Alzheimer's Disease - Diagnosis, Disease Modification and Prevention Key to Growing Market
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
- Scope of the analysis - page 3
- Datamonitor insight into the Alzheimer's disease market - page 4
- The major unmet need in this market is for disease modification and disease prevention. Currently marketed products are perceived to only provide partial and temporary relief from Alzheimer's symptoms. In the short to medium term opinion leaders are looking to Axonyx's phenserine and Neurochem's Alzhemed in anticipation of successful modification of disease progression. This high level of awareness and positivity bodes well for the launches of these products, which could challenge the market domination of Pfizer/Eisai's Aricept (donepezil) if supported by sufficient marketing strength. - page 5
- Current diagnosis by specialists, albeit of 'probable' Alzheimer's, is relatively accurate as verified on post mortem analysis. However, an increasing focus on early identification and prevention, in addition to a growing aging population being managed by primary care physicians, highlights a need for simpler diagnostic tools and robust biological markers. Improved identification of both 'at risk' and early clinical groups would aid trial design and assist patient segmentation and product positioning strategies, which will become key as more players enter the market. - page 8
- Prevention is better than cure. Over the longer term physicians, and sections of the pharmaceutical industry, are searching for options to prevent Alzheimer's disease. The large number of mechanisms hypothesized to contribute to the etiology and progression of the disorder complicates this quest. As these hypotheses are refined and scientific rationale is demonstrated, the substantial opportunity provided by prevention may become more attainable, however Industry will need to pay careful consideration to the challenges of a prophylactic market. - page 10
- Although neuroprotective and neurotrophic drugs offer significant potential commercial benefit, they are also associated with problematic development. Companies with little threshold tolerance for pipeline failure may look to balance their risk across a number of potential pathways to Alzheimer's treatment. This approach will increase the likelihood of providing a marketable product and could provide a veritable suite of drugs for Alzheimer's management across the patients' range of needs. - page 14
- Summary - page 16
- Key metrics - page 17
- CHAPTER 2 PATIENT POTENTIAL - page 32
- Definition of Alzheimer's disease - page 33
- Segmentation of Alzheimer's disease - page 35
- Mild cognitive impairment (MCI) - page 35
- Comorbidities - page 36
- Treatments for comorbidities - page 37
- Drugs for treating depression - page 37
- Drugs for treating agitation, aggression and psychotic symptoms - page 37
- Drugs for treating anxiety - page 38
- Drugs for treating sleep disturbances - page 38
- Commercial analysis of AD comorbidities - page 39
- Treatments for comorbidities - page 37
- Epidemiology of Alzheimer's disease - page 40
- Diagnosis and treatment rates - page 41
- Future trends - page 42
- Unmet needs in Alzheimer's disease - page 43
- Disease modification - page 43
- Improved efficacy - page 43
- Fewer side effects - page 44
- Reducing numbers of treatment unresponsive patients - page 45
- Patient compliance - page 45
- CHAPTER 3 R&D APPROACH - page 46
- Classification of pipeline products - page 47
- ACh modulators - page 47
- Neuroprotective and neurotrophic drugs - page 49
- Beta-amyloid modulators - page 50
- Beta-secretase (BACE) inhibitors - page 50
- Protein deposition inhibitors - page 50
- Other compounds in development - page 50
- Clinical trial design in Alzheimer's disease - page 51
- Patient population - page 51
- Design - page 52
- Duration - page 52
- Gold standard - page 53
- Clinical trial endpoints in Alzheimer's disease - page 53
- Alzheimer's disease assessment scale - page 55
- Mini-Mental Status Exam - page 55
- Clinician's Interview-Based Impression of Change - page 56
- Severe Impairment Battery - page 56
- Alzheimer's Disease Cooperative Study: Activities of Daily Living - page 56
- Clinical Dementia Rating - page 57
- Cambridge Neuropsychological Test Automated Battery (CANTAB) - page 57
- Global Deterioration Scale - page 59
- Functional Assessment Staging - page 60
- Clinical Global Impression of Change - page 61
- Clinical Global Impression of Severity - page 61
- Neuropsychiatry Inventory - page 62
- Behavioral Rating Scale for Geriatric Patients - page 62
- Resource Utilization in Dementia - page 63
- Disability Assessment for Dementia - page 63
- Progressive Deterioration Scale - page 63
- Clinical Dementia Rating - page 64
- Summary - page 64
- Classification of pipeline products - page 47
- CHAPTER 4 ALZHEIMER'S DISEASE PIPELINE ANALYSIS - page 66
- Pipeline overview - page 67
- Phase III overview - page 68
- Phase II overview - page 70
- Phase I overview - page 72
- Preclinical overview - page 74
- Key companies involved in the Alzheimer's disease pipeline - page 77
- Eli Lilly - page 77
- Pfizer - page 78
- Sanofi-Synth�labo - page 79
- Companies specializing in Alzheimer's disease - page 81
- Axonyx - page 81
- Mindset - page 83
- Nymox - page 85
- Prana - page 87
- Strategies for success - page 88
- High risk, high profit versus low risk, low return - page 88
- Diagnosis of Alzheimer's disease - page 89
- Ethics and trial design - page 92
- Pipeline overview - page 67
- CHAPTER 5 ACETYLCHOLINE MODULATORS - LATE-STAGE DRUG ANALYSIS & FORECASTS - page 93
- Overview for ACh modulators - page 94
- Pipeline summary - page 94
- Definition of current comparator therapy - page 94
- Phenserine - page 95
- Profile - page 95
- Drug overview - page 95
- Clinical trial data - page 96
- Phase III - page 96
- Phase II - page 96
- Patient profile - page 98
- Marketing factors - page 98
- Satisfaction of unmet needs - page 100
- Efficacy - page 101
- Disease modification - page 101
- Safety - page 102
- Treatment response - page 102
- Forecasts to 2014 - page 102
- Profile - page 95
- Other ACh modulator drugs - page 103
- ZT-1 (Huperzine A) - page 103
- NS-2330 - page 106
- P58 - page 110
- TC-1734 - page 113
- SIB-1553A - page 114
- ABT-089 - page 115
- Ganstigmine - page 116
- CI-1017 (PD-151832) - page 117
- MKC231 - page 117
- Late-stage development compounds recently discontinued - page 118
- TAK-147 (PIII) - page 118
- Comparison of key AChE modulator compounds - page 119
- Disease modification - page 119
- Better efficacy than marketed drugs - page 120
- Side-effect profile - page 120
- Treatment unresponsive patients - page 120
- Marketing strength - page 120
- Overview for ACh modulators - page 94
- CHAPTER 6 BETA-AMYLOID MODULATORS LATE-STAGE DRUG ANALYSIS AND FORECASTS - page 122
- Overview for beta-amyloid modulators - page 123
- Pipeline summary - page 123
- Definition of current comparator therapy - page 123
- Alzhemed (NC 531) - page 123
- Profile - page 123
- Drug overview - page 123
- Clinical trial data - page 124
- Phase I - page 124
- Phase II - page 125
- Phase III - page 126
- Patient potential - page 127
- Marketing factors - page 127
- Satisfaction of unmet need - page 127
- Efficacy - page 127
- Disease modification - page 128
- Safety - page 128
- Treatment response - page 128
- Forecasts to 2014 - page 129
- Profile - page 123
- PBT-1 (clioquinol) - page 130
- Profile - page 130
- Drug overview - page 130
- Clinical trial data - page 131
- PHASE II TRIAL - page 131
- Patient potential - page 134
- Marketing factors - page 134
- Satisfaction of unmet need - page 135
- Efficacy - page 135
- Disease modification - page 135
- Safety - page 135
- Treatment response - page 135
- Forecasts to 2014 - page 136
- Profile - page 130
- Other drugs - page 138
- Egb-761 (Tanakan) - page 138
- Comparison of key compounds in the beta-amyloid modulator class - page 140
- Disease modification - page 140
- Better efficacy than marketed drugs - page 140
- Side-effect profile - page 140
- Treatment unresponsive patients - page 141
- Marketing strength - page 142
- Comparative forecasts - page 142
- Overview for beta-amyloid modulators - page 123
- CHAPTER 7 NEUROPROTECTIVE AND NEUROTROPHIC DRUGS-LATE-STAGE DRUG ANALYSIS AND FORECASTS - page 143
- Overview for neuroprotective and neurotrophic drugs - page 144
- Pipeline summary - page 144
- Definition of current comparator therapy - page 144
- Xaliproden - page 144
- Profile - page 144
- Drug overview - page 144
- Clinical trial data - page 145
- Patient potential - page 146
- Marketing factors - page 146
- Satisfaction of unmet need - page 147
- Efficacy - page 147
- Disease modification - page 148
- Safety - page 148
- Treatment response - page 148
- Forecasts to 2014 - page 148
- Profile - page 144
- Other drugs - page 148
- SR-57667 - page 148
- SGS111 - page 149
- KA-672 - page 150
- T-588 - page 151
- Late-stage development compounds recently discontinued - page 152
- CX516 (AMPAKINE) (PII) - page 152
- FK960 (PII) - page 153
- Neotrofin (PII) - page 153
- Overview for neuroprotective and neurotrophic drugs - page 144
- CHAPTER 8 OTHER DRUGS - LATE-STAGE DRUG ANALYSIS AND FORECASTS - page 155
- Overview for other drugs - page 156
- Pipeline summary - page 156
- Definition of current comparator therapy - page 156
- Antioxidants - page 157
- Colostrinin - page 157
- Drug profile - page 157
- Clinical trial data - page 158
- PHASE II/III - page 158
- Patient potential - page 160
- Marketing factors - page 160
- Satisfaction of unmet needs - page 160
- EFFICACY - page 161
- DISEASE MODIFICATION - page 161
- SAFETY - page 161
- TREATMENT RESPONSE - page 162
- Forecasts to 2014 - page 162
- Bacosides - page 163
- Colostrinin - page 157
- Vitamin E - page 163
- PREADVISE - page 163
- Vitamin E and donepezil - page 164
- Anti-inflammatory drugs - page 165
- R-Flurbiprofen (MPC7869) - page 166
- Dapsone - page 167
- Statins - page 169
- Lipitor (atorvastatin) - page 170
- Zocor (simvastatin) - page 171
- Comment - page 171
- B vitamins - page 172
- Hormones - page 172
- Estrogen - page 173
- Drug overview - page 173
- Clinical trial data - page 175
- PHASE III TRIAL 1: WOMEN'S HEALTH INITIATIVE MEMORY STUDY (WHIMS) (SHUMAKER ET AL., 2003; BARCLAY, 2004; SHUMAKER ET AL., 2004) - page 175
- PHASE III TRIAL 2: THAL ET AL., 2003 - page 175
- PHASE III TRIAL 3: MULNARD ET AL., 2000 - page 176
- Datamonitor conclusions - page 176
- Leuprolide - page 177
- Testosterone - page 177
- Estrogen - page 173
- Rasagiline - page 179
- Avandia (rosiglitazone) - page 180
- SGS-742 - page 181
- SL-65.0155 - page 181
- S-8510 - page 182
- COGNIShunt - page 183
- Late-stage development compounds recently discontinued - page 185
- NSAIDs (Vioxx, Naprelan) (PIII) - page 185
- Lovastatin (ADX-159) (PII) - page 185
- Comparison of key compounds in the other drugs class - page 186
- Disease modification - page 186
- Better efficacy than marketed drugs - page 187
- Side-effect profile - page 187
- Marketing strength - page 187
- Overview for other drugs - page 156
- CHAPTER 9 INNOVATIVE EARLY-STAGE PROJECTS - page 188
- Key Phase I and preclinical compounds in Alzheimer's disease - page 189
- Chelators - page 189
- Gene therapy - page 191
- HCT 1026 - page 193
- Lithium - page 194
- Ketone bodies - page 195
- AMPAKINES - page 195
- CX-717 - page 196
- S-18986 - page 196
- Vaccines - page 196
- Neurochem - page 197
- Elan and Wyeth: ACC-001 - page 198
- Mindset: Amyrex - page 198
- Pharmexa and Lundbeck: PX-106 - page 199
- Cytos and Novartis: AD Immunodrug - page 200
- Other vaccines - page 200
- Comments - page 200
- VACCINES CAN BE PRICED AT A PREMIUM LEVEL - page 201
- BARRIERS TO THE USE/DEVELOPMENT OF VACCINES IN AD - page 201
- LONG-TERM SAFETY ISSUE OF VACCINES - page 202
- Key research impacts on Alzheimer's disease - page 202
- Amyloid and blood vessels in the brain - page 202
- APPENDIX A - page 205
- Contributing experts - page 205
- Bibliography - page 205
- General information - page 205
- Epidemiology - page 212
- Clinical trial data - page 212
- Websites - page 216
- Report methodology - page 220
- Introduction - page 220
- Hypothesis formulation - page 220
- Hypothesis testing - page 221
- Ongoing information update - page 221
- Product specific primary research - page 221
- Data verification and quality control - page 222
- Quantification of data reliability - page 222
- Confidence ratings - page 222
- Date of research completion - page 223
- Introduction to Datamonitor Healthcare forecasting - page 223
- Methodology - page 223
- Market events - page 224
- Validation - page 226
- Pipeline-drug forecast methodology - page 226
- Predicting initial market share - page 227
- Clinical competitiveness attributes - page 227
- Order of entry - page 227
- Pre-launch awareness - page 227
- Market composition - page 228
- Marketing plan - page 228
- Marketing strength - page 228
- Forecasting future growth - page 228
- Influencing factors - page 228
- Predicting initial market share - page 227
- APPENDIX B - page 230
- About Datamonitor - page 230
- About Datamonitor Healthcare - page 230
- Datamonitor Healthcare's therapy area capabilities - page 231
- About the CNS analysis team - page 232
- Key therapy team members - page 233
- Disclaimer - page 234
- About Datamonitor - page 230
- List of Tables
- Table 1: Key parameters of Alzheimer's disease - page 17
- Table 2: Forecast key pipeline products in Alzheimer's disease, 2004-14 - page 17
- Table 3: AD comorbidity trials of existing drugs - page 39
- Table 4: Prevalence of Alzheimer's disease across the seven major markets, 2003 - page 40
- Table 5: AD prevalence rates by age group - page 41
- Table 6: Diagnosis rates across the seven major markets, 2004 - page 41
- Table 7: Drug-treated populations across the seven major markets, 2004 - page 42
- Table 8: Measures used for clinical efficacy endpoints in AD - page 54
- Table 9: Phase III pipeline in AD, 2004 - page 68
- Table 10: Phase II pipeline in AD, 2004 - page 70
- Table 11: Phase I pipeline in AD, 2004 - page 72
- Table 12: Preclinical pipeline in AD, 2004 - page 74
- Table 13: Preclinical pipeline in AD, 2004 [continued] - page 75
- Table 14: Preclinical pipeline in AD, 2004 [continued] - page 76
- Table 15: Eli Lilly's AD pipeline, 2004 - page 78
- Table 16: Pfizer's AD pipeline, 2004 - page 79
- Table 17: Sanofi-Synthelabo's AD pipeline, 2004 - page 81
- Table 18: Axonyx's AD pipeline, 2004 - page 83
- Table 19: Mindset's AD pipeline, 2004 - page 85
- Table 20: Nymox's AD pipeline, 2004 - page 86
- Table 21: Prana's AD pipeline, 2004 - page 88
- Table 22: Key products in late-stage R&D pipeline for ACh modulators, 2004 - page 94
- Table 23: Clinical trial summary: Phenserine - page 99
- Table 24: Global sales forecasts for phenserine - page 103
- Table 25: Impacting factors on the revenues of phenserine, 2004-14 - page 103
- Table 26: Key products in late-stage R&D pipeline for Aβ modulators, 2004 - page 123
- Table 27: Global sales forecasts for Alzhemed - page 129
- Table 28: Impacting factors on the revenues of Alzhemed, 2004-14 - page 129
- Table 29: Global sales forecasts for PBT-1 - page 137
- Table 30: Impacting factors on the revenues of PBT-1, 2004-2014 - page 137
- Table 31: Global sales forecasts for Aβ modulator drugs, 2004-12 - page 142
- Table 32: Key products in late-stage R&D pipeline for neuroprotective and neurotrophic drugs, 2004 - page 144
- Table 33: Key products in late-stage R&D pipeline for other drugs group, 2004 - page 156
- Table 34: Global sales forecasts for Colostrinin - page 162
- Table 35: Impacting factors on the revenues of Colostrinin, 2004-14 - page 162
- Table 36: Drugs in Phase I and preclinical development for AD, 2004 - page 189
- Table 37: Confidence ratings for R&D pipeline data - page 222
- List of Figures
- Figure 1: Alzheimer's disease impacts to 2014 - page 16
- Figure 2: Importance of unmet needs - page 44
- Figure 3: Drug class by development stage. - page 67
- Figure 4: Phenserine's satisfaction of unmet needs - page 101
- Figure 5: Comparative strengths of key ACh modulators - page 119
- Figure 6: Alzhemed's satisfaction of unmet needs - page 128
- Figure 7: PBT-1's satisfaction of unmet needs - page 136
- Figure 8: Comparative strengths of key Aβ modulators - page 141
- Figure 9: Colostrinin's satisfaction of unmet needs - page 161
- Figure 10: Comparison of key "other" drugs - page 186
- Figure 11: ACC-001's mechanism of action - page 198
- Figure 12: Market events affecting baseline product forecasts - page 224
- Figure 13: Algorithm depicting key consitiuent variables upon which drug revenues depend - page 225
- Figure 14: Overview of Datamonitor Healthcare's forecasting approach for pipeline drugs - page 226
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