Alzheimer's Disease - Prescribing trends indicate that neurologists are not adhering to guidelines
Scope
Report Highlights
Reasons to Purchase
Table of Contents
- ABOUT DATAMONITOR HEALTHCARE - page 2
- CHAPTER 1 EXECUTIVE SUMMARY - page 3
- Scope of the analysis - page 3
- Datamonitor insight into the Alzheimer's disease market - page 4
- CHAPTER 2 INTRODUCTION AND SCOPE - page 16
- Coverage of the Stakeholder Insight Survey - page 16
- Disease definition & epidemiology - page 16
- Diagnosis - page 16
- Key prescribing influences - page 16
- Coverage of the Stakeholder Insight Survey - page 16
- CHAPTER 3 COUNTRY TREATMENT TREES - page 18
- Country treatment trees - page 18
- CHAPTER 4 EPIDEMIOLOGY AND PATIENT SEGMENTATION - page 26
- Definition of Alzheimer's disease - page 26
- Etiology - page 26
- Beta-amyloid hypothesis - page 26
- Tau neurofibrillary tangles - page 27
- Neuronal death caused by beta-amyloid deposition and neurofibrillary tangles - page 28
- Etiology - page 26
- Prevalence of Alzheimer's disease and other dementias - page 29
- Literature-reported Alzheimer's prevalence rates - page 29
- US AD population - page 29
- EU5 and Japan AD populations - page 29
- Comparison with other reported AD prevalence rates - page 32
- Datamonitor survey reported Alzheimer's disease prevalence rates - page 34
- Factors influencing prevalence - page 35
- Age and gender - page 35
- Patients most frequently presented for the first time in the 70-79 age group - page 35
- Genetics - page 37
- Prevalence rates of Mild Cognitive Impairment and other dementias - page 38
- Neurologists reported similar prevalence rates of Mild Cognitive Impairment and Alzheimer's disease - page 38
- Mild cognitive impairment (MCI) may be a precursor to AD - page 38
- Off-label prescribing for MCI constitutes approximately 6% of acetyl cholinesterase inhibitors sales in the seven major markets - page 40
- Progression of MCI to Alzheimer's disease - page 42
- Literature-reported Alzheimer's prevalence rates - page 29
- Segmentation of Alzheimer's disease - page 42
- Clinical features of Alzheimer's disease severity subtypes - page 42
- Mild AD affects memory, language and reasoning - page 43
- Moderate AD demonstrates more pronounced symptoms - page 43
- Severe AD leaves patients completely dependent - page 44
- Prescribers may not regard the segmentation of AD into severities as clinically significant - page 44
- Patients are generally categorized as suffering from moderate AD for the longest period of the disease progression - page 44
- Clinical definition and features of each AD severity - page 45
- Prevalence of Alzheimer's disease severity subtypes - page 47
- Clinical features of Alzheimer's disease severity subtypes - page 42
- Co-morbidities - page 48
- A large proportion of the AD population suffer from co-morbidities - page 48
- Treating depression improves quality of life and behavior - page 49
- Treatment of agitation, aggression and psychotic symptoms is limited by side effects - page 49
- Anxiety is treated using antidepressants and benzodiazepines - page 51
- Treatment of sleep disturbances is a difficult balance of sedation - page 51
- Broad symptomatology provides commercial opportunity - page 51
- A large proportion of the AD population suffer from co-morbidities - page 48
- Definition of Alzheimer's disease - page 26
- CHAPTER 5 DIAGNOSIS AND TREATMENT OPTIONS - page 53
- Presentation and diagnosis - page 53
- Diagnosis techniques - many hopes on the horizon, but current practices have not developed much in the last 100 years - page 53
- Diagnostic guidelines for AD are provided by multiple sources - page 54
- Severity of AD is often assessed using symptomatic subscales - page 55
- An holistic view of AD progression is lacking - page 56
- Time to presentation - page 56
- Time to presentation may seem long, but KOLs were unconcerned - page 57
- It is in pharmaceutical companies' interests to decrease this time by increasing awareness - page 58
- Significant reduction in time to presentation only possible following development of more advanced diagnostic tools - page 59
- The future - biomarkers - page 59
- Time to correct diagnosis - page 62
- Treatment options - page 65
- Non-pharmacological treatment is still a commonly used option for AD therapy - page 65
- Pharmacological treatment - page 66
- Acetylcholinesterase inhibitors - page 66
- NMDA receptor antagonist: Memantine (Namenda/Ebixa/Axura) - page 67
- Non-pharmacological treatment - page 68
- Treatment guidelines - page 69
- UK - National Institute of Clinical Excellence (NICE) guidelines - page 69
- NICE guidelines for AD - page 69
- NICE guidelines are for the UK NHS only, but may have further reaching implications - page 70
- How could NICE guidelines directly impact AD drug sales in the UK? - page 71
- Treatment of cognitive symptoms with AChEIs only recommended for moderate severity AD patients - page 72
- It is still advised that mild and severe severity AD patients with non-cognitive symptoms receive AChEIs - page 74
- Choice of AChEIs - page 75
- If cost-benefit analysis had been conducted on the actual cost paid by PCTs, the AChEIs could be cost-effective - page 75
- NICE only considers the direct cost to the NHS, if costs to individuals and social services had been appreciated, the cost-benefit balance may have been different - page 76
- Memantine not recommended for AD treatment of any severity - page 76
- An evaluation of AChEI/memantine combination therapy would more closely reflect treatment regimes - page 77
- NICE recommend continuation of therapy for patients currently receiving treatment - page 77
- Datamonitor's view on the direct effect of these NICE guidelines on sales revenue - page 78
- Can an estimate of future prescribing trends post-NICE recommendations be made from past prescribing? - page 79
- Germany - Institute for Quality and Efficiency (IQWiG) - page 80
- American Academy of Neurology guidelines - page 80
- Other guidelines in the seven major market - page 82
- UK - National Institute of Clinical Excellence (NICE) guidelines - page 69
- Referral patterns - page 83
- Presentation and diagnosis - page 53
- CHAPTER 6 PRESCRIBING TRENDS AND INFLUENCING FACTORS - page 84
- Prescribing trends - page 84
- Prescribing trends caveats - page 84
- Role of pharmacological treatment in the management of AD - page 85
- Progression from first- to second-line therapy consistent across disease severity - page 85
- Higher percentage of pharmacological treatment for severe AD patients than mild AD patients would seem contradictory to clinical benefit - page 86
- Pharmacological treatment of severe AD patients particularly high in relation to mild AD patients in the UK - page 87
- Pharmacological treatment of moderate AD patients higher in the US than the EU5 - page 87
- Companies marketing AD drugs should concentrate resources on the treatment of mild AD patients in the six major markets outside of the US - page 87
- Seven major market overview of prescribing trends for AD - page 89
- Overview of treatment paradigms for AD patients - page 89
- Eisai's and Pfizer's donepezil (Aricept) is the clear market leader in AD treatment - page 89
- What is first- and second-line AD treatment? - page 90
- Memantine is used more frequently in combination with an AChEI than as a monotherapy in moderate and severe AD patients - page 91
- Use of combination therapy as a first-line treatment increases through the disease progression - page 92
- First- to second-line progression - page 93
- Approximately one-quarter of pharmacologically treated patients move to second-line treatment when first-line treatment has failed - page 93
- Second-line therapy consists of either adding memantine to the treatment regime, or switching patients to another AChEI - page 93
- Increased use of AChEI + memantine combination treatment in second-line therapy - page 94
- Neurologists not prescribing combination therapy first-line for mild severity AD patients, prescribe it as a second-line therapy - page 95
- More mild severity AD patients treated by neurologists that do not prescribe AChEI and memantine combination therapy move to second-line therapy - page 96
- Neurologists that do not prescribe mild severity AD patients combination therapy first-line, do prescribe this treatment regime for moderate and severe patients - page 98
- Lundbeck/Forest should attempt to stimulate prescribing of memantine first-line, especially in mild AD patients - page 99
- Off-label prescribing in the AD market - page 99
- Neurologists reported that off-label prescribing of the AChEIs and memantine represents approximately one-fifth of total prescribing - page 99
- Beyond other unlicensed disease severities, what are AChEIs and memantine used for off-label? - page 102
- Factors influencing physician decision making - page 103
- Neurologists report efficacy based factors are the primary considerations when prescribing AD drugs - page 103
- Symptomatic improvement is still a high priority - page 103
- Neurologists would welcome a new non-disease modifying drug if it was differentiated from the AChEIs - page 104
- Neurologists regard the introduction of a disease modifying drug as critical in the longer term - page 105
- Side-effect profile is the most important non-efficacy related factor considered by neurologists when prescribing AD drugs - page 107
- Reimbursement status, formulary inclusion and cost effectiveness are the least considered factors by neurologists when prescribing AD drugs - page 107
- Neurologists report efficacy based factors are the primary considerations when prescribing AD drugs - page 103
- Scenarios for future AD treatment paradigms, patient prognosis and the AChEI market - page 108
- Datamonitor believe that the introduction of disease modifying drugs will not threaten AChEI sales - page 108
- Diagram A - Untreated AD patient - page 108
- Diagram B - AD patient prescribed an AChEI (and/or memantine) - page 108
- Diagram C - AD patient prescribed ideal disease slowing drug - page 109
- Diagram D - AD patient prescribed efficacious disease slowing drug - page 109
- Diagram E - AD patient prescribed ideal disease slowing drug and cognitive enhancer (e.g. AChEI) - page 109
- Diagram F - AD patient prescribed efficacious disease modifying drug and cognitive enhancer - page 110
- Diagram G - AD patient prescribed ideal disease slowing/disease modifying drug diagnosed before cognitive decline with a biomarker - page 111
- Diagram H - AD patient prescribed ideal disease modifying drug - page 111
- Datamonitor believe that the introduction of disease modifying drugs will not threaten AChEI sales - page 108
- Late-stage disease modifying drugs aim to attenuate the production of 'toxic' beta-amyloid - page 115
- Alzhemed - page 115
- Clinical trials investigating the efficacy of Alzhemed - page 116
- Flurizan - page 119
- Phase III trials investigating Flurizan currently underway - page 119
- Phase II studies - page 120
- Alzhemed - page 115
- Neurologists perception of marketed and pipeline drugs - page 121
- Datamonitor has used a brand map to show the significance of neurologists' perception of the marketed and pipeline drugs - page 121
- Interpreting Datamonitor's AD brand map - page 121
- Datamonitor's brand map shows a clear differentiation between the three classes of AD drug - page 123
- Symptomatic improvement characteristic defines the AChEI class of drug - page 124
- Memantine's side-effect profile differentiates it from other classes of AD drugs - page 124
- Neurologists believe that the beta-amyloid modifying pipeline drugs will prove to be disease modifying by slowing disease progression - page 125
- Indication expansion - page 125
- Donepezil (Aricept) for severe Alzheimer's patients - page 125
- Due to off-label prescribing, the severe severity AD market may already be saturated - page 127
- Donepezil's (Aricept) number one position in the AD market will be secured following this license - page 129
- Donepezil (Aricept) for severe Alzheimer's patients - page 125
- Reformulation strategies - page 130
- Launch of liquid donepezil (Aricept) - page 130
- Generic incursion - page 132
- Neurologists' perceptions of generic uptake - page 132
- Reduced cost, increased use? - page 133
- Prescribing trends - page 84
- CHAPTER 7 IMPROVING TREATMENT OUTCOMES - page 136
- Treatment outcomes - page 136
- Patient response to current treatment is modest - page 136
- Reason for discontinuing therapy - page 138
- Lack of efficacy and intolerable side effects are the leading reasons for treatment discontinuation - page 138
- Unmet needs - page 139
- Overview of neurologist weighted unmet needs - page 139
- Improved efficacy of treatment remains the most important clinical unmet need - page 140
- Improved side effect profile of treatments is imperative given the overall health of the many AD patients - page 142
- Cost is an issue because of a general move towards pharmacoeconomic evaluations and the potential arrival of new treatments - page 145
- Treatment outcomes - page 136
- BIBLIOGRAPHY - page 147
- Journals - page 147
- Websites - page 152
- Datamonitor reports - page 154
- APPENDIX A - page 155
- Physician research methodology - page 155
- Physician sample breakdown - page 155
- Contributing experts - page 155
- Physician research methodology - page 155
- APPENDIX B - page 157
- The survey questionnaire - page 157
- Epidemiology, presentation and diagnosis of Alzheimer's disease - page 157
- Treatment of Alzheimer's disease - page 160
- Treatment of mild Alzheimer's disease - page 161
- Treatment of moderate Alzheimer's disease - page 163
- Treatment of severe Alzheimer's disease - page 165
- Current and future treatment of Alzheimer's disease - page 168
- Key prescribing factors - page 172
- Unmet Needs - page 178
- Disclaimer - page 179
- The survey questionnaire - page 157
- List of Tables
- Table 1: Prevalence of Alzheimer's disease by gender and age - page 31
- Table 2: Population size and prevalence rate of Alzheimer's disease across the seven major markets, 2006 - page 32
- Table 3: Survey-reported prevalence of AD among the adult population in the seven major markets, 2006 - page 34
- Table 4: Common clinical features in Alzheimer's disease by stage - page 46
- Table 5: DSM-IV criteria for Alzheimer's disease type dementia - page 55
- Table 6: IMS reported sales in the seven major markets ($), 2005 - page 90
- Table 7: Off-label prescribing as a total of pharmacologically treated patients in the specified disease severity, 2006 - page 101
- Table 8: Percentage of additional severe severity AD patients prescribed donepezil first-line following license for severe AD therapy, 2006 - page 128
- Table 9: Expiry dates and patents for marketed AChEIs - page 133
- Table 10: Comparison of AChEI treatment response outcomes, according to a meta-analysis of clinical trials, 2006 - page 136
- Table 11: Comparison of adverse events and discontinuation outcomes, according to a meta analysis of AChEI clinical trials - page 139
- Table 12: Reported adverse events of donepezil versus placebo in clinical trials - page 142
- Table 13: Adverse events reported in controlled clinical trials in at least 2% of patients receiving memantine and at a higher frequency than placebo-treated patients - page 144
- Table 14: Annual cost comparison of approved AD drugs in the US versus the UK, 2006 - page 145
- Table 15: AD survey sample breakdown, 2006 - page 155
- Table 16: Survey question 1. - page 157
- Table 17: Survey question 30. - page 171
- Table 18: Survey question 31 - page 171
- List of Figures
- Figure 1: Country Alzheimer's disease treatment tree: US - page 19
- Figure 2: Country Alzheimer's disease treatment tree: France - page 20
- Figure 3: Country Alzheimer's disease treatment tree: Germany - page 21
- Figure 4: Country Alzheimer's disease treatment tree: Italy - page 22
- Figure 5: Country Alzheimer's disease treatment tree: Spain - page 23
- Figure 6: Country Alzheimer's disease treatment tree: UK - page 24
- Figure 7: Country Alzheimer's disease treatment tree: Japan - page 25
- Figure 8: Amiloydogenic pathway: Formation of toxic beta-amyloid - page 27
- Figure 9: Overview of Datamonitor's AD population size methodology - page 30
- Figure 10: US population by age and gender, 2005 - page 31
- Figure 11: Comparison of data from individual AD incidence studies - page 33
- Figure 12: Breakdown of patients first presenting with AD by age group, 2006 - page 36
- Figure 13: Comparison of the prevalence rate for dementia related diseases, 2006 - page 38
- Figure 14: Percentage of MCI patients progressing to AD in any given year - page 42
- Figure 15: Percentage of patients with each severity of AD, 2006 - page 47
- Figure 16: Percentage of AD patients suffering from each co-morbidity, 2006 - page 48
- Figure 17: Number of months from the onset of symptoms to initial presentation to a clinician, 2006 - page 56
- Figure 18: Number of months from initial presentation to an accurate diagnosis, 2006 - page 62
- Figure 19: Mean percentage of pharmacological and non-pharmacological therapy across the seven major markets, 2006 - page 65
- Figure 20: Patient referral pathway and prescribing physician type - page 83
- Figure 21: Role of pharmacological treatment in AD management, 2006 - page 85
- Figure 22: Percentage of patients receiving pharmacological therapy for AD across the seven major markets, 2006 - page 86
- Figure 23: First-line treatment regimes in the seven major markets, 2006 - page 89
- Figure 24: Total number of patients suffering from each disease severity and the type of treatment paradigm administered first-line across the seven major markets, 2006 - page 92
- Figure 25: Second-line treatment paradigms in the seven major markets, 2006 - page 93
- Figure 26: Comparison of AChEI + memantine combination therapy as a first-line and second-line treatment, 2006 - page 94
- Figure 27: Percentage of mild AD patients prescribed AChEI or AChEI + memantine combination therapy as first- and second-line treatment in the US and EU5, 2006 - page 95
- Figure 28: Percentage of mild AD patients moving from first- to second-line therapy, 2006 - page 97
- Figure 29: Percentage of patients prescribed first-line AChEI and memantine combination therapy across disease severities in the US and EU5, 2006 - page 98
- Figure 30: Percentage of prescribing for off-label indications, 2006 - page 99
- Figure 31: Off-label prescribing of AChEIs and memantine in non-AD patients, 2006 - page 102
- Figure 32: Factors influencing choice of AD pharmacological treatment in the seven major markets, 2006 - page 103
- Figure 33: Cognitive decline in treated and non-treated AD patients (1) - page 113
- Figure 34: Cognitive decline in treated and non-treated AD patients (2) - page 114
- Figure 35: Brand map of marketed and pipeline AD drugs - page 123
- Figure 36: Percentage of severe severity AD patients which would be prescribed donepezil following license for severe therapy, 2006 - page 127
- Figure 37: Switching from donepezil tablets to oral disintegrating tablets, 2006 - page 130
- Figure 38: Neurologists' opinions on the impact of generics on prescribing trends for AD patients, 2006 - page 132
- Figure 39: Neurologist rated reasons for discontinuation of therapy in the seven major markets, 2006 - page 138
- Figure 40: Neurologist weighted unmet needs, 2006 - page 140
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