Table of Contents

Stakeholder Perspectives: Mild Cognitive Impairment and Dementia - Aricept in race to pioneer unexplored markets - Drug manufacturers look beyond mild-to-moderate Alzheimer's disease

Product Code: DMHC1924

Publication Date: 18-Aug-2003

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Overview

Introduction

While the mild to moderate Alzheimer’s disease (AD) market grew strongly over 2002 to exceed $1.5 billion, drug manufacturers are now recognizing opportunities in other areas of the dementia population. Of particular interest is the treatment of mild cognitive impairment (MCI), treatment of severe AD, and treatment of vascular dementia.

Scope

· Epidemiology: including prevalence split by the seven major markets, diagnosis rates, and treatment rates

· Analysis of unmet needs as identified by opinion leaders

· Discussion of current drug treatments

· Analysis of drugs in late stage development for these areas, including Aricept, Exelon, Reminyl and memantine

Report Highlights

There are no approved drugs for MCI, VaD with only memantine approved for severe AD in the EU. Companies currently manufacturing of AD products, Aricept, Exelon and Reminyl are expected to file NDA’s for treatment of MCI during 2004.

Despite Aricept’s failure to gain FDA approval for VaD in July 2003, Datamonitor predicts it will be approved during 2005 and will experience the benefits of first to market status.

Memantine is currently the only treatment approved for sever AD in the EU, and is expected to be launched in the US during 2004. Datamonitor predicts strong uptake in this niche market with see sales nearing blockbuster figures over the next 8 years.

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Table of Contents

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CHAPTER 1 EXECUTIVE SUMMARY	3
1.1 Scope	3
1.2 Datamonitor insight into the MCI and dementia markets	3
MCI, the prodromal disease of AD, affects nearly 15 million people in the seven major markets. There are no approved drugs for MCI, although companies currently manufacturing AD products, Aricept (donepezil), Exelon (rivastigmine) and Reminyl (galantamine) are expected to file NDA’s during 2004.	4
VaD is the second most common cause of dementia and affects nearly four million people in the seven major markets, although opinion leaders expect the figure to be significantly higher as only 15% of patients are accurately diagnosed. There are currently no drugs approved for VaD, and Pfizer/Eisai’s Aricept, believed to have the best chance of first-to-market status, failed to gain FDA approval in July 2003.	5
Severe AD represents 20% of the total AD population, accounting for nearly one million people in the US alone. Memantine is currently the only treatment approved for severe AD in the EU, and is currently awaiting FDA approval in the US. Forest, which is memantine’s US marketing company, has an additional NMDA antagonist, neramexane, in Phase III development. Datamonitor believes neramexane will help reduce the impact to Forest’s share price if memantine fails to launch in the US.	5
1.3 Key metrics	6
CHAPTER 2 MILD COGNITIVE IMPAIRMENT	8
Disease overview	9
Symptomology	9
Predictive factors of conversion to AD	10
Diagnosis	11
2.1 Epidemiology	12
Prevalence	12
Diagnosis rates	13
2.2 Unmet needs	14
Delayed progression to AD	14
Approval of disease modifying drugs	15
Drugs that improve memory	15
More accurate diagnosis	15
Non-drug treatments	16
2.3 Pharmacotherapy	16
Current treatment	16
2.4 Key late stage clinical trial analysis	18
Acetylcholinesterase inhibitors	19
Aricept	20
Exelon	24
Reminyl	26
2.5 Drugs in Phase I & II trials for MCI	28
Ampalex	28
2.6 Summary of trials	30
2.7 Commercial perspectives	30
The need for improved early and accurate diagnosis	30
Reformulations	32
Potential for disease modifying therapy	32
Standardized clinical trial design	33
CHAPTER 3 VASCULAR DEMENTIA	35
3.1 Introduction	36
Disease overview	36
Symptomology	36
Predictive factors	37
Diagnosis	37
3.2 Epidemiology	38
Prevalence	38
Diagnosis rates	39
3.3 Unmet needs	40
Improved prevention of cardiovascular disease	41
Improved diagnosis of people at risk	41
Increased awareness	41
Approval of symptomatic drugs	41
3.4 Pharmacotherapy	42
Current treatment	42
3.5 Key clinical trial analysis	43
Late stage R&D pipeline overview	43
Aricept	45
Reminyl	47
Exelon	50
Memantine	51
Drugs in Phase I & II trials for VaD	54
3.6 Summary of trials	54
3.7 Commercial perspectives	55
Future of VaD therapy	55
Implications of Aricept trial failure	55
Stroke prevention	56
CHAPTER 4 SEVERE ALZHEIMER’S DISEASE	57
4.1 Introduction	58
Disease overview	58
Symptomology	58
Diagnosis	58
4.2 Epidemiology	59
Prevalence	59
Diagnosis rates	60
Unmet needs	60
4.3 Pharmacotherapy	61
Current treatment	61
Memantine	61
4.4 Key clinical trial analysis	63
Late stage R&D pipeline overview	63
Memantine	65
Neramexane	68
4.5 Summary of trials	68
4.6 Commercial perspectives	68
Approval of memantine	68
Off-label use of AChEIs	69
Drug approval and reimbursement	69
CHAPTER 5 APPENDIX A	71
5.1 Contributing experts	71
5.2 List of tables	71
5.3 List of figures	71
5.4 Bibliography	71
References	71
Websites	75
5.5 R&D research methodology	75
Introduction	75
Hypothesis formulation	76
Hypothesis testing	76
Data verification and quality control	77
5.6 Introduction to Datamonitor Healthcare forecasting	77
5.7 Current drug forecast methodology	78
Methodology	78
Market events	80
Validation	81
5.8 Pipeline drug forecast methodology	82
Predicting initial market share	83
Forecasting future growth	84
Influencing factors	84
CHAPTER 6 APPENDIX B: ABOUT DATAMONITOR	85
6.1 About Datamonitor	85
About Datamonitor Healthcare	85
6.2 Datamonitor Healthcare’s therapy area capabilities	86
About Disease analysis team	87
Datamonitor Healthcare’s Consulting expertise	88
Key therapy team members	89
Disclaimer	93
List of Tables
Table 1: Prevalence of MCI, VaD and severe AD in the seven major markets, 2003	6
Table 2: Diagnostic criteria for MCI	11
Table 3: Prevalence of MCI in the seven major markets, 2003	12
Table 4: MCI drugs in Phase III clinical trials	19
Table 5: VaD risk factors	37
Table 6: The prevalence of VaD in the seven major markets, 2003	39
Table 7: VaD therapeutics in Phase III clinical trials	44
Table 8: Prevalence of severe AD in the seven major markets, 2003	59
Table 9: Severe AD therapeutics in Phase III clinical trials	64
List of Figures
Figure 1: Memory function and general cognition in MCI, AD and normal subjects	10
Figure 2: Unmet needs in the treatment of MCI, 2003	14
Figure 3: Key factors in the market potential of Aricept	22
Figure 4: Key factors in the market potential of Exelon	25
Figure 5: Key factors in the market potential of Reminyl	27
Figure 6: Key factors in the market potential of Ampalex	29
Figure 7: Unmet needs in the treatment of VaD, 2003	40
Figure 8: Drugs used to treat comorbidities of VaD	43
Figure 9: Key factors in the market potential of Aricept	46
Figure 10: Key factors in the market potential of Reminyl	49
Figure 11: Key factors in the market potential of Exelon	51
Figure 12: Key factors in the market potential of memantine	53
Figure 13: Unmet needs in the treatment of severe AD, 2003	60
Figure 14: Key factors in the market potential of memantine	66
Figure 15: Market events affecting baseline product forecasts	80
Figure 16: Algorithm depicting key constituent variables upon which drug revenues depend	81
Figure 17: Overview of Datamonitor Healthcare’s forecasting approach for pipeline drugs	82
Figure 18: Datamonitor’s Healthcare Consultancy	88
Figure 19: Therapeutic Consulting capabilities	89

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