Summary
Parkinson's Disease (PD) is a progressive, chronic neurodegenerative condition, which is currently incurable. It is associated with old age, and characterized by the loss of neurons in the substantia nigra region of the brain. The global Parkinson's Disease (PD) prevalence was estimated at 16.1 million in 2011, and after Alzheimer's disease it is the second most common neurodegenerative disease worldwide.
Parkinson's Disease (PD) is a progressive disease and, although not fatal, it can develop severe symptoms and complications that significantly impact upon the patient's quality of life. Symptoms for each stage can be categorized into early, moderate and advanced stages. Major motor symptoms of Parkinson's Disease (PD) include tremors and difficulty walking. Parkinson's Disease (PD) also gives rise to non-motor symptoms, such as dementia, depression, hallucinations and loss of taste and smell.
There are several different drug classes available to relieve Parkinson's Disease (PD) symptoms. The aim is for treatments to increase dopamine levels, which is substantially diminished in brains affected by Parkinson's Disease (PD). The most common therapies include levodopa, dopamine agonists and Monoamine Oxidase-B (MAO-B) inhibitors, with the choice of therapies dependent on patient symptoms and lifestyle. As the disease develops, the medication will need to be taken more strictly, due to the effect of drugs wearing off (known as off- time), which causes symptoms to return before the next dose.
With the current marketed drugs focusing primarily on symptomatic relief, Parkinson's Disease (PD) remains incurable, with a huge unmet need for disease-modifying therapies. However, due to the lack of clearly established clinical trial methodologies, replication of the benefits demonstrated by neuroprotective agents in the laboratory to human trials has proved challenging. More importantly, due to an incomplete understanding of the underlying mechanisms that cause the disease, a viable therapeutic target to halt or slow disease progression is currently not in scope, which limits the effectiveness of current product development programs.
Scope
- A brief introduction to Parkinson’s Disease (PD), including pathogenesis, disease staging, diagnosis and treatment algorithms
- Comprehensive analysis of the drugs available for the treatment of PD, covering their safety, efficacy, treatment patterns, and strengths/weaknesses, as well as a heat map comparing drugs in terms of safety and efficacy
- Comprehensive analysis of the pipeline for Parkinson’s Disease (PD) therapies, including individual analysis of a number of late-stage pipeline drugs that are likely to enter the market in the forecast period, on the basis of Phase distribution, molecule type and molecular target
- Additional thorough analysis of pipeline drug clinical trials by Phase, molecule type, trial size, trial duration, and program failure rate for each molecule type and mechanism of action
- Multi-scenario market forecast data to 2021, taking into account how it will be affected by the introduction of new drugs, the expiry of key patents on current drugs, and changes in disease epidemiology across the key developed markets of the US, Canada, Japan, Germany, the UK, France, Italy and Spain
- Discussion of the drivers of and barriers to market growth
- Discussion of the licensing and co-development deals landscape in Parkinson’s Disease (PD), by stage of development, molecule type and mechanism of action, as well as analysis of both licensing and co-development deals by year, and network maps of licensing and co-development deals
Reasons to buy
- Understand the different levels of Parkinson’s Disease (PD) therapy from early-stage to advanced
- Understand the vast scope of the pipeline, including which molecule types and mechanisms of action are prominent
- Observe the trends in clinical trial duration and size among clinical Phases and molecule types, and use the clinical trial failure rate analysis to assess the risk profiles of current and/or forthcoming developmental programs for Parkinson’s Disease (PD) therapeutics
- Observe the trends in clinical trial duration and size among clinical Phases, between molecule types and mechanisms of action, and use the clinical trial failure rate analysis to assess the risk profiles of current and/or future developmental programs for Parkinson’s Disease (PD) therapeutics
- Assess the potential clinical and commercial impact of current late-stage pipeline molecules on the Parkinson’s Disease (PD) therapeutics market
'
1 Table of Contents
1 Table of Contents 5
1.1 List of Tables 7
1.2 List of Figures 7
2 Introduction 9
2.1 Disease Introduction 9
2.2 Symptoms 9
2.3 Etiology 10
2.3.1 Genetic Factors 10
2.3.2 Environmental Factors 11
2.3.3 Aging 11
2.4 Pathophysiology 12
2.5 Epidemiology 13
2.6 Disease Stages 14
2.7 Co-morbidities and Complications 15
2.8 Diagnosis 15
2.9 Assessment of Disease Severity 16
2.9.1 Hoehn and Yahr scale 16
2.9.2 Unified Parkinson’s Disease Rating Scale 16
2.10 Treatment 17
2.10.1 Pharmacological Therapies 18
2.10.2 Non-pharmacological Treatments 20
2.11 Treatment Algorithm 21
2.11.1 Early Parkinson’s Disease 21
2.11.2 Advanced Parkinson’s Disease 22
3 Marketed Products 25
3.1 Overview 25
3.1.1 Dopamine Replacement Therapies 25
3.1.2 MAO-B Inhibitors 28
3.1.3 Dopamine Agonists 30
3.1.4 COMT Inhibitors 35
3.1.5 Other Drugs Targeting Non-motor Symptoms of PD 39
3.2 Comparative Efficacy and Safety 40
4 Pipeline for Parkinson’s Disease 44
4.1 Overview 44
4.2 Pipeline Distribution by Mechanism of Action/Molecular Target 46
4.3 Clinical Trials 49
4.3.1 Failure Rate 49
4.3.2 Clinical Trial Duration 51
4.3.3 Clinical Trial Size 53
4.3.4 Comparison of Average Trial Metrics by Phase and Mechanism of Action 55
4.4 Promising Pipeline Molecules 56
4.4.1 Opicapone – Bial 56
4.4.2 Nuplazid (pimavanserin) – Acadia Pharmaceuticals 58
4.4.3 Nurelin (Amantadine Hydrochloride Extended-Release) – Adamas Pharmaceuticals 59
4.4.4 Tozadenant – Biotie Therapies 60
4.4.5 APL-130277 (apomorphine hydrochloride) – Cynapsus Therapeutics 61
4.4.6 P2B001 (pramipexole dihydrochloride + rasagiline mesylate) – Pharma Two B 63
4.4.7 DM-1992 (levodopa + carbidopa extended release) – Depomed 63
4.4.8 CVT-301 (levodopa) – Acorda Therapeutics 65
4.4.9 Dipraglurant Immediate-Release– Addex Therapeutics 65
4.4.10 Accordion Pill (levodopa and carbidopa) – Intec Pharma 66
4.4.11 ND-0612L (levodopa and carbidopa) – NeuroDerm 67
4.5 Heatmaps of Safety and Efficacy for Parkinson’s Disease Pipeline and Marketed Products 69
4.6 Pipeline Product Heat Map and Product Competitiveness Framework 73
5 Market Forecast to 2021 74
5.1 Geographical Markets 74
5.1.1 Global Market 74
5.1.2 North America 76
5.1.3 Top Five European Markets 79
5.1.4 Japan 84
5.2 Drivers and Barriers 85
5.2.1 Drivers 85
5.2.2 Barriers 86
6 Strategic Consolidations 88
6.1 Major Co-Development Deals 88
6.1.1 TechnoPhage Enters into Co-Development Agreement with University of Macau 90
6.1.2 Dainippon Sumitomo Pharma Enters into Research Agreement with CiRA and Hitachi 90
6.1.3 MJFF Enters into Agreement with Prothena 90
6.1.4 Ubiquigent Enters into Co-Development Agreement with UbiQ 91
6.1.5 23andMe Partners with Genentech 91
6.2 Major Licensing Deals 91
6.2.1 Cephalon Enters Into Licensing Agreement With Mesoblast For Regenerative Medicine 93
6.2.2 Dexcel Pharma Enters into Licensing Agreement with Ramot at Tel Aviv University 94
6.2.3 Neuropore Therapies Enters into Licensing Agreement with UCB 94
6.2.4 Catalent Pharma Solutions Enters into Licensing Agreement with Sellas Life Sciences 94
6.2.5 MedGenesis Therapeutix Enters into Licensing Agreement with Pfizer 95
7 Appendix 96
7.1 All Pipeline Drugs by Stage of Development 96
7.1.1 Discovery 96
7.1.2 Preclinical 100
7.1.3 IND/CTA-filed 112
7.1.4 Phase I 113
7.1.5 Phase II 115
7.1.6 Phase III 117
7.1.7 Pre-registration 118
7.2 Market Forecasts to 2021 118
7.2.1 Global 118
7.2.2 US 118
7.2.3 Canada 119
7.2.4 UK 119
7.2.5 France 119
7.2.6 Germany 120
7.2.7 Italy 120
7.2.8 Spain 120
7.2.9 Japan 121
7.3 References 121
7.4 Abbreviations 129
7.5 Research Methodology 132
7.6 Secondary Research 133
7.7 Marketed Product Profiles 133
7.8 Late-Stage Pipeline Candidates 133
7.9 Comparative Efficacy and Safety Heat Map for Marketed and Pipeline Products 134
7.10 Product Competitiveness Framework 134
7.11 Pipeline Analysis 134
7.11.1 Overall Pipeline 134
7.11.2 Clinical Trials 134
7.11.3 Failure Rate 134
7.11.4 Clinical Trial Size 135
7.11.5 Clinical Trial Duration 135
7.11.6 Forecasting Model 135
7.12 Deals Data Analysis 136
7.13 Expert Panel Validation 136
7.14 Contact Us 136
7.15 Disclaimer 136
1.1 List of Tables
Table 1: Gene Mutations Related to Parkinson’s Disease and Corresponding Clinical Phenotypes 12
Table 2: Hoehn and Yahr Scale and the Definition of Disability Stages 16
Table 3: Unified Parkinson’s Disease Rating Scale 16
Table 4: All Pipeline Products by Phase, Discovery 96
Table 5: All Pipeline Products by Phase, Preclinical 100
Table 6: All Pipeline Products by Phase, IND/CTA-filed 112
Table 7: All Pipeline Products by Phase, Phase I 113
Table 8: All Pipeline Products by Phase, Phase II 115
Table 9: All Pipeline Products by Phase, Phase III 117
Table 10: All Pipeline Products by Phase, Phase III and Pre-registration 118
Table 11: Global, Parkinson's Disease Market Forecast, 2014–2021 118
Table 12: US, Parkinson's Disease Market Forecast, 2014–2021 118
Table 13: Canada, Parkinson's Disease Market Forecast, 2014–2021 119
Table 14: UK, Parkinson's Disease Market Forecast, 2014–2021 119
Table 15: France, Parkinson's Disease Market Forecast, 2014–2021 119
Table 16: Germany, Parkinson's Disease Market Forecast, 2014–2021 120
Table 17: Italy, Parkinson's Disease Market Forecast, 2014–2021 120
Table 18 : Spain, Parkinson's Disease Market Forecast, 2014–2021 120
Table 19: Japan, Parkinson's Disease Market Forecast, 2014–2021 121
1.2 List of Figures
Figure 1: Overview of the Basal Ganglia in the Normal State and Parkinson’s Disease State 13
Figure 2: Parkinson’s Disease Market, Global, Efficacy Heat Map for Marketed Products (Part 1) 41
Figure 3: Parkinson’s Disease Market, Global, Efficacy Heat Map for Marketed Products (Part 2) 42
Figure 4: Pipeline for Parkinson’s Disease, Global, 2015 45
Figure 5: Pipeline for Parkinson’s Disease by Molecular Target, Global, 2015 46
Figure 6: Pipeline for Parkinson’s Disease by Mechanism of Action, Global, 2015 47
Figure 7: Parkinson’s Disease, Global, Average Clinical Trial Failure Rate (%), 2006–2015 49
Figure 8 : Parkinson’s Disease, Global, Clinical Trial Failure Rates for Small Molecules (%), 2006–2015 50
Figure 9: Parkinson’s Disease, Global, Clinical Trial Failure Rates by Mechanism of Action (%), 2006–2015 51
Figure 10: Parkinson’s Disease, Global, Clinical Trial Duration by Molecule Type, 2006–2015 52
Figure 11: Parkinson’s Disease, Global, Clinical Trial Duration by Mechanism of Action, 2006–2015 53
Figure 12: Parkinson’s Disease, Global, Clinical Trial Size by Molecule Type, 2006–2015 54
Figure 13: Parkinson’s Disease, Global, Clinical Trial Size by Mechanism of Action, 2006–2015 55
Figure 14: Pipeline for Parkinson’s Disease, Global, Comparison of Average Trial Metrics by Phase and Mechanism of Action, 2006–2015 56
Figure 15: Parkinson’s Disease Market, Global, Annual Sales of Opicapone ($m), 2015–2021 57
Figure 16: Parkinson’s Disease Market, Global, Annual Sales of Nuplazid ($m), 2016–2021 59
Figure 17 : Parkinson’s Disease Market, Global, Annual Sales of Nurelin ($m), 2016–2021 60
Figure 18: Parkinson’s Disease Market, Global, Annual Sales of Tozadenant ($m), 2018–2021 61
Figure 19: Parkinson’s Disease Market, Global, Annual Sales of APL-130277 ($m), 2017–2021 62
Figure 20: Parkinson’s Disease Market, Global, Annual Sales of P2B001 ($m), 2016–2021 63
Figure 21: Parkinson’s Disease Market, Global, Annual Sales of DM-1992 ($m), 2018–2021 64
Figure 22: Parkinson’s Disease Market, Global, Annual Sales of CVT-301 ($m), 2016–2021 65
Figure 23: Parkinson’s Disease Market, Global, Annual Sales of Dipraglurant IR ($m), 2019–2021 66
Figure 24: Parkinson’s Disease Market, Global, Annual Sales of the Accordion Pill ($m) 2018–2021 67
Figure 25: Parkinson’s Disease Market, Global, Annual Sales of ND-0612L ($m) 2019–2021 68
Figure 26: Parkinson’s Disease Market, Global, Efficacy Heat Map for Pipeline Products 70
Figure 27: Parkinson’s Disease Market, Global, Efficacy Heat Map for Pipeline Products 70
Figure 28: Parkinson’s Disease Market, Global, Efficacy Heat Map for Marketed Products 71
Figure 29: Parkinson’s Disease Market, Global, Efficacy Heat Map for Marketed Products 72
Figure 30: Parkinson’s Disease Market, Global, Product Competitiveness Early Parkinson’s Disease 73
Figure 31: Parkinson’s Disease Market, Global, Product Competitiveness Advanced Parkinson’s Disease 73
Figure 32: Parkinson’s Disease Market, Global, Treatment Patterns by Number of Patients (‘000), 2014–2021 75
Figure 33: Parkinson’s Disease Market, Global, Market Size ($m), 2014–2021 75
Figure 34: Parkinson’s Disease Market, US and Canada, Treatment Patterns by Number of Patients (‘000), 2014–2021 76
Figure 35: Parkinson’s Disease Market, US and Canada, Annual Cost of Therapy ($), 2014–2021 78
Figure 36: Parkinson’s Disease Market, US and Canada, Market Size ($), 2014–2021 79
Figure 37: Parkinson’s Disease Market, Top Five EU Countries, Treatment Patterns by Number of Patients (‘000), 2014–2021 80
Figure 38: Parkinson’s Disease Market, Tope Five EU Countries, Annual Cost of Therapy ($m), 2014–2021 82
Figure 39: Parkinson’s Disease Market, Top Five EU Countries, Market Size ($m), 2014–2021 83
Figure 40: Parkinson’s Disease Market, Japan, Treatment Patterns by Number of Patients (‘000) and the Annual Cost of Therapy ($), 2014–2021 84
Figure 41: Parkinson’s Disease Market, Japan, Market Size ($m), 2014–2021 85
Figure 42: Parkinson’s Disease Market, Global, Co-development Deals, 2006–2015 88
Figure 43: Parkinson’s Disease Market, Global, Co-development Deals by Molecule type and Stage of Development, 2006–2015 89
Figure 44: Parkinson’s Disease Market, Global, Co-development Deals by Mechanism of Action, 2006–2015 90
Figure 45: Parkinson’s Disease Market, Global, Licensing Deals, 2006–2015 92
Figure 46: Parkinson’s Disease Market, Global, Licensing Deals by Molecule Type and Stage of Development, 2006–2015 93
Figure 47: Parkinson’s Disease Market, Global, Licensing Deals by Molecular Targets and Aggregate Deal Value ($), 2006–2015 93
