Table of Contents
ABOUT DATAMONITOR HEALTHCARE 2
About the Women's Health pharmaceutical analysis team 2
CHAPTER 1 EXECUTIVE SUMMARY 3
Scope of the analysis 3
Contributing experts 4
Datamonitor insight into the urinary incontinence market 4
Related reports 7
CHAPTER 2 MARKET OVERVIEW AND POTENTIAL 9
Market and disease definition 10
Normal bladder function 10
Urinary Incontinence 10
Relationship between overactive bladder and UI 11
"Wet" overactive bladder is a form of urge UI 11
Dry overactive bladder can impact on quality of life 12
Definition of urinary incontinence market 13
Market potential 14
Epidemiology of UI 14
Prevalence of UI 14
Prevalence high, but treatment rates are likely to be low 14
Stress urinary incontinence is the most common form of UI 15
Patient population with UI likely to rise with the ageing of the general population 16
Etiology of UI 17
Urge UI symptoms from overactive bladder 17
Stress urinary incontinence 17
Mixed urinary incontinence 18
Unmet need in UI 18
Efficacy in controlling symptoms 18
Reduction of side-effect profile 18
Alternative delivery mechanism 21
Reduced pill burden 21
Alternative targets 22
Stress urinary incontinence 22
Current treatment classes and mechanisms 24
Treatment algorithm 24
Behavioral techniques 24
Pharmacological treatment 25
Medical devices 26
Surgery 27
Current market value and future market forecasts 28
Current market dynamics 28
Anticholinergics dominate current market 28
The US generated more revenue from UI therapies than the EU and Japan combined 29
The UI market is set to grow throughout the forecast period 30
Near-term growth-reformulations 31
Medium-term growth-life-cycle management strategies, novel products and new markets 32
Long-term outlook-patent expiries take their toll 32
CHAPTER 3 BRAND DYNAMICS AND LEADING COMPARATOR THERAPIES 33
Marketed brands overview 34
Detrol (LA) (tolterodine) 35
Drug overview 35
Forecasts to 2016 37
SWOT analysis 39
Clinical trial data 39
Detrol's clinical trial program and study designs 39
Efficacy of Detrol 40
Detrol side effects 44
Detrol drug-drug interactions 45
Mechanism of action 46
Ditropan (oxybutynin/oxybutynin chloride) 46
Ditropan drug overview 46
Ditropan extended release 48
Forecasts to 2016 49
SWOT analysis 50
Clinical trial data 50
Ditropan's clinical program and study designs 50
Efficacy of Ditropan XL 51
Ditropan XL side effects 51
Oxytrol/Kentera (oxybutynin transdermal patch) 52
Drug overview 52
Forecasts to 2016 54
SWOT analysis 55
Clinical trial data 55
Oxytrol clinical program and study designs 55
Efficacy of Oxytrol 55
Side effects of Oxytrol 56
Mechanism of action 56
Sanctura (trospium chloride) 57
Drug overview 57
Forecasts to 2016 58
Clinical trial data 60
Sanctura clinical program and study designs 60
Efficacy of Sanctura 60
Side effects of Sanctura 60
Mechanism of action 61
Vesicare (solifenacin succinate) 61
Drug overview 61
Forecasts to 2016 64
SWOT analysis 65
Clinical trial data 65
Vesicare's clinical trial program and study designs 65
Efficacy of Vesicare 66
Side effects of Vesicare 66
Mechanism of action 67
Enablex (Darifenacin) 67
Drug overview 67
Forecasts to 2016 69
SWOT analysis 70
Clinical trial data 70
Enablex's clinical trial program and study designs 70
Efficacy of Enablex 71
Side effects of Enablex 71
Yentreve (duloxetine) 71
Drug overview 71
Forecasts to 2016 74
Clinical trial data 74
Efficacy and side effect profile observed in clinical trial program 75
Mictonorm/Detrunorm/BUP-4 (propiverine) 78
Drug overview 78
Forecasts to 2016 79
Clinical trial data 80
Efficacy 80
Side-effect profile 80
Drug-drug interactions 80
Hormone therapy (Estradiol) 81
Others 82
CHAPTER 4 FORECAST ANALYSIS 83
Key events 84
New product launches 85
Key drug launch assumptions 85
Product launches in Japan 86
Darifenacin (Enablex) 86
Imidafenacin (ONO-8025) (KRP-197) (Staybla/Uritos) 86
Reformulations 87
Detrol LA, Toviaz 87
Sanctura, Sanctura XR 87
Oxybutynin 88
Patent expiries 88
Sanctura 88
Detrol LA 89
Yentreve 89
Raft of patent expires in 2015 89
Data definitions, limitations and assumptions 89
Standard units 89
Japanese market data 89
Derivation of sales forecasts and pricing trends 90
Forecast methodology 90
CHAPTER 5 GLOBAL OPPORTUNITIES AND THREATS 91
Key opportunities 92
Stress urinary incontinence 92
Room for a non-anticholinergic treatment 93
Niche topical market 93
Increased awareness 94
Elderly population 94
Key threats 95
Generic anticholinergics 95
Behavioral/surgical techniques 96
Anticholinergic brands dominant 96
CHAPTER 6 PIPELINE OVERVIEW - R&D DYNAMICS AND APPROACH 97
Pipeline overview 98
Classification of pipeline products 98
Cholinergics 98
Adrenergic drugs 99
NK-1 modulators 99
Other drug classes 99
Clinical trial design 100
Clinical trial endpoints in UI 100
Subjective outcome measures 100
Quantification of symptoms 100
Diaries 100
Pad weighing tests 102
Quality of life 102
Choice of endpoints 102
Specific safety aspects 103
CHAPTER 7 LATE-STAGE DRUG ANALYSIS & FORECASTS 104
Late-stage pipeline overview 105
Cholinergic class pipeline drugs 107
Pipeline summary 107
Sanctura XR 108
Drug overview 108
Forecasts to 2016 109
Marketing factors 111
Patient potential 111
Satisfaction of unmet needs 112
Clinical trial data 113
Toviaz (fesoterodine) 114
Drug overview 114
Forecasts to 2016 115
Marketing factors 117
Patient potential 118
Satisfaction of unmet needs 118
Clinical trial data 119
Oxybutynin transdermal gel 121
Drug overview 121
Antares Pharma's oxybutynin gel 122
Watson Pharmaceuticals' oxybutynin gel 122
Forecasts to 2016 123
Marketing factors 126
Patient potential 127
Satisfaction of unmet needs 127
Oxybutynin TVR 128
Botox 129
Drug overview 129
Forecasts to 2016 130
Marketing factors 132
Patient potential 133
Satisfaction of unmet needs 133
Clinical trial data 135
SVT-40776 136
Adrenergic class pipeline drugs 137
Pipeline summary 138
YM-178 138
Drug overview: 138
Forecasts to 2016 139
Clinical trial data 139
PSD-503 139
MN-246 141
NK-1 modulator class pipeline drugs 142
Pipeline summary 142
NK-1 antagonist-theoretical clinical profile and forecast 142
Forecasts to 2016 144
Patient potential 144
Satisfaction of unmet needs 145
Casopitant (Rezonic) 146
SSR-240600 146
TA-5538 146
Other pipeline drugs 147
Pipeline summary 147
VD3 analog (Elocalcitol) 147
Drug overview 147
Forecasts to 2016 148
Marketing factors 150
Patient potential 150
Unmet needs 150
Clinical trial data 151
RCD-1 152
FP-1097 152
URG-101 152
MK-0634 153
FE-106483 153
F-2695 153
Recently suspended/discontinued drugs 153
Cizolirtine 153
(+)-(S,S) Reboxetine 154
REC-0545 155
Saredutant 155
KW-7158 155
KUC-7483 155
CHAPTER 8 EARLY-STAGE PROJECTS 156
Key Phase I and earlier compounds in development for UI 157
Phase I overview 157
Stem cell therapy for SUI 159
Vanilloid agents 159
BIBLIOGRAPHY 161
Journal papers 161
Websites 163
DM reports 168
APPENDIX 169
Report methodology 169
Contributing experts 171
About Datamonitor 171
About Datamonitor Healthcare 171
About the Women's Health and Urology analysis team 172
Disclaimer 174
List of Tables
Table 1: Definitions of UUI, SUI and MUI, according to the ICS 11
Table 2: Prevalence of UI across the seven major markets, 2007 14
Table 3: Detrol/Detrol LA: key facts 37
Table 4: Confidence intervals for the difference between Detrol and placebo 41
Table 5: Confidence intervals for the difference between Detrol LA and placebo 44
Table 6: Ditropan/Ditropan XL: key facts 47
Table 7: Oxytrol: key facts 53
Table 8: Sanctura: key facts 58
Table 9: Vesicare: key facts 63
Table 10: Enablex: key facts 68
Table 11: Yentreve: key facts 73
Table 12: Forecast launch dates in the US and 5EU 85
Table 13: Forecast launch dates in Japan 86
Table 14: Pivotal patent expiries for key marketed drugs in the US and 5EU 88
Table 15: Key pipeline drugs in late-stage development for UI, 2007 106
Table 16: Key late-stage development pipeline, cholinergic class, 2007 107
Table 17: Key factors impacting sales of Sanctura XR, 2007-16 110
Table 18: Key factors impacting sales of Toviaz, 2007-16 116
Table 19: Key factors impacting sales of oxybutynin gel, 2007-16 125
Table 20: Key factors impacting sales of Botox, 2007-16 131
Table 21: Key late-stage development pipeline, adrenergic class, 2007 138
Table 22: Key late-stage development pipeline, NK-1 modulator class, 2007 142
Table 23: Key late-stage development pipeline, other classes, 2007 147
Table 24: Key factors impacting sales of Elocalcitol, 2007-16 149
Table 25: Projects in Phase I and Preclinical development for UI, 2007 157
Table 26: Datamonitor drug assessment parameters 170
List of Figures
Figure 1: Drug assessment summary overview of key marketed and pipeline urinary incontinence drugs, 2007 6
Figure 2: Historical (2003-06) and forecast (2007-16) UI sales revenue for key marketed and pipeline drugs across the 7MM 7
Figure 3: Relationship between UI and OAB 12
Figure 4: Female population suffering from each OAB/UI subtype 15
Figure 5: Female UI/OAB patients according to age group, across the seven major markets 16
Figure 6: Risks of specific side effects, according to interviewed physicians 20
Figure 7: UI-specific sales revenue, 7MM, 2003-06 28
Figure 8: UI-specific sales by revenue, by region and country, 2006 29
Figure 9: UI-specific sales by standard unit, by region and country, 2006 30
Figure 10: UI total market value in the US, Japan and 5EU, 2003-16 31
Figure 11: Current marketed drugs-clinical and commercial assessment 34
Figure 12: Sales (2006) and sales growth (2005-06) for key UI products 35
Figure 13: Detrol LA UI-specific sales revenue, 7MM, 2003-16 38
Figure 14: Detrol LA SWOT analysis 39
Figure 15: Ditropan XL UI-specific sales revenue, 7MM, 2003-16 49
Figure 16: Ditropan XL SWOT analysis 50
Figure 17: Oxytrol UI-specific sales revenue, 7MM, 2003-16 54
Figure 18: Oxytrol SWOT analysis 55
Figure 19: Sanctura UI-specific sales revenue, 7MM, 2003-16 58
Figure 20: Vesicare UI-specific sales revenue, 7MM, 2003-16 64
Figure 21: Vesicare SWOT analysis 65
Figure 22: Enablex UI-specific sales revenue, 7MM, 2003-16 69
Figure 23: Enablex SWOT analysis 70
Figure 24: Yentreve UI-specific sales revenue, 7MM, 2003-16 74
Figure 25: Mictonorm UI-specific sales revenue, 7MM, 2003-16 79
Figure 26: Impact of each key event on the UI market across the seven major markets, 2007-2016 84
Figure 27: SUI most prevalent indication 92
Figure 28: Generic UI sales, 7MM, 2003-16 95
Figure 29: Drugs in late-stage development by class, 2007+ 98
Figure 30: Key late-stage pipeline overview, 2007 105
Figure 31: Forecast UI sales for Sanctura XR 7MM, 2007-16 109
Figure 32: Drug assessment summary for Sanctura XR, 2007 110
Figure 33: Forecast UI sales for Toviaz, 7MM, 2007-16 115
Figure 34: Drug assessment summary for Toviaz, 2007 117
Figure 35: Forecast UI sales for oxybutynin gel 7MM, 2007-16 123
Figure 36: Drug assessment summary for Oxybutynin gel, 2007 126
Figure 37: Forecast UI sales for Botox, 7MM, 2007-16 130
Figure 38: Drug assessment summary for Botox, 2007 132
Figure 39: Forecast UI sales for an NK-1 antagonist 7MM, 2007-16 144
Figure 40: Forecast UI sales for Elocalcitol 7MM, 2007-16 148
Figure 41: Drug assessment summary for Elocalcitol, 2007 149