Pipeline and Commercial Insight: Alzheimer’s Disease
Scope
Report Highlights
Reasons to Purchase
Table of Contents
- ABOUT DATAMONITOR HEALTHCARE - page 2
- About the CNS pharmaceutical analysis team - page 2
- CHAPTER 1 EXECUTIVE SUMMARY - page 3
- Objective of the analysis - page 3
- Datamonitor insight into the AD market - page 3
- Key opinion leaders - page 5
- Key metrics - page 6
- CHAPTER 2 PATIENT POTENTIAL - page 25
- Definition of Alzheimer's disease - page 25
- Segmentation of Alzheimer's disease - page 26
- Mild AD affects memory, language and reasoning - page 26
- Moderate AD demonstrates more pronounced symptoms - page 27
- Severe AD leaves patients completely dependent - page 27
- Mild cognitive impairment (MCI) may be a precursor to AD - page 30
- Comorbidities or symptoms? - page 30
- Treatments for comorbidities - page 31
- Treating depression improves quality of life and behavior - page 31
- Treatment of agitation, aggression and psychotic symptoms is limited by side effects - page 31
- Anxiety is treated using antidepressants and benzodiazepines - page 32
- Treatment of sleep disturbances is a difficult balance of sedation - page 33
- Broad symptomatology provides commercial opportunity - page 33
- Treatments for comorbidities - page 31
- Diagnosis of Alzheimer's disease is generally by exclusion - page 36
- Diagnostic guidelines for AD are provided by multiple sources - page 36
- Severity of AD is often assessed using symptomatic subscales - page 37
- An holistic view of AD progression is lacking - page 38
- Diagnosis and treatment rates restrict commercial potential - page 38
- Diagnostic guidelines for AD are provided by multiple sources - page 36
- Epidemiology of Alzheimer's disease - page 40
- CHAPTER 3 MARKET OVERVIEW - page 45
- Market definition for this report - page 45
- The current AD market - page 45
- The major AD market players and franchises - page 48
- Acetylcholinesterase Inhibitors (AChEIs) dominate the market - page 48
- Pfizer/Eisai's Aricept (donepezil) - page 49
- J&J's Razadyne (galantamine) franchise - page 50
- Novartis's Exelon (rivastigmine) - page 52
- NMDA receptor antagonists - page 52
- Forest's Namenda (memantine) - page 53
- The major AD market players and franchises - page 48
- Unmet needs in Alzheimer's disease - page 54
- Disease modification - page 56
- Improved efficacy - page 56
- Fewer side effects - page 56
- Reducing numbers of treatment unresponsive patients - page 57
- Patient compliance - page 57
- CHAPTER 4 COUNTRY MARKET ASSESSMENT - page 58
- Global opportunities and threats - page 58
- Opportunities - page 58
- Demographics will continue to expand the market size - page 58
- Increased use of combination therapy as the disease progresses - page 58
- Clinical unmet needs ensure pipeline drugs will drive future growth - page 59
- Improvements in diagnosis will increase treatment rates - page 60
- New EU legislation will increase data exclusivity period, providing increased return on investment for new products - page 60
- Efficacy in other indications could expand the market - page 61
- Threats - page 61
- Introduction of generic competitors will increase focus on cost - page 61
- The economic cost of geriatric healthcare puts drugs without clear benefits at risk - page 61
- Parallel imports; EU expansion is likely to drive down price - page 62
- Opportunities - page 58
- US - page 62
- Market overview - page 62
- Opportunities - page 66
- High public awareness driven by advocacy & DTC campaigns - page 66
- Direct access to specialist physicians helps patients receive optimal treatment quicker - page 67
- Threats - page 67
- Generic entrants increase competition and impact price - page 67
- Although providing drug benefit for the elderly, the future implications of the Medicare Modernization Act (MMA) are uncertain - page 68
- FDA self-regulation will lead to stricter safety evaluations - page 70
- Japan - page 70
- Market overview - page 70
- Opportunities - page 72
- Under-developed market with room for expansion - page 72
- Improvements in diagnosis and increased awareness would increase drug sales - page 72
- Pricing process slows generic incursion - page 73
- Separation of manufacturing and marketing entities opens market to overseas companies - page 73
- Faster product approval accelerates the time to market - page 74
- Threats - page 74
- Biennial price cuts restrict profit - page 74
- Healthcare reforms focus on severe reductions in pharmaceutical expenditure - page 75
- Genericization is slowly taking off - page 76
- France - page 77
- Market overview - page 77
- Opportunities - page 80
- Approval in other AD subgroups would improve the target patient pool - page 80
- Innovative drug development encouraged by price premium and high-level reimbursement - page 80
- Threats - page 80
- Healthcare reforms limit patient access to specialists - page 80
- Price reductions restrict return on investment - page 81
- Re-evaluation of cost-effectiveness and safety data threatens reimbursement status - page 82
- Drives to promote generic substitution - page 82
- Germany - page 83
- Market overview - page 83
- Opportunities - page 85
- Promotion and education could realize the EU's greatest patient potential - page 85
- Loophole in 2004 reform exploited for price increases - page 86
- ePharmacy and mail-order legalization increases access to drugs and information - page 87
- Threats - page 88
- Focus on prescriber overspend in addition to patient co-payments support lower-priced therapies - page 88
- Italy - page 89
- Market overview - page 89
- Opportunities - page 92
- Low treatment rates suggest scope for expansion - page 92
- Innovative drug development rewarded with premium price and 100% reimbursement - page 92
- UVAs increasing AD treatment efforts - page 93
- Threats - page 94
- Legislation enforces cost-containment in a market already characterized by low pricing - page 94
- Pricing can disqualify products from reimbursement - page 95
- Spain - page 96
- Market overview - page 96
- Opportunities - page 98
- Drive to improve Alzheimer's care - page 98
- Regional differences provide localized opportunities - page 99
- Drug innovation encouraged by enhanced financing - page 99
- Threats - page 100
- Regulatory and financial barriers to reimbursement - page 100
- A complex pricing system compounded by regular changes and regional variation is a barrier to usual pricing strategies - page 100
- Generic penetration still low but expected to increase - page 101
- UK - page 102
- Market overview - page 102
- Opportunities - page 105
- Severe AD may offer an undertreated population - page 105
- Threats - page 105
- NICE guidance threatens the reimbursement status of AD drugs - page 105
- Health Select Committee report clamps down on pharmaceutical promotion - page 106
- Pharmaceutical Price Regulation Scheme (PPRS) curbs price increases - page 108
- Cost-containment measures encourage continued high use of generics - page 108
- The UK is the top importer for parallel trade - page 109
- Global opportunities and threats - page 58
- CHAPTER 5 R&D APPROACH - page 110
- Classification of pipeline products - page 110
- ACh modulators are the foundation of current treatment - page 111
- NMDA receptor antagonists lead the way in moderate to severe AD - page 112
- Neuroprotective and neurotrophic drugs are developing from a variety of approaches - page 113
- Beta-amyloid modulators reduce plaque deposition - page 114
- Other compounds in development - page 114
- Statins - the potential in AD is still unclear - page 114
- Anti-inflammatory drugs - future hampered by safety concerns - page 115
- Antioxidants may reduce cell death - page 116
- Insulin's role in AD is being defined - page 116
- Clinical trial characteristics in Alzheimer's disease - page 117
- Gold standard - page 117
- Patient population should be assessed for severity and potential responders - page 118
- Trial duration must reflect chronic nature of AD - page 120
- Trial endpoints should include more than cognitive function - page 121
- Measurement scales in Alzheimer's disease - page 122
- Alzheimer's disease assessment scale (ADAS) - page 124
- Mini-Mental Status Exam - page 124
- Clinician's Interview-Based Impression of Change - page 125
- Severe Impairment Battery - page 125
- Alzheimer's Disease Cooperative Study: Activities of Daily Living - page 125
- Neuropsychiatic Inventory - page 126
- Clinical Dementia Rating - page 126
- Classification of pipeline products - page 110
- CHAPTER 6 DRUG PIPELINE ANALYSIS - page 127
- Pipeline overview - page 127
- Phase III overview - page 128
- Phase II overview - page 131
- Phase I overview - page 133
- Key companies involved in the AD pipeline - page 134
- Eli Lilly - page 135
- Sanofi-Aventis - page 136
- Key companies specializing in Alzheimer's disease - page 138
- Axonyx - page 138
- Mindset - page 140
- Strategies for success - page 141
- High risk, high profit versus low risk, low return - page 141
- Diagnosis of Alzheimer's disease - page 142
- Pipeline overview - page 127
- CHAPTER 7 BETA-AMYLOID MODULATORS - LATE-STAGE PIPELINE ANALYSIS & FORECASTS - page 145
- Overview for beta-amyloid modulators - page 145
- Pipeline summary - page 145
- Definition of current comparator therapy - page 145
- Alzhemed - page 146
- Drug overview - page 146
- Clinical trial data - page 148
- Phase I - page 148
- Phase II - page 148
- Phase III - page 150
- Patient potential - page 151
- Marketing factors - page 151
- Satisfaction of unmet need - page 152
- Efficacy - page 152
- Disease modification - page 152
- Safety - page 152
- Treatment response - page 152
- Forecasts to 2014 - page 153
- Datamonitor comments - page 154
- Flurizan ((R) - flurbiprofen) - page 154
- Clinical trial data - page 155
- Phase I - page 155
- Phase II - page 156
- Phase III - page 157
- Patient population - page 159
- Marketing factors - page 159
- Satisfaction of unmet needs - page 159
- Efficacy - page 159
- Disease modification - page 160
- Safety - page 160
- Treatment response - page 160
- Forecasts to 2014 - page 161
- Clinical trial data - page 155
- Other drugs - page 162
- AAB-001 - page 162
- Cereact/ONO-2506 - page 163
- LY-450139 - page 163
- Gero-46 (clioquinol) - page 164
- Late-stage development compounds recently discontinued - page 164
- PBT-1 (clioquinol) - page 164
- PPI-1019/Apan - page 166
- Comparison of key compounds in the beta-amyloid modulator class - page 167
- Disease modification - page 167
- Better efficacy than marketed drugs - page 167
- Side-effect profile - page 167
- Treatment unresponsive patients - page 167
- Marketing strength - page 168
- Commercial comparison - page 168
- Comparative forecasts - page 169
- Overview for beta-amyloid modulators - page 145
- CHAPTER 8 ACETYLCHOLINE MODULATORS - LATE-STAGE PIPELINE ANALYSIS AND FORECASTS - page 170
- Overview for acetylcholine modulators - page 170
- Pipeline summary - page 170
- Definition of current comparator therapy - page 170
- Phenserine - page 171
- Clinical trial data - page 171
- Phase I - page 171
- Phase II - page 172
- Phase IIb - page 172
- Phase III - page 173
- Patient profile - page 175
- Marketing factors - page 175
- Satisfaction of unmet needs - page 176
- Efficacy - page 176
- Treatment response - page 177
- Forecast to 2014 - page 177
- Clinical trial data - page 171
- Other drugs - page 177
- ZT-1 - page 177
- CI-1017 - page 178
- T-588 - page 178
- TV-3326 - page 179
- Dimebon - page 179
- Late-stage development compounds recently discontinued - page 180
- NS-2330 - page 180
- MKC-231 - page 181
- SIB-1553A - page 181
- Overview for acetylcholine modulators - page 170
- CHAPTER 9 NMDA MODULATORS - LATE-STAGE PIPELINE ANALYSIS AND FORECASTS - page 183
- Overview for NMDA modulators - page 183
- Pipeline summary - page 183
- Definition of current comparator therapy - page 183
- Neramexane - page 183
- Clinical trial data - page 184
- Phase III - page 184
- Phase II/ III - page 184
- Patient profile - page 186
- Marketing factors - page 186
- Satisfaction of unmet needs - page 187
- Efficacy - page 187
- Safety - page 187
- Treatment response - page 187
- Forecasts to 2014 - page 188
- Clinical trial data - page 184
- Other drugs - page 190
- Overview for NMDA modulators - page 183
- CHAPTER 10 NEUROPROTECTANTS - LATE-STAGE PIPELINE ANALYSIS AND FORECASTS - page 191
- Overview for neuroprotectant drugs - page 191
- Pipeline summary - page 191
- Definition of current comparator therapy - page 191
- Xaliproden (Xaprila) - page 192
- Profile - page 192
- Preclinical data - page 192
- Clinical trial data - page 193
- Datamonitor comments - page 193
- Phase III - page 193
- Patient profile - page 194
- Marketing factors - page 194
- Efficacy - page 194
- Disease modification - page 195
- Safety - page 195
- Treatment response - page 195
- Forecasts to 2014 - page 195
- EGb-761 (Tanakan) - page 196
- Profile - page 196
- Clinical trial data - page 196
- Phase III - The GEM Study - page 198
- Phase III - The Guidance Study - page 198
- Other drugs - page 199
- PYM50028 (Cogane) - page 199
- Clinical trial data - page 199
- Marketing factors - page 201
- SR-57667 - page 201
- Ampalex/CX516 - page 202
- CX717 - page 203
- Epadel/MND-21 - page 203
- SRA-333 (lecozotan) - page 204
- LY-451395 - page 204
- SL65.0155 - page 204
- PYM50028 (Cogane) - page 199
- Overview for neuroprotectant drugs - page 191
- CHAPTER 11 OTHER DRUGS - LATE-STAGE PIPELINE ANALYSIS AND FORECASTS - page 206
- Overview for other drugs - page 206
- Pipeline summary - page 206
- The role of statins in AD is not yet clear - page 206
- Zocor - page 207
- Lipitor - page 208
- Colostrinin - page 209
- Clinical trial data - page 209
- AC-3933/AVE-3933 - page 211
- Avandia (rosiglitazone) - page 211
- Evista (raloxifene) - page 212
- TVP-1012 (rasagiline) - page 212
- SGS-742 - page 212
- C-1073/Corlux - page 213
- C-9136 - page 213
- Memryte (leuprolide implant) - page 213
- Overview for other drugs - page 206
- CHAPTER 12 INNOVATIVE EARLY-STAGE PROJECTS - page 215
- Immunotherapy and vaccines - page 215
- AN-1792 showed promise but fell on safety issues - page 215
- Evidence of Aβ clearance, but effects on cognition not clear - page 216
- New immunotherapeutic approaches reignite hope for an 'Alzheimer's vaccine' - page 216
- AAB-001 - page 217
- ACC-001 - page 217
- CAD-106 - page 217
- AutoVac for Alzheimer's PX-106 - page 217
- PeviPro - page 218
- Mindset's β-amyloid antibodies - page 218
- M266 - page 219
- Considerations for immunotherapeutic approaches - page 219
- Immunotherapy and vaccines - page 215
- CHAPTER 13 FORECAST ANALYSIS - page 220
- Assumptions and events - page 220
- 2005 - page 220
- EU approval of liquid Aricept will increase its use in severe AD - page 220
- EU decision on the use of Namenda in mild to moderate AD - page 220
- 2006 - page 221
- NICE to publish its final guidance on AD drugs - page 221
- Aricept set to become the first US full-spectrum AD drug - page 222
- The first transdermal AChEI to be filed - page 222
- 2007 - page 223
- Assessment of xaliproden (Xaprila) - page 223
- Novartis aims to differentiate with ExelonTDS - page 223
- 2008 - page 223
- AChEI generics enter the US market - page 223
- 2009 - page 224
- A new generation of AD products - Alzhemed launched in the US - page 224
- Flurizan's US uptake not expected to be as strong as that of Alzhemed - page 225
- Memantine finally becomes available in Japan - page 226
- Generic memantine becomes available in Germany and Spain - page 226
- Razadyne makes its entry in Japan - page 226
- 2010 - page 226
- Alzhemed available for use in Europe - page 226
- Flurizan launched in the EU - page 227
- Generic donepezil becomes available in the US - page 227
- 2011 - page 227
- Generic memantine becomes available in the US - page 227
- The impact of memantine generics may be reduced by neramexane's entry in the US - page 228
- The last of the AChEIs, Exelon, goes off patent in the US - page 228
- Generic rivastigmine launches in Germany - page 229
- 2012 - page 230
- Forest launches neramexane across the EU - page 230
- European AChEIs get hit by generics - page 230
- Generic rivastigmine launches in France and the UK - page 230
- The Japanese market washed out as Aricept's patent expires - page 230
- 2013 - page 231
- Generic rivastigmine launches in Italy and Spain - page 231
- 2014 - page 231
- Generic rivastigmine finally becomes available in the US - page 231
- Generic memantine becomes available in the remaining major EU markets - page 231
- 2005 - page 220
- Assumptions and events - page 220
- CHAPTER 14 COMMERCIAL IMPACT AND LIFECYCLE MANAGEMENT: CASE STUDIES - page 232
- Case studies - page 232
- Managing the product lifecycle for maximum revenues - page 232
- Formulations not yet tested in the AD market - page 233
- Demonstrating the benefits of combinations can be a source of gains - page 235
- Phase II drugs may limit the success of Alzhemed and Flurizan - page 236
- Managing the product lifecycle for maximum revenues - page 232
- Case studies - page 232
- APPENDIX A - page 239
- AD market data - page 239
- Preclinical drug pipeline - page 246
- Bibliography - page 250
- APPENDIX B - page 259
- AD drug revenue forecasts by country - page 259
- Report methodology - page 267
- Standard Units - page 267
- Japanese Market Data - page 267
- Derivation of Sales Forecasts and Pricing Trends - page 267
- Regional Launch Dates for New Products - page 268
- Generic Erosion and Pricing Assumptions - page 268
- ABOUT DATAMONITOR - page 269
- Disclaimer - page 272
- List of Tables
- Table 1: Key parameters of AD - page 6
- Table 2: Forecast key pipeline products in AD from 2010-14 - page 6
- Table 3: Common clinical features in Alzheimer's disease by stage - page 28
- Table 4: Prevalence for moderate and severe AD only - page 29
- Table 5: Population estimates for moderate and severe AD (millions), 1995-2050 - page 29
- Table 6: AD comorbidity trials of existing drugs - page 35
- Table 7: DSM-IV criteria for Alzheimer's type dementia - page 37
- Table 8: Diagnosis rates across the seven major markets, 2005 - page 38
- Table 9: Drug-treated AD populations across the seven major markets, 2005 - page 39
- Table 10: Prevalence of Alzheimer's disease by gender and age - page 40
- Table 11: Prevalence of Alzheimer's disease across the seven major markets, 2005 - page 42
- Table 12: AD population across the seven major markets (millions), 1995-2050 - page 43
- Table 13: Global AD drug revenues, 2004 - page 47
- Table 14: US AD drug market, 2004 - page 63
- Table 15: AD drug market in Japan, 2004 - page 71
- Table 16: AD drug market in France, 2004 - page 77
- Table 17: AD drug market in Germany, 2004 - page 83
- Table 18: AD drug market in Italy, 2004 - page 89
- Table 19: AD drug market in Spain, 2004 - page 96
- Table 20: UK AD drug market, 2004 - page 102
- Table 21: Measures used for clinical efficacy endpoints in AD - page 123
- Table 22: AD drugs in Phase III clinical development, 2005 - page 128
- Table 23: AD drugs in Phase II clinical development, 2005 - page 131
- Table 24: AD drugs in Phase I clinical development, 2005 - page 133
- Table 25: Eli Lilly's AD pipeline, 2005 - page 136
- Table 26: Sanofi-Aventis's AD pipeline, 2005 - page 137
- Table 27: Axonyx's AD pipeline, 2005 - page 140
- Table 28: Mindset's pipeline, 2005 - page 141
- Table 29: Aβ modulators in late-stage development 2005 - page 145
- Table 30: Global revenue forecasts for Alzhemed, 2005-14 - page 153
- Table 31: Impacting factors on the revenues of Alzhemed, 2005-14 - page 154
- Table 32: Global revenue forecasts for Flurizan, 2005-14 - page 161
- Table 33: Impacting factors on the revenues of Flurizan, 2005-14 - page 162
- Table 34: Discontinued R&D projects in the Beta-Amyloid modulator class, 2004-05 - page 164
- Table 35: Global sales forecasts for Aβ modulator drugs, 2006-14 - page 169
- Table 36: ACh modulators in late-stage development, 2005 - page 170
- Table 37: Discontinued R&D projects in the ACh modulator class, 2004-05 - page 180
- Table 38: NMDA modulators in late-stage development 2005 - page 183
- Table 39: Global sales forecasts for neramexane, 2005-14 - page 189
- Table 40: Impacting factors on the revenues of neramexane, 2005-14 - page 189
- Table 41: Neuroprotectant drugs in late-stage development, 2005 - page 191
- Table 42: Other drugs in late stage development, 2005 - page 206
- Table 43: Aricept key facts - page 239
- Table 44: Key Aricept events, 2004-2005 - page 240
- Table 45: Razadyne/ Razadyne ER key facts - page 241
- Table 46: Key Razadyne/ Razadyne ER events, 2004-2005 - page 241
- Table 47: Exelon key facts - page 242
- Table 48: Namenda key facts - page 243
- Table 49: Key Namenda events, 2004-2005 - page 244
- Table 50: AD drugs in preclinical development, 2005 - page 246
- Table 51: AD drug comparator score sheet - page 248
- Table 52: US AD drug revenue forecast - page 259
- Table 53: Japan AD drug revenue forecast - page 260
- Table 54: France AD drug revenue forecast - page 260
- Table 55: Germany AD drug revenue forecast - page 261
- Table 56: Italy AD drug revenue forecast - page 262
- Table 57: Spain AD drug revenue forecast - page 263
- Table 58: UK AD drug revenue forecast - page 264
- Table 59: EU5 AD drug revenue forecast - page 265
- Table 60: Global AD drug revenue forecast - page 266
- List of Figures
- Figure 1: AD population across the seven major markets, 1995-2050 - page 44
- Figure 2: Total global quarterly AD drug sales, 1999-2005 - page 46
- Figure 3: Global quarterly AD drug sales, 1999-2005 - page 47
- Figure 4: AD drug share by revenue across the seven major markets, 1999-2005 - page 48
- Figure 5: Key players in the AD market - page 54
- Figure 6: Importance of unmet needs in AD - page 55
- Figure 7: AD relative treatment ratios - page 59
- Figure 8: AD drug market, quarterly revenues, 1999-2005 - page 64
- Figure 9: US AD market share, by revenue, 1999-2005 - page 65
- Figure 10: AD drug market in Japan, quarterly revenues, 1999-2005 - page 71
- Figure 11: AD drug market in France, quarterly revenues, 1999-2005 - page 78
- Figure 12: AD market share in France, by revenue, 1999-2005 - page 79
- Figure 13: AD drug market in Germany, quarterly revenues, 1999-2005 - page 84
- Figure 14: AD market share in Germany, by revenue, 1999-2005 - page 85
- Figure 15: AD drug market in Italy, quarterly revenues, 1999-2005 - page 90
- Figure 16: AD market share in Italy, by revenue, 1999-2005 - page 91
- Figure 17: AD drug market in Spain, quarterly revenues, 1999-2005 - page 97
- Figure 18: AD market share in Spain, by revenue, 1999-2005 - page 98
- Figure 19: AD drug market in the UK quarterly revenues, 1999-2005 - page 103
- Figure 20: AD market share in the UK, by revenue, 1999-2005 - page 104
- Figure 21: AD pipeline drugs in each development stage by class - page 127
- Figure 22: Alzhemed's satisfaction of unmet needs - page 153
- Figure 23: Flurizan's satisfaction of unmet needs - page 161
- Figure 24: Commercial comparison of beta-amyloid modulators Alzhemed and Flurizan against gold standard Aricept - page 168
- Figure 25: Commercial comparison of NMDA modulator neramexane against gold standard Namenda - page 188
- Figure 26: Potential impact of Phase II drugs on US forecasts - page 236
- Figure 27: US forecast for pipeline drugs without Phase II drug impact - page 237
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