Monoclonal Antibodies Report: 2008 Update - Detailed analysis of the monoclonal antibody segment, encompassing market dynamics, key therapy areas, technology and target types through to 2013, evaluating the strategies companies are using to capitalize on

Monoclonal Antibodies Report: 2008 Update - Detailed analysis of the monoclonal antibody segment, encompassing market dynamics, key therapy areas, technology and target types through to 2013, evaluating the strategies companies are using to capitalize on

Introduction

The report provides a comprehensive financial and strategic analysis of the mAb market, forecasting its commercial evolution out to 2013 and assessing trends by product, company, therapy area, technology and target type. It also provides an insight into the direction of mAb technology evolution and an analysis of pipeline dynamics.

Scope

Comprehensive financial strategic analysis of the mAb market out to 2013 Global sales forecasts to 2013 for marketed and Phase III mAb products Analysis of market trends by product, company, therapy area, technology and target type Analysis of characteristics of key products and insight into direction of mAb technology evolution and pipeline dynamics

Highlights

The overall prescription pharmaceutical market is expected to face a decline in sales over 2011 to 2012 as a result of the 'patent cliff'. The patent cliff will impact the small molecule market, in contrast, the mAb market segment will continue to record robust growth. Over the forecast period monoclonal antibodies are predicted to enjoy double-digit growth while small molecule drugs face declining growth rates. The main barrier to sales growth for small molecules is exposure to material generic competition, which will have no effect on mAbs out to 2013. mAbs currently command a three-fold average revenue per product premium over small molecules. Positive factors supporting this premium include a higher demand due to addressing therapy areas of high unmet need and lower competitive intensity due to accessing novel target space.

Reasons to Purchase

Assess the key products that will drive sales growth in the mAb market to 2013 Understand the challenges and barriers to entry for new players seeking to venture into the mAb market Understand the nature of the generic threat across different molecule types and the insulation of mAb products from biosimilars.

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
Summary of key changes made to mAb market forecast since 2007 report 8
Introduction to the PharmaVitae company universe 10
The prescription pharmaceutical market to 2012 13
Prescription pharmaceutical market performance, 2007-12 13
Balance of launches and expiries in the prescription pharmaceutical market, 2007-12 14
Forecast sales performance by molecule type 15
Small molecules 16
Therapeutic proteins 17
Monoclonal antibodies 17
Vaccines 17
Industry consequences of molecule type 18
Prescription pharmaceutical sales by molecule type, 2007-12 20
Changes in annual sales by molecule type 21
Sales growth rate by molecule type, 2007-13 22
Average revenue analysis 23
Monoclonal antibodies are the most attractive product segment in the prescription pharmaceutical market out to 2012 25
mAb market to 2013 28
mAb market performance, 2007-13 28
Product analysis (size) 29
Product analysis (growth) 31
The two key commercial mAb groups: The 'Big 5' and the 'Emerging 8' 32
The 'Big 5' mAbs 33
The 'Emerging 8' mAbs 35
Commercial dominance of the 'Big 5' and the 'Emerging 8' within the mAb segment 37
Company level sales growth 40
Therapy area level sales growth 42
Technology level sales growth 44
Target level sales growth 45
Scientific and market forces driving mAb success 46
Understanding the forces driving the commercial success of the 'Big 5' monoclonal antibodies 46
Each monoclonal antibody has achieved a first-to-market 'land grab' of a novel target 47
Subsequent horizontal market expansion 47
Ever-rising barriers to entry for competitor products 48
Idealized representation of 'Big 5' evolution 49
Case studies of 'Big 5' mAb commercial evolution 52
Tyrosine kinase domain provide a route to receptor targets 53
Summary - The 'mAb landscape' in 2013 57
How the mAb landscape map was created 57
Key feature 1 of the mAb landscape - the 'Big 5' mAbs 59
Key feature 2 of the mAb landscape - novel targets within the 'Emerging 8' 59
Key feature 3 of the mAb landscape - spanning multiple therapy areas 59
Key feature 4 of the mAb landscape - small molecule incursion 59
CHAPTER 2 MAB TECHNOLOGY OVERVIEW 64
Key findings 64
Introduction 65
The immune system 65
B lymphocytes and antibodies 65
Antibody structure 65
Hybridoma technique - the production of mAbs 67
Monoclonal antibodies as therapeutic agents 67
Targets 68
Target selection - the importance of an accessible epitope 68
Production of mAbs 69
Transgenic mice 69
Phage display 70
Future focus 70
Mode of action 71
mAb-focused oncology 71
The effect of the effector region 72
Blockade 72
mAbs as a delivery vehicle 72
Evolution of mAbs 73
Limitations associated with immunization 73
Murine 78
Chimeric and humanized antibodies 79
Chimeric 79
Humanized 80
Fully human 81
Fragments 81
Conjugated 84
Radiolabeled conjugated mAbs 84
Focus for antibody R&D - oncology immunotoxin drug conjugates 85
Naked mAbs still dominate 87
Systematic naming of monoclonal antibodies 88
The mAb timeline - technology evolution 89
Manufacturing 95
Time to market and manufacturing of monoclonal antibodies 95
Mammalian cell culture - still the most widely-used system 96
CHAPTER 3 MARKET ANALYSIS 99
Key findings 99
Introduction 100
mAb market: historical performance, 2001-07 100
mAb market: forecast performance, 2007-13 103
Product analysis 104
Historical product analysis, 2001-07 105
Historical product growth drivers 108
Remicade (infliximab) 108
Herceptin (trastuzumab) 109
Avastin (bevacizumab) 110
MabThera/Rituxan (rituximab) 110
Humira (adalimumab) 111
Forecast product analysis, 2007-13 112
Forecast product growth drivers 115
Avastin 115
Humira 117
Bapineuzumab 118
Denosumab 119
MabThera/Rituxan 120
Numax 121
Herceptin 122
Golimumab 123
Forecast product growth resistors 124
Remicade 124
Synagis 125
Company analysis 126
Historical company analysis, 2001-07 127
Historical company growth drivers 129
Genentech and Roche 129
Abbott Laboratories 133
Johnson & Johnson 133
Forecast company analysis, 2007-13 134
Forecast company growth drivers 137
Genentech and Roche 137
Abbott 138
Amgen 139
Elan & Wyeth 140
Therapy area analysis 141
Historical therapy area analysis, 2001-07 142
Historical therapy area growth drivers 144
Oncology 144
Immunology & inflammation 145
Forecast therapy area analysis, 2007-13 146
Forecast therapy area growth drivers 147
Oncology 147
Immunology & inflammation 149
Central nervous system 150
Musculoskeletal 150
Technology analysis 151
Historical technology analysis, 2001-07 152
Historical technology growth drivers 154
Humanized mAb 154
Chimeric mAb 154
Human mAb 154
Forecast technology analysis, 2007-13 155
Forecast technology growth drivers 157
Humanized mAb 157
Human mAb 157
Antibody fragment 158
Chimeric mAb 158
Target analysis 159
Historical target analysis, 2001-07 159
Historical target growth drivers 161
TNF alfa 161
VEGF 162
HER2 163
CD20 163
EGFR 163
Forecast target analysis, 2007-13 164
Forecast target growth drivers 166
VEGF 166
TNF alfa 167
Amyloid beta 167
CD20 168
RANKL 168
HER2 169
CHAPTER 4 PIPELINE ANALYSIS 170
Key findings 170
Introduction 171
mAb pipeline overview 172
Company pipeline analysis 178
Early-stage company pipeline analysis 184
Technology pipeline analysis 189
Human content of mAbs, the future focus 194
Therapy area pipeline analysis 195
Target pipeline analysis 198
Target crowding evident with the late-stage mAbs - with lifecycle management strategies being employed 199
Novel target early-stage candidates 202
Will further launches add to target crowding? 209
CD20 210
TNF alfa 211
HER2 and VEGF 212
CHAPTER 5 PRODUCT OVERVIEW 213
Key findings 213
Oncology 214
Avastin 214
Overview 214
Sales forecast 215
Rituxan/MabThera 216
Overview 216
Sales forecast 216
Herceptin 218
Overview 218
Sales forecast 218
Erbitux 220
Overview 220
Sales forecast 220
Vectibix 222
Overview 222
Sales forecast 222
Denosumab (oncology) 224
Overview 224
Sales forecast 224
Pertuzumab 227
Overview 227
Sales forecast 228
Lumiliximab 229
Overview 229
Sales forecast 229
Ipilimumab 231
Overview 231
Sales forecast 231
Humax CD20 233
Overview 233
Sales forecast 233
Galiximab 235
Overview 235
Sales forecast 236
Campath/MAB Campath 237
Overview 237
Sales forecast 237
Mylotarg 239
Overview 239
Sales forecast 239
Rencarex 241
Overview 241
Sales forecast 241
Removab 243
Overview 243
Sales forecast 243
Zevalin 245
Overview 245
Sales forecast 245
Humax CD4 247
Overview 247
Sales forecast 247
Bexxar 249
Overview 249
Sales forecast 249
Humax EGFR 251
Overview 251
Sales forecast 251
Inotuzumab ozogamicin 253
Overview 253
Sales forecast 253
Theraloc 255
Overview 255
Sales forecast 255
Abagovomab 257
Overview 257
Sales forecast 257
Proxinium/Vicinium 259
Overview 259
Sales forecast 259
Immunology & inflammation 261
Humira 261
Overview 261
Sales forecast 261
Remicade 264
Overview 264
Sales forecast 264
Golimumab 267
Overview 267
Sales forecast 267
Actemra 269
Overview 269
Sales forecast 269
Cimzia 271
Overview 271
Sales forecast 271
Ocrelizumab 273
Overview 273
Sales forecast 273
Soliris 275
Overview 275
Sales forecast 275
Ustekinumab 277
Overview 277
Sales forecast 277
Rituxan/MabThera RA 279
Overview 279
Sales forecast 279
Mepolizumab 281
Overview 281
Sales forecast 281
Raptiva 283
Overview 283
Sales forecast 283
Simulect 285
Overview 285
Sales forecast 285
Canakinumab 287
Overview 287
Sales forecast 287
Epratuzumab 289
Overview 289
Sales forecast 289
ABT-874 291
Overview 291
Sales forecast 291
Zenapax 293
Overview 293
Sales forecast 293
Belimumab 295
Overview 295
Sales forecast 295
Reslizumab 297
Overview 297
Sales forecast 297
CNS 299
Bapineuzumab 299
Overview 299
Sales forecast 300
Tysabri 302
Overview 302
Sales forecast 302
MabThera/Rituxan (CNS) 304
Overview 304
Sales forecast 304
Campath/MAB Campath (CNS) 306
Overview 306
Sales forecast 306
Other 308
Lucentis 308
Overview 308
Sales forecast 309
Infectious diseases 311
Numax 311
Overview 311
Sales forecast 311
Synagis 313
Overview 313
Sales forecast 313
Aurograb 315
Overview 315
Sales forecast 315
Mycograb 317
Overview 317
Sales forecast 317
Musculoskeletal 319
Denosumab 319
Overview 319
Sales forecast 319
Respiratory 321
Xolair 321
Overview 321
Sales forecast 322
Cardiovascular 324
ReoPro 324
Overview 324
Sales forecast 325
Endocrine, metabolic and genetic disorders 326
Teplizumab 326
Overview 326
Sales forecast 327
CHAPTER 6 APPENDIX 328
Case studies: 'Big 5' mAb commercial evolution 328
Commercial evolution of Rituxan (CD20 market) 329
Commercial evolution of Remicade and Humira (TNF alfa market) 332
Commercial evolution of Herceptin (HER2 market) 336
Commercial evolution of Avastin (VEGF market) 339
Commercial evolution of the EGFR market 344
References 346
Datamonitor reports 346
List of Tables
Table 1: Summary of key changes 8
Table 2: PharmaVitae company coverage by peer set 11
Table 3: Molecule type definitions 16
Table 4: General characteristics of small molecule drugs vs. biologics 18
Table 5: Prescription pharmaceutical sales ($m) by molecule type, 2007-12 20
Table 6: Average revenues by molecule type, 2007 23
Table 7: The 'Big 5' (annual revenues >$3 billion in both 2007 and 2013) 33
Table 8: The 'Emerging 8' (>$500m growth 07-13) 35
Table 9: Overview of a selection of marketed mAbs: technology type and immunogenicity 75
Table 10: Infix nomenclature for mAbs 88
Table 11: Manufacturing cell lines for marketed mAbs 97
Table 12: Historical mAb product sales ($m), 2001-07 106
Table 13: Forecast mAb product sales ($m), 2007-13 112
Table 14: Historical mAb sales by company ($m), 2001-07 128
Table 15: Forecast mAb sales by company ($m), 2007-13 135
Table 16: Historical sales by therapy area ($m), 2001-07 143
Table 17: Forecast sales by therapy area ($m), 2007-13 146
Table 18: Historical sales by technology ($m), 2001-07 152
Table 19: Forecast sales by technology ($m), 2007-13 155
Table 20: Historical sales by target ($m), 2001-07 160
Table 21: Forecast sales by target ($m), 2007-13 165
Table 22: mAb pipeline overview 172
Table 23: Count of marketed mAbs 178
Table 24: Count of Phase III mAb players 181
Table 25: Count of companies with multiple Phase I-II mAb candidates 185
Table 26: mAb count split by technology type 189
Table 27: Count of mAb candidates by therapy area 195
Table 28: Detailed product/target analysis - late stage 198
Table 29: Novel late-stage targets 201
Table 30: Novel early-stage targets 203
Table 31: Companies with multiple novel early-stage targets 207
Table 32: The 'Big 5' targets and possible future entrants 209
Table 33: Avastin: overview 214
Table 34: Avastin global sales ($m), 2007-13 215
Table 35: Rituxan/MabThera: overview 216
Table 36: MabThera/Rituxan global sales ($m), 2007-13 216
Table 37: Herceptin: overview 218
Table 38: Herceptin global sales ($m), 2007-13 218
Table 39: Erbitux: overview 220
Table 40: Erbitux global sales ($m), 2007-13 220
Table 41: Vectibix: overview 222
Table 42: Vectibix global sales ($m), 2007-13 222
Table 43: Denosumab: overview 224
Table 44: Denosumab (oncology) global sales ($m), 2007-13 224
Table 45: Pertuzumab: overview 227
Table 46: Pertuzumab global sales ($m), 2007-13 228
Table 47: Lumiliximab: overview 229
Table 48: Lumiliximab global sales ($m), 2007-13 229
Table 49: Ipilimumab: overview 231
Table 50: Ipilimumab global sales ($m), 2007-13 231
Table 51: Humax CD20: overview 233
Table 52: Humax CD20 global sales ($m), 2007-13 233
Table 53: Galiximab: overview 235
Table 54: Galiximab global sales ($m), 2007-13 236
Table 55: MAB Campath: overview 237
Table 56: MAB Campath global sales ($m), 2007-13 237
Table 57: Mylotarg: overview 239
Table 58: Mylotarg global sales ($m), 2007-13 239
Table 59: Rencarex: overview 241
Table 60: Rencarex global sales ($m), 2007-13 241
Table 61: Removab: overview 243
Table 62: Removab global sales ($m), 2007-13 243
Table 63: Zevalin: overview 245
Table 64: Zevalin global sales ($m), 2007-13 245
Table 65: Humax CD4: overview 247
Table 66: Humax CD4 global sales ($m), 2007-13 247
Table 67: Bexxar: overview 249
Table 68: Bexxar global sales ($m), 2007-13 249
Table 69: Humax EGFR: overview 251
Table 70: Humax EGFR global sales ($m), 2007-13 251
Table 71: Inotuzumab ozogamicin: overview 253
Table 72: Inotuzumab ozogamicin global sales ($m), 2007-13 253
Table 73: Theraloc: overview 255
Table 74: Theraloc global sales ($m), 2007-13 255
Table 75: Abagovomab: overview 257
Table 76: Abagovomab global sales ($m), 2007-13 257
Table 77: Proxinium/Vicinium: overview 259
Table 78: Proxinium/Vicinium global sales ($m), 2007-13 259
Table 79: Humira: overview 261
Table 80: Humira global sales ($m), 2007-13 261
Table 81: Remicade: overview 264
Table 82: Remicade global sales ($m), 2007-13 264
Table 83: Golimumab: overview 267
Table 84: Golimumab global sales ($m), 2007-13 267
Table 85: Actemra: overview 269
Table 86: Actemra global sales ($m), 2007-13 269
Table 87: Cimzia: overview 271
Table 88: Cimzia global sales ($m), 2007-13 271
Table 89: Ocrelizumab: overview 273
Table 90: Ocrelizumab global sales ($m), 2007-13 273
Table 91: Soliris: overview 275
Table 92: Soliris global sales ($m), 2007-13 275
Table 93: Ustekinumab: overview 277
Table 94: Ustekinumab global sales ($m), 2007-13 277
Table 95: Rituxan/MabThera RA: overview 279
Table 96: MabThera/Rituxan RA global sales ($m), 2007-13 279
Table 97: Mepolizumab: overview 281
Table 98: Mepolizumab global sales ($m), 2007-13 281
Table 99: Raptiva: overview 283
Table 100: Raptiva global sales ($m), 2007-13 283
Table 101: Simulect: overview 285
Table 102: Simulect global sales ($m), 2007-13 285
Table 103: Canakinumab: overview 287
Table 104: Canakinumab global sales ($m), 2007-13 287
Table 105: Epratuzumab: overview 289
Table 106: Epratuzumab global sales ($m), 2007-13 289
Table 107: ABT-874: overview 291
Table 108: ABT-874 global sales ($m), 2007-13 291
Table 109: Zenapax: overview 293
Table 110: Zenapax global sales ($m), 2007-13 293
Table 111: Belimumab: overview 295
Table 112: Belimumab global sales ($m), 2007-13 295
Table 113: Reslizumab: overview 297
Table 114: Reslizumab global sales ($m), 2007-13 297
Table 115: Bapineuzumab: overview 299
Table 116: Bapineuzumab global sales ($m), 2007-13 300
Table 117: Tysabri: overview 302
Table 118: Tysabri global sales ($m), 2007-13 302
Table 119: MabThera/Rituxan (CNS): overview 304
Table 120: MabThera/Rituxan (CNS) global sales ($m), 2007-13 304
Table 121: MAB Campath (CNS): overview 306
Table 122: MAB Campath global sales ($m), 2007-13 306
Table 123: Lucentis: overview 308
Table 124: Lucentis global sales ($m), 2007-13 309
Table 125: Numax: overview 311
Table 126: Numax global sales ($m), 2007-13 311
Table 127: Synagis: overview 313
Table 128: Synagis global sales ($m), 2007-13 313
Table 129: Aurograb: overview 315
Table 130: Aurograb global sales ($m), 2007-13 315
Table 131: Mycograb: overview 317
Table 132: Mycograb global sales ($m), 2007-13 317
Table 133: Denosumab: overview 319
Table 134: Denosumab global sales ($m), 2007-13 319
Table 135: Xolair: overview 321
Table 136: Xolair global sales ($m), 2007-13 322
Table 137: ReoPro: overview 324
Table 138: ReoPro global sales ($m), 2007-13 325
Table 139: Teplizumab: overview 326
Table 140: Teplizumab global sales ($m), 2007-13 327
Table 141: Remicade vs. Enbrel key approvals 333
Table 142: Remicade vs. Enbrel key approvals 334
Table 143: The VEGF ligand and receptor targeting therapeutics 341
List of Figures
Figure 1: Updated mAb market forecast ($m), 2007-13 9
Figure 2: The total pharmaceutical market outlook, sales ($m) and year-on-year growth rate (%), 2001-13 13
Figure 3: Balance of launches and expiries in the prescription pharmaceutical market ($m), 2007-12 14
Figure 4: Absolute growth ($m) of PharmaVitae universe by molecule type 21
Figure 5: 2007-13 CAGRs of PharmaVitae universe by molecule type 22
Figure 6: Average revenue analysis by molecule type ($m), 2007 24
Figure 7: Sales growth drivers and resistors for mAbs, therapeutic proteins and small molecules 26
Figure 8: mAb market outlook, sales ($m) and year-on-year growth (%), 2007-13 28
Figure 9: Product analysis, historical and forecast sales growth ($m), 2001-13 29
Figure 10: Key mAb growth drivers & resistors ($m), 2007-13 31
Figure 11: Total market ($m) from the 'Big 5', 'Emerging 8' and others, 2001-13 37
Figure 12: Total market growth ($m) from the 'Big 5', 'Emerging 8' and others, 2007-13 38
Figure 13: Percentage contribution to sales from the 'Big 5' and 'Emerging 8' in 2007 and 2013 39
Figure 14: Company analysis, historical and forecast sales growth ($m), 2001-13 40
Figure 15: Therapy area analysis, historical and forecast sales growth ($m), 2001-13 42
Figure 16: Technology analysis, historical and forecast sales growth ($m), 2001-13 44
Figure 17: Target analysis, historical and forecast sales growth ($m), 2001-13 45
Figure 18: Idealized mAb model 51
Figure 19: Protein domain structures of key receptor/ligand pairs in the mAb market 55
Figure 20: Conceptual map of the commercial mAb landscape in 2013 58
Figure 21: The structure of an antibody 66
Figure 22: Types of antibodies 74
Figure 23: Immunogenicity ranges 76
Figure 24: Number of marketed mAb technologies 77
Figure 25: Schematic illustration of antibody fragments 83
Figure 26: Number of marketed full length mAbs versus fragments 84
Figure 27: Number of marketed naked and conjugated mAbs 87
Figure 28: mAb timeline - technology shift 90
Figure 29: The monoclonal antibody market, 2001-07 102
Figure 30: The monoclonal antibody market, 2007-13 103
Figure 31: mAb product sales ($m) 2001-13 104
Figure 32: Growth driver/resistor products of historical revenue performance ($m), 2001-07 108
Figure 33: Growth driver/resistor products of forecast revenue performance ($m), 2007-13 115
Figure 34: mAb company sales ($m), 2001-13 126
Figure 35: Growth driver/resistor companies of historical revenue performance ($m), 2001-07 129
Figure 36: Growth driver/resistor companies of forecast revenue performance ($m), 2007-13 137
Figure 37: mAb therapy area sales ($m) 2001-13 141
Figure 38: Growth driver/resistor therapy areas of historical revenue performance ($m), 2001-07 144
Figure 39: Growth driver/resistor therapy areas of forecast revenue performance ($m), 2007-13 147
Figure 40: mAb technology sales ($m), 2001-13 151
Figure 41: Growth driver/resistor technologies of historical revenue performance ($m), 2001-07 153
Figure 42: Growth driver/resistor technologies of historical revenue performance ($m), 2007-13 156
Figure 43: mAb target sales ($m), 2001-13 159
Figure 44: Growth driver/resistor targets of historical revenue performance ($m), 2001-07 161
Figure 45: Growth driver/resistor targets of forecast revenue performance ($m), 2007-13 166
Figure 46: Count of marketed mAb players 179
Figure 47: Count of Phase III pipeline mAb players 182
Figure 48: Count of companies with multiple Phase I-II mAb candidates 186
Figure 49: Phase I-III pipeline count split by technology 190
Figure 50: The stepwise evolution of naked mAb technology 191
Figure 51: Overview of pipeline technology type Phase I-registration 192
Figure 52: Emerging mAb technologies (% mAb candidates) 194
Figure 53: Phase I-pre-reg mAb count split by therapy area 196
Figure 54: Count of the most popular targets in early-stage development 206
Figure 55: Commercial evolution of the CD20 market 329
Figure 56: Commercial evolution of the TNF alfa market 332
Figure 57: Commercial evolution of the HER2 market 336
Figure 58: Commercial evolution of the VEGF/VEGFR market 339
Figure 59: Commercial evolution of the EGFR market 344