Stakeholder Insight Parkinson's Disease Evidence of neuroprotection essential to progress treatment dynamics

CHAPTER 1 EXECUTIVE SUMMARY 3
Scope of the analysis 3
Datamonitor insight into the Parkinson's disease market 3
Contributing experts 6
Related reports 6
CHAPTER 2 INTRODUCTION AND SCOPE 8
Coverage of the Stakeholder Insight Survey 8
Disease definition and epidemiology 9
Presentation, diagnosis and comorbidities 9
Pharmacological treatment trends 9
Key prescribing influences 9
Treatment outcomes and surgery 9
Future trends 10
CHAPTER 3 COUNTRY TREATMENT TREES 11
Introduction to treatment trees 11
First-line treatment trees 12
US 12
Japan 13
France 14
Germany 15
Italy 16
Spain 17
UK 18
Second-line treatment trees 19
US 19
Japan 20
France 22
Germany 23
Italy 25
Spain 26
UK 28
CHAPTER 4 EPIDEMIOLOGY AND PATIENT SEGMENTATION 30
Disease definition 31
The etiology of PD is not yet clear 31
Parkinson's disease is typically classified by the Hoehn and Yahr scale 32
Patient population is generally well spread across the three disease severities 33
Epidemiology of Parkinson's disease 36
Parkinson's disease rarely affects adults younger than 50 years of age 37
Prevalence of Parkinson's disease 38
Over 1.4 million individuals across the US, Japan and 5EU are estimated to suffer from PD 39
European and Japanese epidemiology studies 40
Italy 40
UK 41
Japan 42
CHAPTER 5 PRESENTATION, DIAGNOSIS AND COMORBIDITIES 43
Presentation 44
Time to presentation 44
Early symptoms are generally very subtle and often go unnoticed 44
Improving presentation rates 46
Internet and patient advocacy groups are essential awareness drivers 46
Improved education of the public and primary care physicians is needed 47
The four common presentations of PD 48
Tremor 48
Rigidity 49
Akinesia and bradykinesia 49
Postural instability 50
Diagnosis 50
An accurate diagnosis of PD comes from combined neurological, laboratory and imaging evaluations 50
Neurological evaluation of PD 52
Laboratory evaluation of PD 55
Imaging studies for PD 56
Delays in the diagnosis of PD 59
Misdiagnosis is as high as 20-30% in the early stages 59
It takes on average 11 weeks from presentation to a physician to an accurate diagnosis of PD 59
Differential diagnosis to rule out other possible neurological conditions 61
More than half of prevalent early-stage PD patients remain undiagnosed 62
Over 80% of patients are characterized as having either early- or mid-stage PD at diagnosis 65
Comorbidities (non-motor symptoms) of PD 67
Depression is the most common comorbidity at each stage of the disease 68
Depression 69
Dementia 69
Psychosis 70
Sleep disturbances 70
CHAPTER 6 TREATMENT OPTIONS AND GUIDELINES 71
Treatment options 72
Non-pharmacological treatment 72
Non-pharmacological only approaches are largely shelved once mid-stage PD is reached 72
Pharmacological treatment 74
Dopaminergics 74
Dopamine agonists 76
Catechol-O-methyltransferase inhibitors 78
Monoamine oxidase inhibitors 80
Other treatments 81
Surgical treatment 83
Surgery becomes an option when PD symptoms cannot be adequately controlled with medication 83
Deep brain stimulation is now the current standard surgical practice for PD 84
Duodopa pump provides continuous dopaminergic stimulation 86
Treatment guidelines 86
The treatment of PD is a highly individualized process 86
US-guidelines based on AAN recommendations 87
New guidelines issued by the AAN in 2006 are more proscriptive than prescriptive 88
UK-National Institute for Health and Clinical Excellence guidelines 89
Recommended pharmacological therapy in early PD 90
Recommended pharmacotherapy in later PD 92
Guidance on surgery for PD 93
Other guidelines by region 94
CHAPTER 7 PRESCRIBING TRENDS IN PARKINSON'S DISEASE 95
Pharmacological prescribing trends 96
Caveats-prescribing trends 96
Seven major market overview of prescribing trends 96
A greater proportion of patients progress to second-line therapy as the disease severity advances 96
Physician type responsible for initial prescription of PD therapy 97
Neurologists make the majority of initial treatment decisions for PD in the 7MMs 97
Role of pharmacological treatment in the management of PD 99
UK neurologists report waiting the longest period of time before initiating pharmacological therapy once early-stage PD has been diagnosed 99
Pharmacological therapy is not deemed essential in patients characterized as having early-stage PD 102
Pharmacological and non-pharmacological therapy is combined in more than half of all advanced-stage PD patients in Germany and the UK 103
Prescribing trends in early-stage PD 105
The proposed neuroprotective properties of the MAO-B inhibitors and dopamine agonists are still to be proven 105
Age and symptom severity dictates first-line therapy decisions 106
Boehringer Ingelheim's pramipexole (Mirapex) leads the way in first-line early-stage PD management 108
Initiation of pharmacological therapy with levodopa remains high 110
First-line selegiline monotherapy is rarely seen 111
Monotherapy largely dominates early-stage PD management 111
Some 40% of early-stage patients progress to second-line therapy within 20 months 112
60% of early-stage PD patients who progress to second-line therapy have a drug added-on to their first-line regimen 113
Levodopa-carbidopa or levodopa monotherapy are the most commonly added-on products at second-line for early-stage PD 113
Pramipexole and ropinirole are the most common second-line regimens switched to at early-stage 116
Prescribing trends in mid-stage PD 118
Fixed-dose combinations containing levodopa and dopamine agonist therapy make up first-line therapy for mid-stage PD 119
Levodopa-carbidopa therapy is prescribed first-line to a fifth of all mid-stage PD patients in the US 119
Over half of all mid-stage PD patients receive combination therapy 121
50% of mid-stage patients progress to second-line therapy within 2 years 122
Adding-on accounts for the greater proportion of second-line dynamics for mid-stage PD 123
Entacapone is the most commonly added-on therapy at second-line in mid-stage PD 123
Second-line mid-stage PD sees like-for-like dopamine agonist switching and movement towards more complex fixed-dose combination products 125
Prescribing trends in advanced-stage PD 128
Levodopa-carbidopa fixed-dose combination products dominate first-line therapy for advanced PD 129
Monotherapy is rare in advanced-stage PD 130
Over 70% of UK patients progress to second-line therapy for advanced-stage PD 131
Neurologists continue to add-on therapy in the majority of advanced PD cases 132
Amantadine and rasagiline are highly popular add-ons in second-line for advanced PD 133
Apomorphine adding-on is highest in France and Spain 135
Levodopa-benserazide viewed as a second-line alternative to levodopa-carbidopa 138
CHAPTER 8 PRESCRIBING INFLUENCES AND BRAND ASSESSMENT 140
Factors influencing physician decision making 141
Side-effect profile is the number one influential factor 143
Mid- and advanced-stage pharmacotherapy is governed by managing the side effects of levodopa 144
Dopamine agonist side effects are mostly cognitive in nature 145
A drugs ability to reduce OFF periods has a high influence on prescribing decisions 145
The goals of therapy are to reduce OFF periods as much as possible 146
Ability to minimize dyskinesias was rated the most influential attribute in Japan 147
Ability to use as either monotherapy or adjunctive therapy becomes more influential as the disease progresses 148
Ability to delay the use of levodopa therapy influences only initial treatment decisions 149
Ability to enhance the benefit of levodopa therapy has led to the development of a number of products 149
Physician perception of key brands 150
Neurologists in Japan are most satisfied with current therapies 151
Interpreting a brand map 152
Brand comparison shows levodopa remains the "gold standard" symptomatic PD treatment 154
Sinemet (carbidopa-levodopa) 156
Parcopa (carbidopa-levodopa) 159
Madopar (levodopa-benserazide) 160
Stalevo (carbidopa-levodopa-entacapone) 162
The dopamine agonists and now Azilect continue to battle it out for market position 169
Requip (ropinirole) 171
Mirapex (pramipexole) 174
Neupro (rotigotine) 177
Apokyn (apomorphine) 184
Azilect (rasagiline) 188
Comtan (entacapone) 191
CHAPTER 9 TREATMENTS OUTCOMES AND SURGERY 194
Treatment outcomes 195
Only 36% of advanced-stage patients are adequately controlled by pharmacological therapy 195
Intolerable side effects are the key reason for discontinuing or switching treatment 197
Although pill burden affects patient quality of life, it has a low influence on discontinuing or switching therapies 197
Surgical treatment of Parkinson's disease 198
Progression to surgery 198
More than half of the 9% of PD patients who require surgery go on to receive it 198
The invasive nature of surgical techniques limits their use 200
Surgical techniques used 202
Deep Brain Stimulation is by far the most common surgical technique used across the seven major markets 202
Outcome of surgery 204
Over 50% of patients will experience both a reduction in PD symptoms and a reduction in the dose of pharmacological medication with each surgical technique 204
BIBLIOGRAPHY 207
Journal papers 207
Websites 213
APPENDIX A 217
Physician research methodology 217
Physician sample breakdown 217
US 217
Japan 218
France 218
Germany 219
Italy 219
Spain 220
UK 220
Contributing experts 221
APPENDIX B 222
The survey questionnaire 222
Physician's details 222
Screening questions 223
INTRODUCTION 224
Section 1-Patient segmentation and diagnosis of Parkinson's disease 224
Section 2-Treatment of Parkinson's disease 230
Early-stage pharmacological treatment 232
Mid-stage pharmacological treatment 235
Advanced-stage pharmacological treatment 239
Section 3-Key prescribing factors 243
Section 4-Treatment outcomes and Surgery 246
Demographics 249
Disclaimer 251
List of Tables
Table 1: The five stages of PD according to the Hoehn and Yahr scale 33
Table 2: Prevalence of PD across the seven major markets, 2007 39
Table 3: Unified Parkinson's Disease Rating Scale-cognition, behavior and mood 54
Table 4: Proportion of prevalent PD population diagnosed at each disease stage across the seven major markets, 2007 64
Table 5: Options for initial pharmacotherapy in early PD as proposed in NICE guidelines, 2006 91
Table 6: Options for adjuvant pharmacotherapy in later PD as proposed in NICE guidelines, 2006 92
Table 7: Percentage of interviewed neurologists selecting each regimen as a first-line therapy for early-stage PD, 2007 108
Table 8: Early-stage PD second-line therapy patient progression details, 2007 112
Table 9: Percentage of drugs added-on at second-line to the dopamine agonists selected for first-line early-stage PD therapy across the seven major markets, 2007 115
Table 10: Most common selected second-line regimens after switching from first-line dopamine agonist monotherapy for early-stage PD across the seven major markets, 2007 117
Table 11: Percentage of interviewed neurologists selecting each regimen as a first-line therapy for mid-stage PD, 2007 119
Table 12: Percentage of patients receiving each drug regimen as first-line for mid-stage PD, 2007 121
Table 13: Mid-stage PD second-line therapy patient progression details, 2007 122
Table 14: Advanced-stage PD second-line therapy patient progression details, 2007 132
Table 15: Factors that influence drug choice for the management of PD, 2007 142
Table 16: Number and percentage of neurologists able to rate each brand 150
Table 17: Overall performance of each Parkinson's disease drug against six attributes according to interviewed neurologists in the seven major markets, 2007 151
Table 18: The overall performance of each drug against all attributes, and with attribute weightings applied 154
Table 19: Sinemet's attribute scores, by country 158
Table 20: Comparison of Parcopa's and Sinemet's US attribute scores 160
Table 21: Madopar's attribute scores, by country 161
Table 22: Stalevo's attribute scores, by country 164
Table 23: Requip's attribute scores, by country 172
Table 24: Mirapex's attribute scores, by country 176
Table 25: Neupro's attribute scores, by country 179
Table 26: Apokyn's attribute scores, by country 185
Table 27: Treatment-emergent adverse events (incidence ≥10%) and associated rate of discontinuation during open-label long-term use of Apokyn (n=550) 187
Table 28: Azilect's attribute scores, by country 190
Table 29: Comtan's attribute scores, by country 192
Table 30: Reasons for patients discontinuing a therapy/switching to an alternative drug therapy on a scale of 1 to 10, where 1=factor of low influence and 10=factor of high influence, 2006 197
Table 31: US-physician sample breakdown, 2007 217
Table 32: Japan-physician sample breakdown, 2007 218
Table 33: France-physician sample breakdown, 2007 218
Table 34: Germany-physician sample breakdown, 2007 219
Table 35: Italy-physician sample breakdown, 2007 219
Table 36: Spain-physician sample breakdown, 2007 220
Table 37: UK-physician sample breakdown, 2007 220
List of Figures
Figure 1: Diagrammatic overview of the coverage of the Stakeholder Insight: Parkinson's Disease survey, 2007 8
Figure 2: Parkinson's disease treatment tree split by disease severity in the US, 2007 12
Figure 3: Parkinson's disease treatment tree split by disease severity in Japan, 2007 13
Figure 4: Parkinson's disease treatment tree split by disease severity in France, 2007 14