CONTENTS

11 FORECAST: ALZHEIMER’S DISEASE (Published on 21 June 2017)
11 OVERVIEW
12 EXECUTIVE SUMMARY
13 MARKET OVERVIEW AND TRENDS
25 MARKET DEFINITION AND METHODOLOGY
31 ADUCANUMAB
36 ARICEPT (DONEPEZIL)
39 CRENEZUMAB
44 EXELON/EXELON PATCH (RIVASTIGMINE)
47 NAMENDA/XR (MEMANTINE)
51 RAZADYNE (GALANTAMINE)
54 RVT-101
57 PRIMARY RESEARCH METHODOLOGY

60 TREATMENT: ALZHEIMER’S DISEASE (Published on 21 June 2017)
60 OVERVIEW
61 EXECUTIVE SUMMARY
62 PRIMARY RESEARCH METHODOLOGY
64 DISEASE DEFINITION AND DIAGNOSIS
77 PATIENT SEGMENTATION
84 COUNTRY TREATMENT TREES
85 CURRENT TREATMENT OPTIONS
90 PRESCRIBING TRENDS
113 UNMET NEEDS IN ALZHEIMER’S DISEASE

129 EPIDEMIOLOGY: ALZHEIMER’S DISEASE IN BRAZIL (Published on 01 November 2013)
129 OVERVIEW
130 EXECUTIVE SUMMARY
131 DISEASE DEFINITION AND DIAGNOSIS
137 GLOBAL VARIATIONS
140 RISK FACTORS
145 SOURCES AND METHODOLOGY
148 FORECAST
153 DISCUSSION
155 BIBLIOGRAPHY

161 EPIDEMIOLOGY: ALZHEIMER’S DISEASE IN THE US, JAPAN, AND 5EU (Published on 09 May 2018)
161 OVERVIEW
162 DISEASE BACKGROUND
163 METHODOLOGY
166 FORECAST
171 BIBLIOGRAPHY
172 APPENDIX: MILD COGNITIVE IMPAIRMENT

177 MARKETED DRUGS: ALZHEIMER’S DISEASE (Published on 21 June 2017)
177 OVERVIEW
178 EXECUTIVE SUMMARY
179 PRODUCT OVERVIEW
181 PRODUCT PROFILE: ARICEPT
191 PRODUCT PROFILE: EXELON/EXELON PATCH
203 PRODUCT PROFILE: NAMENDA
212 PRODUCT PROFILE: RAZADYNE

220 PIPELINE: ALZHEIMER’S DISEASE (Published on 21 June 2017)
220 OVERVIEW
221 EXECUTIVE SUMMARY
223 CLINICAL PIPELINE OVERVIEW
226 CLINICAL TRIAL DESIGN
239 RECENTLY DISCONTINUED DRUGS
246 PRODUCT PROFILE (LATE STAGE): LMTX
259 PRODUCT PROFILE (LATE STAGE): RVT-101
272 PRODUCT PROFILE (LATE STAGE): ADUCANUMAB
284 PRODUCT PROFILE (LATE STAGE): AZELIRAGON
296 PRODUCT PROFILE (LATE STAGE): CRENEZUMAB
307 PRODUCT PROFILE (LATE STAGE): GANTENERUMAB
316 PRODUCT PROFILE (LATE STAGE): VERUBECESTAT

LIST OF FIGURES
13 Figure 1: Alzheimer’s disease market sales value in the US, Japan, and five major EU markets, by country, 2015−24
16 Figure 2: Alzheimer’s disease drug class sales in the US, Japan, and five major EU markets, 2015−24
18 Figure 3: Sales of cholinesterase inhibitors in the US, Japan, and five major EU markets, by country, 2015−24
20 Figure 4: Sales of NMDA receptor antagonists in the US, Japan, and five major EU markets, by country, 2015−24
23 Figure 5: Alzheimer’s disease market sales value by disease severity in the US, Japan, and five major EU markets, 2015−24
26 Figure 6: Patient-based forecast methodology for Alzheimer’s disease
27 Figure 7: Price sources and calculations, by country
33 Figure 8: Aducanumab sales for Alzheimer’s disease across the US, Japan, and five major EU markets, by country, 2015−24
37 Figure 9: Aricept sales for Alzheimer’s disease across the US, Japan, and five major EU markets, by country, 2015−24
41 Figure 10: Crenezumab sales for Alzheimer’s disease across the US, Japan, and five major EU markets, by country, 2015−24
45 Figure 11: Exelon/Exelon Patch sales for Alzheimer’s disease across the US, Japan, and five major EU markets, by country, 2015−24
48 Figure 12: Namenda/XR sales for Alzheimer’s disease across the US, Japan, and five major EU markets, by country, 2015−24
52 Figure 13: Razadyne sales for Alzheimer’s disease across the US, Japan, and five major EU markets, by country, 2015−24
55 Figure 14: RVT-101 sales for Alzheimer’s disease across the US, Japan, and five major EU markets, by country, 2015−24
66 Figure 15: Hypothetical model of dynamic biomarkers taking place with disease severity
67 Figure 16: Neurologist-reported Alzheimer’s disease diagnosis rates, by country, 2015
69 Figure 17: Hypothesized beta-amyloid pathway in Alzheimer’s disease and therapeutic strategies
70 Figure 18: Hypothesized tau pathway in Alzheimer’s disease and therapeutic strategies
74 Figure 19: The dynamics in biomarkers of the Alzheimer’s disease pathological cascade
78 Figure 20: Estimated prevalent and diagnosed prodromal and Alzheimer’s disease patient populations in the US, Japan, and
five major EU markets, by country, 2015
79 Figure 21: Diagnosed Alzheimer’s disease patients in the US, Japan, and five major EU markets, by disease severity and country, 2015
81 Figure 22: Estimated prevalent, diagnosed, and drug-treated prodromal and Alzheimer’s disease patients in the US, Japan, and five major EU markets, by country, 2015
82 Figure 23: Proportion of drug-treated patients in the US, Japan, and five major EU markets, by disease severity and country (%), 2015
90 Figure 24: Pharmacological treatment rates for diagnosed Alzheimer’s patients in the US, Japan, and five major EU markets, by disease severity and country (%), 2015
93 Figure 25: Treatment choices for patients diagnosed with prodromal Alzheimer’s disease in the US, Japan, and five major EU markets, by country (%), 2015
94 Figure 26: Treatment choices for patients diagnosed with mild Alzheimer’s disease in the US, Japan, and five major EU markets, by country (%), 2015
95 Figure 27: Treatment choices for patients diagnosed with moderate Alzheimer’s disease in the US, Japan, and five major EU markets, by country (%), 2015
96 Figure 28: Treatment choices for patients diagnosed with severe Alzheimer’s disease in the US, Japan, and five major EU markets, by country (%), 2015
97 Figure 29: Prescription trends in patients diagnosed with prodromal Alzheimer’s disease in the US, Japan, and five major EU markets, by country (%), 2015
100 Figure 30: Prescription trends in patients diagnosed with mild Alzheimer’s disease in the US, Japan, and five major EU markets, by country (%), 2015
103 Figure 31: Prescription trends in patients diagnosed with moderate Alzheimer’s disease in the US, Japan, and five major EU markets, by country (%), 2015
105 Figure 32: Prescription trends in patients diagnosed with severe Alzheimer’s disease in the US, Japan, and five major EU markets, by country (%), 2015
108 Figure 33: Preference for rivastigmine patch over oral formulation for all severities of Alzheimer’s disease, by country (%), 2015
109 Figure 34: Proportion of Alzheimer’s disease patients receiving either memantine monotherapy or in combination, by country (%), 2015
110 Figure 35: Compliance rates to oral versus transdermal patch formulations in patients with Alzheimer’s disease, by country (%), 2015
113 Figure 36: Key unmet needs for Alzheimer’s disease, 2015
115 Figure 37: Impact of symptomatic versus disease-modifying drugs on quality of life/life expectancy over the course of the disease
125 Figure 38: NHS’s recommended referral pathway for patients presenting to primary care with dementia
138 Figure 39: Age- and sex-specific incidence rates of Alzheimer’s disease in Japan
150 Figure 40: Prevalent Alzheimer’s disease cases in Brazil in the population aged 60+, by sex and age group, 2012
151 Figure 41: Trends in prevalent Alzheimer’s disease cases in Brazil in the population aged 60+, by age group, 2012–30
152 Figure 42: Trends in prevalent Alzheimer’s disease cases in Brazil in the population aged 60+, by geographic level, 2012–30
170 Figure 43: Trends in total prevalent cases of Alzheimer’s disease in the US, Japan, and five major EU markets, 2017–37
185 Figure 44: Aricept for Alzheimer’s disease – SWOT analysis
186 Figure 45: Datamonitor Healthcare’s drug assessment summary of Aricept in Alzheimer’s disease
187 Figure 46: Datamonitor Healthcare’s drug assessment summary of Aricept in Alzheimer’s disease
197 Figure 47: Exelon/Exelon Patch for Alzheimer’s disease – SWOT analysis
198 Figure 48: Datamonitor Healthcare’s drug assessment summary of Exelon in Alzheimer’s disease
199 Figure 49: Datamonitor Healthcare’s drug assessment summary of Exelon in Alzheimer’s disease
206 Figure 50: Namenda for Alzheimer’s disease – SWOT analysis
207 Figure 51: Datamonitor Healthcare’s drug assessment summary of Namenda in Alzheimer’s disease
208 Figure 52: Datamonitor Healthcare’s drug assessment summary of Namenda in Alzheimer’s disease
216 Figure 53: Razadyne for Alzheimer’s disease – SWOT analysis
217 Figure 54: Datamonitor Healthcare’s drug assessment summary of Razadyne in Alzheimer’s disease
218 Figure 55: Datamonitor Healthcare’s drug assessment summary of Razadyne in Alzheimer’s disease
235 Figure 56: Clinical trial designs proposed to determine disease modification
252 Figure 57: LMTX for Alzheimer’s disease – SWOT analysis
253 Figure 58: Datamonitor Healthcare’s drug assessment summary of LMTX in Alzheimer’s disease
254 Figure 59: Datamonitor Healthcare’s drug assessment summary of LMTX in Alzheimer’s disease
266 Figure 60: RVT-101 for Alzheimer’s disease – SWOT analysis
267 Figure 61: Datamonitor Healthcare’s drug assessment summary of RVT-101 in Alzheimer’s disease
268 Figure 62: Datamonitor Healthcare’s drug assessment summary of RVT-101 in Alzheimer’s disease
278 Figure 63: Aducanumab for Alzheimer’s disease – SWOT analysis
279 Figure 64: Datamonitor Healthcare’s drug assessment summary of aducanumab in Alzheimer’s disease
280 Figure 65: Datamonitor Healthcare’s drug assessment summary of aducanumab in Alzheimer’s disease
290 Figure 66: Azeliragon for Alzheimer’s disease – SWOT analysis
291 Figure 67: Datamonitor Healthcare’s drug assessment summary of azeliragon in Alzheimer’s disease
292 Figure 68: Datamonitor Healthcare’s drug assessment summary of azeliragon in Alzheimer’s disease
302 Figure 69: Crenezumab for Alzheimer’s disease – SWOT analysis
303 Figure 70: Datamonitor Healthcare’s drug assessment summary of crenezumab in Alzheimer’s disease
304 Figure 71: Datamonitor Healthcare’s drug assessment summary of crenezumab in Alzheimer’s disease
312 Figure 72: Gantenerumab for Alzheimer’s disease – SWOT analysis
313 Figure 73: Datamonitor Healthcare’s drug assessment summary of gantenerumab in Alzheimer’s disease
314 Figure 74: Datamonitor Healthcare’s drug assessment summary of gantenerumab in Alzheimer’s disease
321 Figure 75: Verubecestat for Alzheimer’s disease – SWOT analysis
322 Figure 76: Datamonitor Healthcare’s drug assessment summary of verubecestat in Alzheimer’s disease
323 Figure 77: Datamonitor Healthcare’s drug assessment summary of verubecestat in Alzheimer’s disease
324 Figure 78: Hypothetical model of dynamic biomarkers taking place with disease severity

LIST OF TABLES
14 Table 1: Alzheimer’s disease market sales value in the US, Japan, and five major EU markets, by country ($m), 2015−24
17 Table 2: Alzheimer’s disease drug class sales in the US, Japan, and five major EU markets ($m), 2015−24
19 Table 3: Sales of cholinesterase inhibitors in the US, Japan, and five major EU markets, by country ($m), 2015−24
21 Table 4: Sales of NMDA receptor antagonists in the US, Japan, and five major EU markets, by country ($m), 2015−24
24 Table 5: Alzheimer’s disease market sales value by disease severity in the US, Japan, and five major EU markets ($m), 2015–24
25 Table 6: Summary of drug classes and molecules in Datamonitor Healthcare’s Alzheimer’s disease patient-based forecast
28 Table 7: Exchange rates used for calculating prices
28 Table 8: Estimated patent expiry/loss of exclusivity dates for key marketed brands in Alzheimer’s disease in the US, Japan, and five major EU markets, by country
29 Table 9: Estimated launch dates of key late-stage pipeline products in Alzheimer’s disease, by country, 2015−24
32 Table 10: Aducanumab’s dose and price assumptions, by country, 2016
34 Table 11: Aducanumab sales for Alzheimer’s disease across the US, Japan, and five major EU markets, by country ($m), 2015−24
38 Table 12: Aricept sales for Alzheimer’s disease across the US, Japan, and five major EU markets, by country ($m), 2015−24
40 Table 13: Crenezumab’s dose and price assumptions, by country, 2016
42 Table 14: Crenezumab sales for Alzheimer’s disease across the US, Japan, and five major EU markets, by country ($m), 2015−24
46 Table 15: Exelon/Exelon Patch sales for Alzheimer’s disease across the US, Japan, and five major EU markets, by country ($m), 2015−24
49 Table 16: Namenda/XR sales for Alzheimer’s disease across the US, Japan, and five major EU markets, by country ($m), 2015−24
53 Table 17: Razadyne sales for Alzheimer’s disease across the US, Japan, and five major EU markets, by country ($m), 2015−24
56 Table 18: RVT-101 sales for Alzheimer’s disease across the US, Japan, and five major EU markets, by country ($m), 2015−24
57 Table 19: Neurologists surveyed for the Alzheimer’s disease primary research study, 2015
59 Table 20: Pipeline products discussed in the key opinion leader research interviews
62 Table 21: Neurologists surveyed for the Alzheimer’s disease primary research study, 2015
71 Table 22: Common clinical features of Alzheimer’s disease
73 Table 23: Dementia caregiver tasks
79 Table 24: Estimated number of diagnosed Alzheimer’s disease patients in the US, Japan, and five major EU markets, by disease severity and country, 2015
82 Table 25: Estimated number of drug-treated Alzheimer’s disease patients in the US, Japan, and five major EU markets, by disease severity and country, 2015
86 Table 26: Leading therapies for Alzheimer’s disease
87 Table 27: Commonly used guidelines for the treatment of Alzheimer’s disease
91 Table 28: Pharmacological treatment rates for diagnosed Alzheimer’s patients in the US, Japan, and five major EU markets, by disease severity and country (%), 2015
98 Table 29: Prescription trends in patients diagnosed with prodromal Alzheimer’s disease in the US, Japan, and five major EU markets, by country (%), 2015
101 Table 30: Prescription trends in patients diagnosed with mild Alzheimer’s disease in the US, Japan, and five major EU markets, by country (%), 2015
104 Table 31: Prescription trends in patients diagnosed with moderate Alzheimer’s disease in the US, Japan, and five major EU markets, by country (%), 2015
106 Table 32: Prescription trends in patients diagnosed with severe Alzheimer’s disease in the US, Japan, and five major EU markets, by country (%), 2015
117 Table 33: Summary of the global and cognitive response of Alzheimer’s disease patients to acetylcholinesterase inhibitor treatment
121 Table 34: Aricept’s side-effect profile
134 Table 35: DSM-IV-TR diagnostic criteria for 294.1x dementia of the Alzheimer’s type
136 Table 36: NINCDS-ADRDA criteria – probable AD
141 Table 37: Overview of risk factors for dementia, Alzheimer’s disease, and vascular dementia in developed and developing world regions
149 Table 38: Prevalent Alzheimer’s disease cases in Brazil in the population aged 60+, by geographic level, 2012–30
163 Table 39: Sources used for the epidemiological analysis of Alzheimer’s disease in the US, Japan, and five major EU markets
167 Table 40: Total prevalent cases of Alzheimer’s disease in the US, Japan, and five major EU markets, by country, 2017–37
174 Table 41: Total prevalent cases of mild cognitive impairment due to Alzheimer’s disease in the US, Japan, and five major EU markets, by country, 2017–37
180 Table 42: Key marketed drugs for Alzheimer’s disease
182 Table 43: Aricept drug profile
183 Table 44: Aricept pivotal trial data in Alzheimer’s disease
192 Table 45: Exelon/Exelon Patch drug profile
194 Table 46: Exelon pivotal trial data in Alzheimer’s disease
195 Table 47: Exelon Patch pivotal trial data in Alzheimer’s disease
204 Table 48: Namenda drug profile
205 Table 49: Namenda pivotal trial data in Alzheimer’s disease
213 Table 50: Razadyne drug profile
214 Table 51: Razadyne pivotal trial data in Alzheimer’s disease
224 Table 52: Phase III pipeline products in development for Alzheimer’s disease
230 Table 53: FDA and EMA recommendations for clinical trial endpoints in Alzheimer’s disease
236 Table 54: FDA and EMA recommendations on clinical trial design to demonstrate disease-modifying effects
239 Table 55: Encenicline drug profile
240 Table 56: Encenicline late-phase trials in Alzheimer’s disease
241 Table 57: Idalopirdine drug profile
242 Table 58: Idalopirdine late-phase trials in Alzheimer’s disease
243 Table 59: Solanezumab drug profile
244 Table 60: Solanezumab late-phase trials in Alzheimer’s disease
247 Table 61: LMTX drug profile
249 Table 62: LMTX Phase III data in Alzheimer’s disease
250 Table 63: LMTX Phase III trials in Alzheimer’s disease
260 Table 64: RVT-101 drug profile
261 Table 65: RVT-101 Phase II data in Alzheimer’s disease
264 Table 66: RVT-101 Phase III trials in Alzheimer’s disease
273 Table 67: Aducanumab drug profile
274 Table 68: Aducanumab Phase Ib data in Alzheimer’s disease
276 Table 69: Aducanumab Phase III trials in Alzheimer’s disease
285 Table 70: Azeliragon drug profile
286 Table 71: Azeliragon Phase IIb data in Alzheimer’s disease
288 Table 72: Azeliragon Phase III trials in Alzheimer’s disease
297 Table 73: Crenezumab drug profile
298 Table 74: Crenezumab Phase II data in Alzheimer’s disease
300 Table 75: Crenezumab Phase III trials in Alzheimer’s disease
308 Table 76: Gantenerumab drug profile
309 Table 77: Gantenerumab Phase III data in Alzheimer’s disease
310 Table 78: Gantenerumab Phase III trials in Alzheimer’s disease
317 Table 79: Verubecestat drug profile
318 Table 80: Verubecestat Phase Ib data in Alzheimer’s disease
319 Table 81: Verubecestat Phase II/III trials in Alzheimer’s disease