m), 2006–12 187
Figure 60: Growth drivers/resistor targets of historical revenue performance ($m), 2003–06 190
Figure 61: Target analysis, historical and forecast sales growth ($m), 2003–12 195
Figure 62: Target growth drivers and resistors ($m), 2006–12 196
Figure 63: Count of marketed mAb players 212
Figure 64: Count of Phase III pipeline mAb players 215
Figure 65: Count of companies with more than one Phase I–II pipeline candidates 218
Figure 66: Emerging mAb players 220
Figure 67: Phase I–III pipeline count split by technology 223
Figure 68: The stepwise evolution of naked mAb technology 224
Figure 69: Overview of pipeline technology type Phase I–pre-reg 225
Figure 70: Emerging mAb technologies (% mAb candidates) 227
Figure 71: Phase I–pre-reg mAb count split by therapy area 230
Figure 72: Percentage contribution from mAb candidates, 2006 232
Figure 73: Phase III and pre-registration target count 234
Figure 74: Count of targets with more than one Phase I–II pipeline candidates 238
Figure 75: Count of the most popular targets in early-stage development 243