ABOUT DATAMONITOR HEALTHCARE 2
About the PharmaVitae team 2
Chapter 1 About this Sector Report 3
PharmaVitae Explorer database 3
Chapter structure 3
Executive summary 3
mAb technology overview 3
Market analysis 3
Pipeline analysis 4
Key products 4
Data sourcing 4
Sales data 4
Chapter 2 Executive summary 5
Key findings 5
Total prescription pharmaceutical market outlook 5
Monoclonal antibody market outlook 6
Introduction to the PharmaVitae company universe 7
The prescription pharmaceutical market to 2014 10
Prescription pharmaceutical market performance, 2008-14 10
Introduction to molecule type analysis 11
Small molecules 12
Therapeutic proteins 12
Monoclonal antibodies 12
Vaccines 12
Industry consequences of molecule type 12
Prescription pharmaceutical sales by molecule type, 2008-14 14
The monoclonal antibody market will deliver the biggest portion of sales growth across the entire pharmaceutical industry, at the fastest rate 14
The mAb market is forecast to increase at a double-digit growth rate 17
The monoclonal antibody market will deliver much-needed sales growth in order to offset US-centered small molecule sales collapse 18
Geographic sales growth: the US and 5EU lead the way 21
A raft of new mAbs expected to make it onto the market over 2008-14... 24
...but still only a few mAbs command the highest revenues 25
Introduction to the 'Big 5' 26
'Big 5' dominance will remain, although their share will decline 27
Product analysis (size) 28
Product analysis (growth) 29
Company analysis 31
Big Pharma's hold on the mAb market 33
Recent M&A deals underline Pharma's 'bankable view' of mAbs 35
The mAb landscape: innovation driven by collaboration and M&A 37
Long term opportunities and threats 40
Long term threat of biosimilar mAbs? 40
The US offers the 'biggest biosimilar prize' 40
Price of mAb therapies a major resistor to growth, however, the collapse of the US branded small molecule market could 'free-up' payer resource to expand mAb purchasing 41
Drive for personalized medicine: the role of companion diagnostics, an opportunity for diagnostic and mAb players 41
Table of Contents 42
Table of figures 44
Chapter 3 MAb Technology Overview 45
Key findings 45
Introduction 46
The immune system 46
B lymphocytes and antibodies 46
Antibody structure 46
Hybridoma technique - the production of mAbs 48
Monoclonal antibodies as therapeutic agents 48
Targets 48
Target selection - the importance of an accessible epitope 49
Production of mAbs 49
Transgenic mice 49
Phage display 50
Future focus 50
Mode of action 51
mAb-focused oncology 51
The effect of the effector region 51
Blockade 51
MAbs as a delivery vehicle 52
Evolution of mAbs 52
Limitations associated with immunization 52
Murine 57
Chimeric and humanized antibodies 57
Chimeric 57
Humanized 58
Fully human 59
Fragments 59
Conjugated 60
Radiolabeled conjugated mAbs 60
Focus for antibody R&D - oncology immunotoxin drug conjugates 61
Naked mAbs still dominate 62
Systematic naming of monoclonal antibodies 63
The mAb timeline - technology evolution 63
Manufacturing 68
Time to market and manufacturing of monoclonal antibodies 68
Mammalian cell culture - still the most widely-used system 68
Chapter 4 Market analysis 72
Key findings 72
Introduction 73
The mAb market, overview of the fastest growing sector across the pharmaceutical industry 73
The mAb market: the double-digit growth market 75
Key global mAb products, 2002-14 75
Introduction to the 'Big 5' 76
MAb market: product analysis, 2002-14 77
Historical product analysis, 2002-08 79
Growth from a few 80
Rapid uptake from two key therapies 81
Growth continues from more established therapies 82
Forecast product analysis, 2008-14 84
Avastin to shape the mAb market future 86
Humira will be the biggest immunology & inflammation driver 87
Still growth left for the older brands 88
Exciting Amgen entrant to make an impact 89
Second generation anti-TNF to gain some ground on Humira... 89
...at the expense of Remicade 90
Innovative Alzheimer's therapy attracts additional Big Pharma investment 90
Roche expands mAb interests away from oncology 91
MAb market: company analysis, 2002-14 92
Historical product analysis, 2002-08 93
'Big 5' ownership highlights four key players 94
Genentech and Roche: the symbiotic partnership 94
Abbott Laboratories, growth through in-licensing 95
Schering Plough and Johnson & Johnson: Remicade centered growth 95
Forecast company analysis, 2008-14 96
Leading players will maintain standing, with few new entrants 97
Roche through Genentech maintains leading position 98
Abbott's Humira-centric growth 98
Amgen: the emerging player 99
Johnson & Johnson, recent deal boosts mAb interests 99
MAb market: therapy area analysis, 2002-14 100
Historical therapy area analysis, 2002-08 101
'Big Three' drives oncology sales 102
Immunology & inflammation: two-product therapy area 103
Forecast therapy area analysis, 2008-14 103
Oncology: Genentech/Roche continue to lead the way 105
Immunology & inflammation delivers strong growth, despite Raptiva withdrawal 106
After a stuttering start central nervous system will emerge as a major mAb therapy area 107
Musculoskeletal 107
MAb market: geographic analysis, 2002-14 109
Historical geographic analysis, 2002-08 110
US growth centered on 'Big 5' 110
Herceptin drives 5EU sales 110
Japan: older therapies in an earlier life cycle stage 110
Forecast geographic analysis, 2008-14 111
The US and 5EU will contribute almost 80% of the global mAb market growth 112
The developing Japanese market will experience some major brand launches... 113
... but the RoW will still generate more mAb sales 113
MAb market: technology analysis, 2002-14 114
Historical technology analysis, 2002-08 115
Humanized becomes the number one in 2008 115
Forecast technology analysis, 2008-14 116
Increasing human content the market driver 116
Avastin and key launch products will drive humanized sales 117
Human mAb sales growth centered on three products 118
The once dominant chimeric mAbs will slow in growth 118
Antibody fragments, the only other +$1 billion sales growth driver 119
MAb market: target analysis, 2002-14 120
Historical target analysis, 2002-08 121
Forecast target analysis, 2008-14 122
Avastin and Lucentis will drive VEGF sales 124
Well represented TNF alpha target will continue to grow 124
CD20: Rituxan remains dominant although GSK will make some headway 124
RANKL sales growth from highly anticipated first-in-class Prolia 125
Market withdrawal of Raptiva in 2009 ends CD11a sales growth 125
Chapter 5 Pipeline analysis 126
Key findings 126
Introduction 127
MAb pipeline overview 128
Company pipeline analysis 135
Late-stage company pipeline analysis 137
Early-stage company pipeline analysis 140
Change of direction driven by acquisition 141
Technology pipeline analysis 143
Therapy area pipeline analysis 147
Target pipeline analysis 150
Target crowding evident with the late-stage mAbs - with lifecycle management strategies being employed 151
Novel target early-stage candidates 153
Chapter 6 Key products 159
Key findings 159
Introduction 160
Oncology 161
Avastin 161
Overview 161
Sales forecast 162
Product overview 162
Additional indication approvals drives growth 162
Failure in adjuvant trial raises concerns 163
Competitive threats to future sales growth 164
Herceptin 165
Overview 165
Sales forecast 166
Product overview 166
Competitive threats to future sales growth 167
MabThera/Rituxan 169
Overview 169
Sales forecast 170
Product overview 170
Competitive threats to future sales growth 171
Erbitux 172
Overview 172
Sales forecast 173
Restrictive patient population impedes sales growth 173
Additional indications drive growth 174
Prolia (onco) 176
Overview 176
Sales forecast 177
Prolia (oncology) 177
Significant opportunity in oncology, targeting Zometa's market 177
Amgen initially seeking approval for treatment of bone loss in patients receiving hormone ablation chemotherapy 178
Biggest sales potential lies within the treatment and prevention of bone metastasis 178
Amgen announces positive late-stage bone metastases data 178
Vectibix 180
Overview 180
Sales forecast 181
Personalized medicine movement to boost sales? 181
Arzerra 183
Overview 183
Sales forecast 184
Genmab/GlaxoSmithKline are investigating Arzerra in the first-line follicular lymphoma setting 184
Genmab/GlaxoSmithKline's commercial strategy may improve Arzerra's chances of success in the non-Hodgkin's lymphoma market 184
Targeting underserved chronic lymphocytic leukemia patients may enhance Arzerra's uptake in the market; gains FDA approval 185
Immunology & inflammation 186
Humira 186
Overview 186
Sales forecast 187
First fully human anti-TNF alpha mAb 187
Aggressive indication broadening 187
Humira growth outstrips rivals Enbrel and Remicade 188
Significant dosing and delivery advantages help drive uptake 188
Further growth across all indications expected despite new launches 188
Remicade 189
Overview 189
Sales forecast 190
Remicade can be used at first-line without prior failure of methotrexate 190
Remicade is prescribed in patients who may have compliance problems 191
Unlike Enbrel and Humira, Remicade does not have the JIA indication 191
Remicade's sales will decrease from 2010 as patients shift to Simponi 191
Simponi 192
Overview 192
Sales forecast 193
Simponi will be positioned in multiple rheumatoid arthritis patient subgroups 193
Simponi and first-generation Remicade will compete in the same rheumatoid arthritis populations 193
Simponi offers dosing frequency advantages over other TNF inhibitors 194
Cimzia 196
Overview 196
Sales forecast 197
UCB's novel anti-TNF mAb finally gets green light 197
UCB faces a considerable promotional hurdle in recruiting physicians 197
Non-responder patient population and pricing offer key route to uptake 198
Actemra 199
Overview 199
Sales forecast 200
Product overview 200
Delay to launch in the US 201
Actemra has strong positioning potential as a result of impressive Phase III program 201
Product positioning 201
Future performance 201
Stelara 203
Overview 203
Sales forecast 204
Compared to Enbrel, Stelara shines in terms of efficacy 204
Dosing frequency distinguishes Stelara from marketed biologics 205
Central nervous system 206
Tysabri 206
Overview 206
Sales forecast 207
Product overview 207
Safety scare 207
Re-launch 208
Two new confirmed cases of PML rocks initially strong 2008 Tysabri uptake 208
Physician enrollment and patient numbers have increased strongly with each month through to July 2008 209
Long-term growth hinges on the incidence and management of new PML cases 209
Bapineuzumab 210
Overview 210
Sales forecast 211
Product overview 211
Campath (CNS) 213
Overview 213
Sales forecast 214
Product overview 214
Phase II data show superior efficacy compared to Rebif 214
Safety concerns 215
Future market potential 215
Infectious diseases 217
Numax 217
Overview 217
Sales forecast 218
Product overview 218
Synagis 219
Overview 219
Sales forecast 220
Product overview 220
Respiratory 221
Xolair 221
Overview 221
Sales forecast 222
Musculoskeletal 223
Prolia 223
Overview 223
Sales forecast 224
First-in-class therapy 224
Not oral, but convenient dosing all the same 225
Strong clinical trial data, issues regarding safety 225
Initially positioned as a second-line therapy 226
GSK deal should provide Amgen with higher returns 226
Cardiovascular 227
ReoPro 227
Overview 227
Sales forecast 228
Other 229
Lucentis 229
Overview 229
Sales forecast 230
Fragment of Avastin has provided significant revenues 230
Strong clinical trial data has positioned Lucentis as the market leading treatment 230
Avastin off-label usage discouraged 230
Chapter 7 Appendix 232
References 232
Datamonitor reports 232
Abbreviations 233
Exchange rates 234
About Datamonitor 235
About Datamonitor Healthcare 235
Datamonitor consulting 235
Disclaimer 237
List of Tables
Table 1: PharmaVitae company coverage by peer set 8
Table 2: Molecule type definitions 11
Table 3: General characteristics of small molecule drugs vs. biologics 13
Table 4: Prescription pharmaceutical sales ($m) by molecule type, 2008-14 14
Table 5: The global small molecule market ($m), 2008-14 18
Table 6: The global mAb market ($m), 2008-14 20
Table 7: The 'Big 5' (annual revenues >$4 billion in both 2008 and 2014) 26
Table 8: Overview of a selection of marketed mAbs: technology type and immunogenicity 54
Table 9: Infix nomenclature for mAbs 63
Table 10: Manufacturing cell lines for marketed mAbs 70
Table 11: Global top 5: 2002, 2008 & 2014 ($m) 75
Table 12: The 'Big 5' (annual revenues >$4 billion in both 2008 and 2014) 76
Table 13: Historical mAb product sales ($m), 2002-08 79
Table 14: Forecast mAb product sales ($m), 2008-14 84
Table 15: Historical mAb company sales ($m), 2002-08 93
Table 16: Forecast mAb company sales ($m), 2008-14 96
Table 17: Historical mAb therapy area sales ($m), 2002-08 101
Table 18: Forecast mAb therapy area sales ($m), 2008-14 104
Table 19: Historical mAb geography sales ($m), 2002-08 110
Table 20: Forecast mAb geography sales ($m), 2008-14 111
Table 21: Historical mAb technology sales ($m), 2002-08 115
Table 22: Forecast mAb technology sales ($m), 2008-14 116
Table 23: Historical mAb target sales ($m), 2002-08 121
Table 24: Forecast mAb target sales ($m), 2008-14 122
Table 25: MAb pipeline overview 128
Table 26: Count of marketed mAbs 135
Table 27: Count of Phase III mAb players 137
Table 28: Count of companies with multiple Phase I-II mAb candidates 140
Table 29: mAb count split by technology type 143
Table 30: mAb count split by technology type 147
Table 31: Detailed product/target analysis - late stage 150
Table 32: Novel late-stage targets 152
Table 33: Novel early-stage targets 154
Table 34: Avastin: overview 161
Table 35: Avastin: sales forecast ($m), 2008-14 162
Table 36: Herceptin: overview 165
Table 37: Herceptin: sales forecast ($m), 2008-14 166
Table 38: MabThera/Rituxan: overview 169
Table 39: MabThera/Rituxan: sales forecast ($m), 2008-14 170
Table 40: Erbitux: overview 172
Table 41: Erbitux: sales forecast ($m), 2008-14 173
Table 42: Prolia (onco): overview 176
Table 43: Prolia (onco): sales forecast ($m), 2008-14 177
Table 44: Vectibix: overview 180
Table 45: Vectibix: sales forecast ($m), 2008-14 181
Table 46: Arzerra: overview 183
Table 47: Arzerra: sales forecast ($m), 2008-14 184
Table 48: Humira: overview 186
Table 49: Humira: sales forecast ($m), 2008-14 187
Table 50: Remicade: overview 189
Table 51: Remicade: sales forecast ($m), 2008-14 190
Table 52: Simponi: overview 192
Table 53: Simponi: sales forecast ($m), 2008-14 193
Table 54: Comparison of the route of administration and dosing frequency of the anti-TNFs in rheumatoid arthritis 194
Table 55: Cimzia: overview 196
Table 56: Cimzia: sales forecast ($m), 2008-14 197
Table 57: Actemra: overview 199
Table 58: Actemra: sales forecast ($m), 2008-14 200
Table 59: Stelara: overview 203
Table 60: Stelara: sales forecast ($m), 2008-14 204
Table 61: Tysabri: overview 206
Table 62: Tysabri: sales forecast ($m), 2008-14 207
Table 63: Bapineuzumab: overview 210
Table 64: Bapineuzumab: sales forecast ($m), 2008-14 211
Table 65: Campath (CNS): overview 213
Table 66: Campath (CNS): sales forecast ($m), 2008-14 214
Table 67: Numax: overview 217
Table 68: Numax: sales forecast ($m), 2008-14 218
Table 69: Synagis: overview 219
Table 70: Synagis: sales forecast ($m), 2008-14 220
Table 71: Xolair: overview 221
Table 72: Xolair: sales forecast ($m), 2008-14 222
Table 73: Prolia: overview 223
Table 74: Prolia: sales forecast ($m), 2008-14 224
Table 75: ReoPro: overview 227
Table 76: ReoPro: sales forecast ($m), 2008-14 228
Table 77: Lucentis: overview 229
Table 78: Lucentis: sales forecast ($m), 2008-14 230
Table 79: Exchange rates, 2009 234
List of Figures
Figure 1: The PharmaVitae Explorer 3
Figure 2: The total pharmaceutical market outlook, sales ($m) and year-on-year growth rate (%), 2002-14 10
Figure 3: Change in annual sales from 2008-14 ($m) of PharmaVitae universe by molecule type 15
Figure 4: Compound annual growth rate (%) of PharmaVitae universe by molecule type 16
Figure 5: Total sales of the mAb market ($m), 2002-14 17
Figure 6: The US versus ex-US small molecule market sales growth ($m), (%), 2002-14 19
Figure 7: The US versus ex-US monoclonal antibody market sales growth ($m), (%), 2002-14 20
Figure 8: mAb market geographic analysis, total sales ($m), 2002-14 22
Figure 9: Total number of mAbs versus total mAb market sales ($m), 2002-14 24
Figure 10: Total mAb sales versus average price per mAb ($m), 2002-14 25
Figure 11: Sales proportion of the 'Big 5' vs the rest of the mAb market (%), 2002-14 27
Figure 12: mAb product sales ($m), 2002-14 28
Figure 13: Growth driver/resistor products of forecast revenue performance ($m), 2008-14 29
Figure 14: MAb company sales ($m), 2002-14 31
Figure 15: mAb ownership sales by peer set ($,%), 2002-14 33
Figure 16: Big Pharma's $74 billion worth of key mAb acquisitions over the past five years 35
Figure 17: The collaborative landscape of the mAb market key players 37
Figure 18: The structure of an antibody 47
Figure 19: Types of antibodies 53
Figure 20: Immunogenicity ranges 55
Figure 21: Number of marketed mAb technologies 56
Figure 22: Schematic illustration of antibody fragments 60
Figure 23: mAb timeline - technology shift 64
Figure 24: Total sales of the mAb market ($m), 2002-14 74
Figure 25: MAb product sales ($m), 2002-14 77
Figure 26: Growth driver/resistor products of historical revenue performance ($m), 2002-08 81
Figure 27: Growth driver/resistor products of forecast revenue performance ($m), 2008-14 86
Figure 28: MAb company sales ($m), 2002-14 92
Figure 29: Growth driver/resistor companies of historical revenue performance ($m), 2002-08 94
Figure 30: Growth driver/resistor companies of forecast revenue performance ($m), 2008-14 98
Figure 31: MAb therapy area sales ($m), 2002-14 100
Figure 32: Growth driver/resistor therapy areas of historical revenue performance ($m), 2002-08 102
Figure 33: Growth driver/resistor therapy areas of forecast revenue performance ($m), 2008-14 105
Figure 34: MAb geography sales ($m), 2002-14 109
Figure 35: Growth driver/resistor geographies of forecast revenue performance ($m), 2008-14 112
Figure 36: MAb technology sales ($m), 2002-14 114
Figure 37: Growth driver/resistor technologies of forecast revenue performance ($m), 2008-14 117
Figure 38: MAb target sales ($m), 2002-14 120
Figure 39: Growth driver/resistor targets of forecast revenue performance ($m), 2008-14 123
Figure 40: Count of marketed mAb players 136
Figure 41: Count of Phase III pipeline mAb players 138
Figure 42: Count of companies with multiple Phase I-II mAb candidates 141
Figure 43: Phase I-III pipeline count split by technology 144
Figure 44: The stepwise evolution of naked mAb technology 145
Figure 45: Overview of pipeline technology type Phase I-registration 146
Figure 46: Phase I-pre-reg mAb count split by therapy area 148
Figure 47: Count of the most popular targets in early-stage development 158
