Pipeline and Commercial Insight: Alzheimer's Disease
Scope
Report Highlights
Reasons to Purchase
Table of Contents
- ABOUT DATAMONITOR HEALTHCARE - page 2
- About the Central Nervous System pharmaceutical analysis team - page 2
- CHAPTER 1 EXECUTIVE SUMMARY - page 3
- Scope of the analysis - page 3
- Contributing experts - page 3
- Datamonitor insight into the Alzheimer\'s disease market - page 5
- Scenario forecasts - a pivotal point in the Alzheimer\'s disease market - page 7
- Base scenario - page 8
- Total market forecast - page 8
- Drug forecasts - page 9
- Key pipeline drug assessment - page 10
- Related reports - page 11
- CHAPTER 2 MARKET OVERVIEW AND POTENTIAL - page 13
- Market and disease definition - page 14
- Definition of Alzheimer\'s disease market - page 14
- Current market value - page 15
- 5- year AD market size - page 15
- Growth stimulated by Namenda uptake - page 15
- The US has dominated sales over the last 5 years - page 16
- Drug sales split by AD and non-AD indications - page 17
- Percentage of AChEIs and Namenda sales attributed to AD - page 18
- Total all-indication sales of AChEIs and Namenda - page 19
- 5- year AD market size - page 15
- Market forecasts - page 20
- Four possible future market scenarios are presented - page 20
- 1. Base scenario - page 20
- 2. No bapineuzumab scenario - page 21
- 3. No potentially disease slowing therapy (PDST) scenario - page 22
- 4. High US prevalence scenario - page 23
- Four possible future market scenarios are presented - page 20
- Epidemiology of Alzheimer\'s disease - page 24
- Prevalence - page 24
- Datamonitor\'s AD epidemiology methodology - page 25
- Comparison with other reported AD prevalence rates in the US - page 27
- Diagnosis and presentation rate - page 29
- Prevalence - page 24
- Unmet need in AD - page 30
- Disease modifying/slowing treatments - page 30
- Improved symptomatic efficacy - page 33
- Better diagnostic tools - page 34
- Disease subtype targeted therapy - page 35
- Etiology of AD - page 35
- Beta-amyloid hypothesis - page 35
- Tau neurofibrillary tangles - page 38
- Neuronal death caused by beta-amyloid deposition and neurofibrillary tangles formation - page 38
- Diagnosis and treatment options - page 39
- Diagnosis techniques - page 39
- Diagnosis still poses a large challenge but there is hope on the horizon - page 39
- Diagnostic guidelines for AD are provided by multiple sources - page 40
- Severity of AD is often assessed using symptomatic subscales - page 41
- A holistic view of AD progression is lacking - page 42
- Diagnosis techniques - page 39
- Drug classes used to treat AD - page 42
- Acetylcholinesterase inhibitors - page 42
- NMDA receptor antagonist: memantine (Namenda/Ebixa/Axura) - page 44
- Market and disease definition - page 14
- CHAPTER 3 BRAND DYNAMICS AND LEADING COMPARATOR THERAPIES - page 45
- Marketed brands overview - page 46
- Historical and forecasted sales of current marketed brands and reformulations - page 46
- Aricept (donepezil) - Current gold standard AD treatment - page 47
- Drug overview - page 47
- Forecast - page 47
- Drug assessment - page 49
- SWOT analysis - page 50
- Clinical trial data - page 50
- 12-week study - page 51
- 24-week study - page 51
- Aricept SR - page 52
- Drug overview - page 52
- Datamonitor comments - page 52
- Razadyne (galantamine) - page 53
- Drug overview - page 53
- Forecast - page 55
- SWOT analysis - page 56
- Oral Exelon and Exelon patch (rivastigmine) - page 56
- Drug overview - page 56
- Forecast - page 59
- SWOT analysis - page 60
- Namenda (memantine) - page 61
- Drug overview - page 61
- Forecast - page 62
- SWOT analysis - page 63
- Once daily Namenda reformulation - page 63
- Marketed brands overview - page 46
- CHAPTER 4 FORECAST ANALYSIS - page 67
- Key events - page 68
- New product launches and reformulations - page 68
- Patent expiries - page 69
- Aricept (donepezil) - page 69
- Razadyne (galantamine) - page 69
- Exelon (rivastigmine) - page 70
- Namenda (memantine) - page 70
- Data definitions, limitations and assumptions - page 71
- Standard units - page 71
- Japanese market data - page 71
- Derivation of sales forecasts and pricing trends - page 71
- Forecast methodology - page 71
- Key events - page 68
- CHAPTER 5 GLOBAL OPPORTUNITIES AND THREATS - page 72
- Overview - page 73
- Key opportunities - page 73
- Ageing population - page 73
- Changing population demographic - ageing population - page 73
- AD patient population grows dramatically as the general population ages - page 75
- Poor current therapies leave room for new market entrants - page 76
- Improved diagnostic tools facilitate indication expansions and improve treatment rates - page 78
- Ageing population - page 73
- Key threats - page 80
- Unproven neurodegenerative pathway introduces high risk - page 80
- Generic incursion - page 82
- CHAPTER 6 PIPELINE OVERVIEW - R&D DYNAMICS AND APPROACH - page 84
- Late-stage pipeline overview - page 85
- Revenue potential of three key drugs - page 85
- Clear movement towards disease modification in the late-stage pipeline - page 85
- Clinical trial endpoints - page 89
- Alzheimer\'s Disease Assessment Scale-cognitive portion (ADAS-Cog) - page 91
- Neuropsychological Test Battery (NTB) - page 91
- Mini-Mental Status Exam (MMSE) - page 92
- Clinician\'s Interview-Based Impression of Change - page 92
- Severe Impairment Battery - page 93
- Alzheimer\'s Disease Cooperative Study: Activities of Daily Living (ADCS-ADL) - page 93
- Neuropsychiatric Inventory - page 93
- Clinical Dementia Rating - page 94
- Late-stage pipeline overview - page 85
- CHAPTER 7 POTENTIALLY DISEASE SLOWING THERAPIES - LATE-STAGE DRUG ANALYSIS & FORECASTS - page 95
- Beta-amyloid modulating drug class - page 96
- Flurizan (tarenflurbil) - page 96
- Drug overview - page 96
- Forecasts to 2017 - page 98
- Marketing factors - page 105
- Patient potential - page 111
- Satisfaction of unmet needs - page 112
- Clinical trial data - page 112
- Ongoing clinical trial program - page 113
- Bapineuzumab (AAB-001) - page 116
- Drug overview - page 116
- Forecasts to 2017 - page 118
- Marketing factors - page 123
- Patient potential - page 130
- Satisfaction of unmet needs - page 132
- Clinical trial data and mode of action - page 132
- Ongoing clinical trial program - page 139
- PBT-2 - page 140
- Drug overview - page 140
- Clinical trial data - page 141
- Ongoing clinical trial program - page 144
- Other beta-amyloid modulating drugs - page 144
- ACC-001 - immunization - page 144
- PF-4360365- immunization - page 145
- LY2062430- immunization - page 145
- NIC5-15 - beta-amyloid modulation - page 146
- ELND005 (AZD-103) - beta-amyloid modulation - page 147
- LY450139 - beta-amyloid modulation - page 147
- Flurizan (tarenflurbil) - page 96
- Drugs targeting alternative potentially disease modifying modes of action - page 149
- Dimebon - page 149
- Drug overview - page 149
- Forecasts to 2017 - page 151
- Marketing factors - page 158
- Patient potential - page 160
- Satisfaction of unmet needs - page 162
- Clinical trial data - page 162
- Ongoing clinical trials program - page 165
- Rosiglitazone XR - page 165
- Clinical trial data - page 166
- Ongoing clinical trial program - page 166
- Memryte - page 168
- Drug overview - page 168
- Clinical trial data - page 168
- PRX-03140 - page 169
- Drug overview - page 169
- Clinical trial data - Phase IIa clinical trial - page 169
- Cogane - page 170
- Drug overview - page 170
- Clinical trial data - page 170
- Other drugs targeting disease modifying modes of action - page 172
- Ketasyn - page 172
- AL-108 - page 172
- HF0220 - page 173
- Azilect (rasagiline) - page 174
- Ampakine (CX717) - page 174
- MND-21 - page 174
- Cereact (ONO-2506PO) - page 175
- PF-4494700 (TTP488) - page 175
- Dimebon - page 149
- Recently discontinued products - page 176
- Alzhemed - page 176
- Drug overview - page 176
- Phase III trial results - page 176
- The future for Alzhemed, a nutraceutical - page 177
- Alzhemed - page 176
- Beta-amyloid modulating drug class - page 96
- CHAPTER 8 SYMPTOMATIC TREATMENTS - LATE-STAGE DRUG ANALYSIS & FORECASTS - page 178
- Acetylcholinesterase Inhibitors (AChEIs) - page 179
- Huperzine A - page 179
- Drug overview - page 179
- Clinical trial data - page 180
- Ongoing clinical trial program - page 182
- Debio 9902 - page 182
- Drug overview - page 182
- Ongoing clinical trial program - page 183
- Huperzine A - page 179
- NMDA receptor antagonists - page 183
- Neramexane - page 183
- Drugs targeting alternative symptomatic modes of action - page 184
- MEM 3454 - page 184
- Drug overview - page 184
- Clinical trial data - page 184
- Other drugs targeting alternative symptomatic modes of action - page 185
- AZD3480 (ispronicline, TC-1734) - page 185
- MK-0249 - page 186
- AC-3933 - page 186
- Lecozotan - page 187
- MEM 3454 - page 184
- Acetylcholinesterase Inhibitors (AChEIs) - page 179
- BIBLIOGRAPHY - page 189
- Journals - page 189
- Websites - page 196
- Datamonitor Reports - page 208
- APPENDIX - page 209
- Report methodology - page 209
- Contributing experts - page 210
- About Datamonitor - page 211
- About Datamonitor Healthcare - page 211
- About the CNS analysis team - page 212
- Disclaimer - page 213
- Report methodology - page 209
- List of Tables
- Table 1: Percentage of total drugs sales for AD, 2003-07 - page 18
- Table 2: Population size and prevalence rate of AD across the 7MM, 2008 - page 25
- Table 3: Prevalence of Alzheimer\'s disease by gender and age, 2008 - page 27
- Table 4: DSM-IV criteria for Alzheimer\'s disease type dementia - page 41
- Table 5: Forecast launch dates in the US, 5EU and Japan - page 68
- Table 6: Patent expiry dates for Aricept, 2010-12 - page 69
- Table 7: Patent expiry dates for Razadyne, 2008-2012 - page 69
- Table 8: Patent expiry dates for Exelon, 2011-12 - page 70
- Table 9: Patent expiry dates for Namenda, 2010-14 - page 70
- Table 10: Summary of key opportunities and threats to the future AD market - page 73
- Table 11: Comparison of AChEI treatment response outcomes, according to a meta-analysis of clinical trials, 2008 - page 77
- Table 12: Key potentially disease slowing/modifying pipeline drugs in late-stage development for AD, 2008 - page 87
- Table 13: Key symptomatic pipeline drugs in late-stage development for AD, 2008 - page 89
- Table 14: Measures used for clinical efficacy endpoints in AD - page 90
- Table 15: Flurizan base scenario forecast ($m), US, 2017 - page 99
- Table 16: Flurizan base scenario forecast ($m), 5EU, 2017 - page 100
- Table 17: Flurizan base scenario forecast ($m), Japan, 2017 - page 101
- Table 18: Key events for Flurizan, 2008-2017 - page 102
- Table 19: US sales revenue ($m) scenario matrix for Flurizan - page 103
- Table 20: 5EU sales revenue ($m) scenario matrix for Flurizan - page 103
- Table 21: Japan sales revenue ($m) scenario matrix for Flurizan - page 104
- Table 22: Bapineuzumab base scenario forecast ($m), US, 2017 - page 119
- Table 23: Bapineuzumab base scenario forecast ($m), 5EU, 2017 - page 119
- Table 24: Bapineuzumab base scenario forecast ($m), Japan, 2017 - page 120
- Table 25: Key events for bapineuzumab, 2008-2017 - page 120
- Table 26: US sales revenue ($m) scenario matrix for bapineuzumab - page 121
- Table 27: 5EU sales revenue ($m) scenario matrix for bapineuzumab - page 122
- Table 28: Japan sales revenue ($m) scenario matrix for bapineuzumab - page 122
- Table 29: Cost of other mAbs (or mAb-related fusion proteins) in the US - page 124
- Table 30: Cost-benefit analysis of bapineuzumab, 7MM - page 126
- Table 31: Savings following patent expiry of symptomatic treatments for AD, US - page 128
- Table 32: Key events for Dimebon, 2008-2017 - page 152
- Table 33: Dimebon base scenario forecast ($m), US, 2017 - page 153
- Table 34: Dimebon base scenario forecast ($m), 5EU, 2017 - page 154
- Table 35: Bapineuzumab base scenario forecast ($m), Japan, 2017 - page 155
- Table 36: US sales revenue ($m) scenario matrix for Dimebon - page 156
- Table 37: 5EU sales revenue ($m) scenario matrix for Dimebon - page 156
- Table 38: Japan sales revenue ($m) scenario matrix for Dimebon - page 157
- Table 39: Datamonitor drug assessment parameters for AD market - page 210
- List of Figures
- Figure 1: Base scenario - historical and forecast total AD market, 2004-2017 - page 8
- Figure 2: Historical (2006-07) and forecast (2008-17) AD sales revenue for key marketed and pipeline drugs across the 7MM - page 9
- Figure 3: Drug assessment summary overview of key marketed and pipeline Alzheimer\'s disease drugs, 2008 - page 10
- Figure 4: AD-specific sales revenue, 7MM, 2003-07 - page 16
- Figure 5: AD-specific sales revenue ($ billion) by region, 2004-07 - page 17
- Figure 6: Proportion of drug sales revenue for AD across the 7MM, E2007 - page 18
- Figure 7: Percentage of drug sales for AD across the 7MM, 2003-07 - page 19
- Figure 8: 7MM all indication sales revenue, 2006 and E2007 - page 20
- Figure 9: Base scenario - historical and forecast total AD market, 2004-2017 - page 21
- Figure 10: No bapineuzumab - AD total market forecast, 2004-2017 - page 22
- Figure 11: No PDST - AD total market forecast, 2004-2017 - page 23
- Figure 12: High US prevalence - AD total market forecast, 2004-2017 - page 24
- Figure 13: Overview of Datamonitor\'s AD population size methodology, 2008 - page 26
- Figure 14: Comparison of data from individual AD incidence studies - page 28
- Figure 15: Key unmet needs in AD, 2008 - page 30
- Figure 16: Cognitive decline of untreated AD patients, and patients treated with a symptomatic drug - page 31
- Figure 17: AD symptom progression in the presence of a disease slowing therapy - page 32
- Figure 18: AD symptom progression in the presence of a superior symptomatic drug - page 33
- Figure 19: AD symptom progression in the presence of a disease modifying treatment administered at an early stage of the disease due to better diagnostic tools - page 34
- Figure 20: Amyloidogenic pathway: Formation of toxic beta-amyloid - page 37
- Figure 21: Base scenario: marketed AD drug and reformulation revenue forecasts, 2004-2017 - page 46
- Figure 22: Aricept sales revenue ($m) across the 7MM, 2004-07, 2008-2017 forecasts - page 48
- Figure 23: Drug assessment of the commercial and clinical attractiveness of Aricept, 2008 - page 49
- Figure 24: Aricept SWOT analysis, 2008 - page 50
- Figure 25: Razadyne sales revenue in the US and 5EU ($m), 2004-07 - page 54
- Figure 26: Razadyne/Razadyne SR sales revenue ($m) across the 7MM, 2004-07, 2008-2017 forecasts - page 55
- Figure 27: Razadyne SWOT analysis, 2008 - page 56
- Figure 28: The Exelon Patch - page 58
- Figure 29: Exelon and Exelon patch sales revenue ($m) across the 7MM, 2004-07, 2008-2017 forecasts - page 59
- Figure 30: SWOT analysis of Exelon franchise (i.e. oral and patch), 2008 - page 60
- Figure 31: Namenda and Namenda ER sales revenue ($m) across the 7MM, 2004-07, 2008-2017 forecasts - page 62
- Figure 32: Namenda SWOT analysis, 2008 - page 63
- Figure 33: Impact of each key event on the AD market across the seven major markets, 2008-2017 - page 68
- Figure 34: Population distribution by age across the 7MM, 2005-2045 - page 74
- Figure 35: Ageing population across 7MM, 2005-2050 - page 75
- Figure 36: Forecast AD population, 2005-2050 - page 76
- Figure 37: Impact of generic incursion on 7MM branded drug sales, 2004-2017 - page 83
- Figure 38: Key late-stage pipeline overview in Datamonitor\'s base scenario, 2008-2017 - page 85
- Figure 39: Number of symptomatic and potential disease slowing late-stage pipeline drugs in development for AD, 2008 - page 86
- Figure 40: Forecast Flurizan sales revenue ($m) across the 7MM, 2008-2017 - page 98
- Figure 41: Drug assessment of the commercial and clinical attractiveness of Flurizan, 2008 - page 105
- Figure 42: Cognitive status of an AD patient - page 109
- Figure 43: Randomized withdrawal trial design - page 115
- Figure 44: Staggered start trial design - page 116
- Figure 45: Bapineuzumab sales revenue ($m), 2008-2017 - page 118
- Figure 46: Drug assessment of the commercial and clinical attractiveness of bapineuzumab, 2008 - page 123
- Figure 47: Equilibrium of beta-amyloid in the brain and the rest of the body - page 138
- Figure 48: The effect of bapineuzumab on distribution of beta-amyloid - page 138
- Figure 49: Dimebon sales revenue ($m), 2008-2017 - page 151
- Figure 50: Drug assessment of the commercial and clinical attractiveness of Dimebon, 2008 - page 157
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