Analysis of the Pharmaceutical Market to 2012 - Segmented by Drug Target Family

CHAPTER 1 EXECUTIVE SUMMARY 4
Key findings 4
Introduction to the PharmaVitae universe 5
The outlook for the market is challenging 6
Market performance is shaped by key ATC classes 7
The three fundamental dimensions of pharma space 8
Dimension one: molecule type analysis 8
MAbs and therapeutic proteins to provide the greatest overall sales growth 8
Generic erosion wipes out small molecule drug sales 9
mAbs driven by 'core' sales 11
Dimension two: therapy area analysis 12
Oncology and AIID products drive growth across 2006-12 12
GI and CV particularly badly hit in 2012 13
Targets provide a missing link between drugs and disease 15
Target classification 16
Dimension three: target family analysis 17
ECS target family set for superior performance 17
Only the ECS target family will see growth between 2011-12 (the 'patent cliff') 18
Position within the three fundamental dimensions of pharma space influences commercial outlook 20
Introduction 20
Novel targets offer reduced competitive pressures 20
Superior commercial outlook with increasing target novelty 20
New technologies allow expansion into novel target space 21
Market growth driven by biologics acting on ECS targets 22
Biologics offer insulation from generic erosion 23
ECS shielded from generics 23
Lifecycle stage dictates performance of small molecule drugs 24
Areas of high unmet need facilitate commercial success 26
Biologics more warranted in areas of high unmet need 26
Certain areas already saturated by cheap options 27
Perfomance relates to the balance of key characteristics 28
Commercial attractiveness characteristics 28
Not all volumes of pharma space are biologically viable 29
Mechanism of disease dictates the pharmacologically useful targets 29
Small molecule drugs cannot modulate ECS targets 30
Biologics cannot access the targets relating to certain diseases 30
ATC performance is driven by key characteristics 31
Segment 1: High growth biologics 34
Segment 2: Declining small molecule drugs 34
Segment 3: High growth small molecule drugs 35
Considerations beyond 2012 37
The need for new technologies 37
DNA/RNA therapies hit the central dogma of biology 38
Gene therapy 39
RNA therapies 40
CHAPTER 2 MARKET ANALYSIS 46
Key findings 46
Introduction 47
Total market overview 48
Growth drivers and resistors 49
Top 25 growth drivers across 2006-12 49
Top 25 growth resistors across 2006-12 50
Top 25 growth drivers 2012 51
Top 25 growth resistors 2012 52
Molecule type analysis 53
Small molecule drugs account for the bulk of sales 53
Generic substitution is greater where more generic alternatives are available 54
Products satisfying high unmet needs are more likely to gain market share 55
Biologic products will make a greater contribution to growth 55
Therapy area analysis 57
Therapy area growth drivers and resistors 57
Oncology and AIID drive growth 58
CV and GI set to decline overall 58
2006-11 performance 60
2012 performance 61
LCE profile 62
CHAPTER 3 TARGET FAMILY CLASSIFICATION 64
Key findings 64
Introduction 65
Targets are a key dimension of pharma space 65
The druggable genome 66
Druggability by small molecules-the Rule of Five. 67
Target family classification 68
GPCR target family 69
Introduction 69
Structure and function 69
Subfamilies 70
Ion channel target family 71
Introduction 71
Structure and function 71
Subfamilies 72
Nuclear receptor target family 73
Introduction 73
Structure and function 73
Subfamilies 74
Enzyme target family 75
Introduction 75
Structure and function 75
Subfamilies 76
Extracellular signaling (ECS) target family 77
Introduction 77
Structure and function 77
Subfamilies 78
Non-human 79
Other 79
Mixed 79
Unclassified 79
CHAPTER 4 MARKET ANALYSIS BY TARGET FAMILY 80
Key findings 80
Overview 81
Target family performance 81
ECS target family driving overall market growth 84
Enzyme and GPCR target families take the greatest hit in 2012 85
Therapy area analysis: satisfaction of unmet needs drives success 87
GPCR targets take the largest share of the CV and CNS sales 88
CV therapy area set for 'boom and bust' 88
Without target innovation, CNS products struggle to offset expiries 89
ECS targets drive growth of the oncology and AIID therapy areas 91
Falling sales of enzyme modulators bring down GI 93
Molecule type analysis 94
Monoclonal antibody (mAb) sales are driven by ECS targets 95
Therapeutic protein analysis 97
Small molecule drugs are highly susceptible to generic erosion 99
Vaccine sales are entirely derived from non-human targets 101
LCE analysis 103
Launch 104
Core 107
Expiry 109
CHAPTER 5 NUCLEAR RECEPTOR AND ION CHANNEL TARGET FAMILIES 111
Key findings 111
Overview: nuclear receptor and ion channel target families 112
Contribution to total market sales is set to diminish further 113
Ranked amongst the smallest target families by sales 113
Forecast to experience the fastest rate of decline 114
Scope for expansion is restricted 115
Small number of possible nuclear receptor target types 115
Nuclear receptors are not readily targeted by biologics 115
Ion channels offer significant potential, but are limited by their high association with CNS disorders 115
Therapy area analysis: key areas dictate overall performance 116
Diabetes & endocrinology pulls down nuclear receptor-related sales 116
Diabetes sales are pulled down by genericization of just one target type 117
Women's health products generate growth for the nuclear receptor target family 118
Growth despite limited target innovation 118
Tougher times ahead? 120
CNS pulls down ion channels 121
CNS is the largest ion channel therapy area by sales 121
New launches are not sufficient to overcome the decline of older products 122
Competition high due to lack of target innovation 123
Products not revolutionizing the satisfaction of unmet needs 125
Molecule type analysis: exclusively small molecule 126
LCE analysis: expiries drag sales into decline 128
CHAPTER 6 EXTRACELLULAR SIGNALLING PROTEIN (ECS) TARGET FAMILY 130
Key findings 130
Overview: ECS target family 131
Fastest rate of growth over 2006-12 132
Only target family to see growth in 2012 133
Therapy area analysis: driving growth of AIID & oncology 135
AIID sales growth is entirely reliant on ECS targets 137
Sales are largely derived from products acting on TNF-α 139
Novel targets generate growth as anti-TNF market slows 140
Novel ECS targets drive oncology growth 141
Success drawn from 'locking competitors out' of key targets 142
Molecule type analysis: new technologies opened up ECS targets 144
MAb technology has allowed novel ECS targets to be exploited 145
Unique position compared to other target families 146
Potential small molecule threat? 147
LCE analyis: growth across all LCE components 148
Expansion through novel targets 149
Free from declining 'expiry' sales 149
CHAPTER 7 ENZYME AND GPCR TARGET FAMILIES 151
Key findings 151
Overview: enzyme and GPCR target families 152
The largest target families by sales 153
Forecast to see the greatest decline over 2011-12 155
Therapy area analysis: novel targets drive growth 157
Enzyme sales growth wiped out by declining therapy areas. 157
Novel targets drive oncology sales and the enzyme target family 159
Transferase targets drive oncology therapy area growth 159
Tyrosine kinase inhibitors exemplify novel target value 160
Tyrosine kinase inhibitors account for the bulk of enzyme target family gains 161
GI and CV sales hit by loss of patents on key classes 162
Heavily reliant on ageing PPIs, GI sales are set decline 162
HMG-CoA reductase inhibitors erode enzyme target family growth 163
GPCR sales growth across all therapy areas but eroded in 2012 165
Angiotensin II receptor antagonists drive CV growth but hit by genericization 166
New CNS launches do little to replace the loss of 'blockbusters' 167
Diabetes sales driven by novel targets 168
Molecule type analysis: almost entirely small molecule 169
LCE analysis: expiries offset growth 171
Significant 'launch' gains driven by availability of novel targets 172
Massive 'expiry' loss in 2012 173
CHAPTER 8 APPENDIX 174
Target sub-sub-families 174
GPCR sub-sub-families 174
Nuclear receptor sub-sub-families 177
Enzyme sub-sub-families 178
Details of mixed and unclassified 180
Avandia 180
References 181
Journals 181
Websites 182
Abbreviations 183
List of Tables
Table 1: PharmaVitae company coverage by peer set 5
Table 2: Target family classification 16
Table 3: Datamonitor's commercial attractiveness characteristics 31
Table 4: Top 25 growth drivers, 2006-12 ($m) 49
Table 5: Top 25 growth resistors, 2006-12 ($m) 50
Table 6: Top 25 growth drivers, 2011-12 ($m) 51
Table 7: Top 25 growth resistors, 2011-12 ($m) 52
Table 8: Target family classification 68
Table 9: GPCR subfamilies 70
Table 10: Ion channel subfamilies 72
Table 11: Nuclear receptor subfamilies 74
Table 12: Enzyme superfamilies 76
Table 13: ECS subfamily classification 78
Table 14: GPCR sub-sub-families 174
Table 15: Nuclear receptor sub-sub-families 177
Table 16: Enzyme sub-sub-families 178
List of Figures
Figure 1: Pharmaceutical market performance, sales ($m) and year-on-year growth (%), 2006-12 6
Figure 2: Top 10 growth driver/resistor ATC classes 7
Figure 3: Change in total market sales by molecule type, 2006-12 ($m) 9
Figure 4: Molecule type sales growth by LCE stage, 2006-12 (%) 10
Figure 5: Change in total market sales by therapy area, 2006-12 ($m) 12
Figure 6: Dynamics of key therapy area sales, 2006-12 ($m) 14
Figure 7: Three dimensions of pharma space 15
Figure 8: Change in total market sales by target family, 2006-12 ($m) 17
Figure 9: Target family growth rates, 2006-12 (CAGR %) 18
Figure 10: Change in total market sales by target family, 20011-12 ($m) 19
Figure 11: Technological advances expand the 'druggable' space 21
Figure 12: Molecule type sales by target family, 2006 (%) 22
Figure 13: Change in year-on-year sales by LCE stage, 2006-12 ($m) 25
Figure 14: Therapy area sales by target family, 2006 ($m) 27
Figure 15: Key characteristics influencing commercial attractiveness 28
Figure 16: Factors limiting the exploitable pharma space 29
Figure 17: Key ATC class outlook and position against commercial attractiveness characteristics, change in sales 2006-12 32
Figure 18: Key market segments, 2006-12 33
Figure 19: The central dogma of biology and potential role of DNA/RNA therapies in relation to traditional 'drugging' approaches 39
Figure 20: Gene 'silencing' by short interefering RNA (siRNA) 41
Figure 21: Report structure 47
Figure 22: Total market sales, 2003-12 ($m) 48
Figure 23: Total market sales by molecule type, 2003-12 ($m) 53
Figure 24: Substitution of branded small molecule drugs for generics 54
Figure 25: Change in total market sales by molecule type, 2006-12 ($m) 56
Figure 26: Total market sales by therapy area, 2003-12 ($m) 57
Figure 27: Change in total market sales by therapy area, 2006-12 ($m) 59
Figure 28: Change in total market sales by therapy area, 2006-11 ($m) 60
Figure 29: Change in total market sales by therapy area, 2011-12 ($m) 61
Figure 30: Change in total market sales by LCE stage, 2006-12 ($m) 62
Figure 31: Change in year-on-year sales by LCE stage, 2006-12 ($m) 63
Figure 32: The role of drug targets in disease treatment 65
Figure 33: The commercially useful subset of the human genome 66
Figure 34: GPCRs structure 69
Figure 35: Functional architecture of an ion channel 71
Figure 36: Structural organization of nuclear receptors 73
Figure 37: Epidermal growth factor receptor (EGFR) structure 77
Figure 38: Total market sales by target family, 2006 ($m) 82
Figure 39: Target family sales CAGR, 2006-12 (%) 83
Figure 40: Total market sales by target family, 2006-12 ($m) 84
Figure 41: Total market sales by target family, 2011-12 ($m) 85
Figure 42: Year-on-year change in target family sales, weighted as a proportion of change in total sales, 2004-12 (%) 86
Figure 43: CV therapy area sales by target family, 2003-12 ($m) 88