Pipeline and Commercial Insight: Alzheimer's Disease - Scenario forecasts reveal vast market potential

CHAPTER 1 EXECUTIVE SUMMARY 3
Scope of the analysis 3
Contributing experts 3
Datamonitor insight into the Alzheimer's disease market 5
Scenario forecasts - a pivotal point in the Alzheimer's disease market 7
Base scenario 8
Total market forecast 8
Drug forecasts 9
Key pipeline drug assessment 10
Related reports 11

CHAPTER 2 MARKET OVERVIEW AND POTENTIAL 13
Market and disease definition 14
Definition of Alzheimer's disease market 14
Current market value 15
5- year AD market size 15
Growth stimulated by Namenda uptake 15
The US has dominated sales over the last 5 years 16
Drug sales split by AD and non-AD indications 17
Percentage of AChEIs and Namenda sales attributed to AD 18
Total all-indication sales of AChEIs and Namenda 19
Market forecasts 20
Four possible future market scenarios are presented 20
1. Base scenario 20
2. No bapineuzumab scenario 21
3. No potentially disease slowing therapy (PDST) scenario 22
4. High US prevalence scenario 23
Epidemiology of Alzheimer's disease 24
Prevalence 24
Datamonitor's AD epidemiology methodology 25
Comparison with other reported AD prevalence rates in the US 27
Diagnosis and presentation rate 29
Unmet need in AD 30
Disease modifying/slowing treatments 30
Improved symptomatic efficacy 33
Better diagnostic tools 34
Disease subtype targeted therapy 35
Etiology of AD 35
Beta-amyloid hypothesis 35
Tau neurofibrillary tangles 38
Neuronal death caused by beta-amyloid deposition and neurofibrillary tangles formation 38
Diagnosis and treatment options 39
Diagnosis techniques 39
Diagnosis still poses a large challenge but there is hope on the horizon 39
Diagnostic guidelines for AD are provided by multiple sources 40
Severity of AD is often assessed using symptomatic subscales 41
A holistic view of AD progression is lacking 42
Drug classes used to treat AD 42
Acetylcholinesterase inhibitors 42
NMDA receptor antagonist: memantine (Namenda/Ebixa/Axura) 44

CHAPTER 3 BRAND DYNAMICS AND LEADING COMPARATOR THERAPIES 45
Marketed brands overview 46
Historical and forecasted sales of current marketed brands and reformulations 46
Aricept (donepezil) - Current gold standard AD treatment 47
Drug overview 47
Forecast 47
Drug assessment 49
SWOT analysis 50
Clinical trial data 50
12-week study 51
24-week study 51
Aricept SR 52
Drug overview 52
Datamonitor comments 52
Razadyne (galantamine) 53
Drug overview 53
Forecast 55
SWOT analysis 56
Oral Exelon and Exelon patch (rivastigmine) 56
Drug overview 56
Forecast 59
SWOT analysis 60
Namenda (memantine) 61
Drug overview 61
Forecast 62
SWOT analysis 63
Once daily Namenda reformulation 63

CHAPTER 4 FORECAST ANALYSIS 67
Key events 68
New product launches and reformulations 68
Patent expiries 69
Aricept (donepezil) 69
Razadyne (galantamine) 69
Exelon (rivastigmine) 70
Namenda (memantine) 70
Data definitions, limitations and assumptions 71
Standard units 71
Japanese market data 71
Derivation of sales forecasts and pricing trends 71
Forecast methodology 71

CHAPTER 5 GLOBAL OPPORTUNITIES AND THREATS 72
Overview 73
Key opportunities 73
Ageing population 73
Changing population demographic - ageing population 73
AD patient population grows dramatically as the general population ages 75
Poor current therapies leave room for new market entrants 76
Improved diagnostic tools facilitate indication expansions and improve treatment rates 78
Key threats 80
Unproven neurodegenerative pathway introduces high risk 80
Generic incursion 82

CHAPTER 6 PIPELINE OVERVIEW - R&D DYNAMICS AND APPROACH 84
Late-stage pipeline overview 85
Revenue potential of three key drugs 85
Clear movement towards disease modification in the late-stage pipeline 85
Clinical trial endpoints 89
Alzheimer's Disease Assessment Scale-cognitive portion (ADAS-Cog) 91
Neuropsychological Test Battery (NTB) 91
Mini-Mental Status Exam (MMSE) 92
Clinician's Interview-Based Impression of Change 92
Severe Impairment Battery 93
Alzheimer's Disease Cooperative Study: Activities of Daily Living (ADCS-ADL) 93
Neuropsychiatric Inventory 93
Clinical Dementia Rating 94

CHAPTER 7 POTENTIALLY DISEASE SLOWING THERAPIES - LATE-STAGE DRUG ANALYSIS & FORECASTS 95
Beta-amyloid modulating drug class 96
Flurizan (tarenflurbil) 96
Drug overview 96
Forecasts to 2017 98
Marketing factors 105
Patient potential 111
Satisfaction of unmet needs 112
Clinical trial data 112
Ongoing clinical trial program 113
Bapineuzumab (AAB-001) 116
Drug overview 116
Forecasts to 2017 118
Marketing factors 123
Patient potential 130
Satisfaction of unmet needs 132
Clinical trial data and mode of action 132
Ongoing clinical trial program 139
PBT-2 140
Drug overview 140
Clinical trial data 141
Ongoing clinical trial program 144
Other beta-amyloid modulating drugs 144
ACC-001 - immunization 144
PF-4360365- immunization 145
LY2062430- immunization 145
NIC5-15 - beta-amyloid modulation 146
ELND005 (AZD-103) - beta-amyloid modulation 147
LY450139 - beta-amyloid modulation 147
Drugs targeting alternative potentially disease modifying modes of action 149
Dimebon 149
Drug overview 149
Forecasts to 2017 151
Marketing factors 158
Patient potential 160
Satisfaction of unmet needs 162
Clinical trial data 162
Ongoing clinical trials program 165
Rosiglitazone XR 165
Clinical trial data 166
Ongoing clinical trial program 166
Memryte 168
Drug overview 168
Clinical trial data 168
PRX-03140 169
Drug overview 169
Clinical trial data - Phase IIa clinical trial 169
Cogane 170
Drug overview 170
Clinical trial data 170
Other drugs targeting disease modifying modes of action 172
Ketasyn 172
AL-108 172
HF0220 173
Azilect (rasagiline) 174
Ampakine (CX717) 174
MND-21 174
Cereact (ONO-2506PO) 175
PF-4494700 (TTP488) 175
Recently discontinued products 176
Alzhemed 176
Drug overview 176
Phase III trial results 176
The future for Alzhemed, a nutraceutical 177

CHAPTER 8 SYMPTOMATIC TREATMENTS - LATE-STAGE DRUG ANALYSIS & FORECASTS 178
Acetylcholinesterase Inhibitors (AChEIs) 179
Huperzine A 179
Drug overview 179
Clinical trial data 180
Ongoing clinical trial program 182
Debio 9902 182
Drug overview 182
Ongoing clinical trial program 183
NMDA receptor antagonists 183
Neramexane 183
Drugs targeting alternative symptomatic modes of action 184
MEM 3454 184
Drug overview 184
Clinical trial data 184
Other drugs targeting alternative symptomatic modes of action 185
AZD3480 (ispronicline, TC-1734) 185
MK-0249 186
AC-3933 186
Lecozotan 187

BIBLIOGRAPHY 189
Journals 189
Websites 196
Datamonitor Reports 208
APPENDIX 209
Report methodology 209
Contributing experts 210
About Datamonitor 211
About Datamonitor Healthcare 211
About the CNS analysis team 212
Disclaimer 213

List of Tables
Table 1: Percentage of total drugs sales for AD, 2003-07 18
Table 2: Population size and prevalence rate of AD across the 7MM, 2008 25
Table 3: Prevalence of Alzheimer's disease by gender and age, 2008 27
Table 4: DSM-IV criteria for Alzheimer's disease type dementia 41
Table 5: Forecast launch dates in the US, 5EU and Japan 68
Table 6: Patent expiry dates for Aricept, 2010-12 69
Table 7: Patent expiry dates for Razadyne, 2008-2012 69
Table 8: Patent expiry dates for Exelon, 2011-12 70
Table 9: Patent expiry dates for Namenda, 2010-14 70
Table 10: Summary of key opportunities and threats to the future AD market 73
Table 11: Comparison of AChEI treatment response outcomes, according to a meta-analysis of clinical trials, 2008 77
Table 12: Key potentially disease slowing/modifying pipeline drugs in late-stage development for AD, 2008 87
Table 13: Key symptomatic pipeline drugs in late-stage development for AD, 2008 89
Table 14: Measures used for clinical efficacy endpoints in AD 90
Table 15: Flurizan base scenario forecast ($m), US, 2017 99
Table 16: Flurizan base scenario forecast ($m), 5EU, 2017 100
Table 17: Flurizan base scenario forecast ($m), Japan, 2017 101
Table 18: Key events for Flurizan, 2008-2017 102
Table 19: US sales revenue ($m) scenario matrix for Flurizan 103
Table 20: 5EU sales revenue ($m) scenario matrix for Flurizan 103
Table 21: Japan sales revenue ($m) scenario matrix for Flurizan 104
Table 22: Bapineuzumab base scenario forecast ($m), US, 2017 119
Table 23: Bapineuzumab base scenario forecast ($m), 5EU, 2017 119
Table 24: Bapineuzumab base scenario forecast ($m), Japan, 2017 120
Table 25: Key events for bapineuzumab, 2008-2017 120
Table 26: US sales revenue ($m) scenario matrix for bapineuzumab 121
Table 27: 5EU sales revenue ($m) scenario matrix for bapineuzumab 122
Table 28: Japan sales revenue ($m) scenario matrix for bapineuzumab 122
Table 29: Cost of other mAbs (or mAb-related fusion proteins) in the US 124
Table 30: Cost-benefit analysis of bapineuzumab, 7MM 126
Table 31: Savings following patent expiry of symptomatic treatments for AD, US 128
Table 32: Key events for Dimebon, 2008-2017 152
Table 33: Dimebon base scenario forecast ($m), US, 2017 153
Table 34: Dimebon base scenario forecast ($m), 5EU, 2017 154
Table 35: Bapineuzumab base scenario forecast ($m), Japan, 2017 155
Table 36: US sales revenue ($m) scenario matrix for Dimebon 156
Table 37: 5EU sales revenue ($m) scenario matrix for Dimebon 156
Table 38: Japan sales revenue ($m) scenario matrix for Dimebon 157
Table 39: Datamonitor drug assessment parameters for AD market 210

List of Figures
Figure 1: Base scenario - historical and forecast total AD market, 2004-2017 8
Figure 2: Historical (2006-07) and forecast (2008-17) AD sales revenue for key marketed and pipeline drugs across the 7MM 9
Figure 3: Drug assessment summary overview of key marketed and pipeline Alzheimer's disease drugs, 2008 10