Stakeholder Opinions: Novel Therapeutic Approaches in Cardiovascular Medicine - Lack of market prospects for biologics expose an opportunity for cell and gene therapies

At the forefront of novel technologies; momentum is steadily building for the development of stem cell products to address cardiovascular disease. The most active areas are those with high clinical unmet need heart failure, cardiomyopathy and ishemic heart disease.

Report Highlights
Datamonitor's analysis demonstrates how the most innovative drugs offer the greatest growth potential for their respective markets. In the mature cardiovascular market, commercial success must be derived from innovative approaches with unique clinical benefits.

The array of innovative gene and cell products emerging from young companies exposes investment opportunities for venture capitalists, Big Pharma, as well as partnering opportunities for technology companies that can offer compatible catheters, or cell delivery devices.

There awaits an outstanding commercial opportunity for innovators who address clinical unmet need in this market, as a number of companies will see their key revenue generators melt away as they lose patent protection.
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ABOUT DATAMONITOR HEALTHCARE 2
About the Central Nervous System pharmaceutical analysis team 2
CHAPTER 1 EXECUTIVE SUMMARY 3
Scope of the analysis 3
Contributing experts 4
Datamonitor insight into the fibromyalgia market 5
Relevant reports 8
CHAPTER 2 MARKET OVERVIEW AND POTENTIAL 10
Definition and etiology 11
The cause and underlying mechanisms of fibromyalgia remain unknown 11
Research finds various chemical imbalances in patients 13
Proof of a genetic basis is hampered by patient heterogeneity 14
Diagnosis 14
American College of Rheumatology (1990) research criteria for fibromyalgia 15
1. History of widespread pain has been present for at least 3 months 15
2. Pain in 11 of 18 tender point sites on digital palpation 15
Co-morbidities 17
There are significant overlaps with other conditions 17
Epidemiology of fibromyalgia 18
Prevalence and incidence 19
Fibromyalgia is around seven times more common in women than men and increases with age 20
Experts and patient groups believe fibromyalgia is more common 21
Referral patterns, diagnosis and treatment rates 23
Patients are generally referred by primary care physicians to rheumatologists 23
Over half of the prevalent fibromyalgia population remain undiagnosed 24
Nearly all diagnosed patients receive drug therapy of some sort 25
Market sizing 25
Cheap generic drugs have historically made up the vast majority of fibromyalgia prescriptions 25
Clinical unmet needs 26
Need for a better understanding of disease etiology and pathophysiology 27
Need to improve pain reduction and control 28
Need to reduce sleep disturbances 29
CHAPTER 3 MARKETED BRAND DYNAMICS AND TREATMENT GUIDELINES 31
Marketed brands overview 32
Lyrica (pregabalin) 32
Drug overview 32
Forecast to 2017 38
Drug assessment 39
SWOT analysis 41
Pivotal clinical trial data 41
Other controlled clinical trials of Lyrica in fibromyalgia 45
Safety and tolerability 47
Treatment guidelines 49
European guidelines - EULAR evidence-based guidelines 49
Objectives - to provide evidence-based recommendations for the treatment of fibromyalgia 49
Methodology - developed by a multidisciplinary fibromyalgia task force representing 11 European countries 49
Results - 146 pharmacological and non-pharmacological studies were evaluated 51
EULAR recommendations 51
Meta-analysis was hampered by high variability in outcome measures used 53
US guidelines - the 2004 American Pain Society Guidelines 53
APS guidelines developed by an interdisciplinary panel of 13 pain management experts 53
APS guidelines recommend physicians start patients with a tricyclic antidepressant or cyclobenzaprine 54
New guidelines need to include new possible first-line options 54
CHAPTER 4 FORECAST ANALYSIS 56
Key events 57
Product launches in the US and 5EU 58
Product launches in Japan 58
Patent expiries 59
Data definitions, limitations and assumptions 61
Standard units 61
Derivation of sales forecasts and pricing trends 61
Forecast methodology 61
CHAPTER 5 PIPELINE OVERVIEW - R&D DYNAMICS AND APPROACH 62
Pipeline overview 63
Pipeline mainly consists of drugs indicated for other CNS indications 63
Classification of pipeline products 65
SNRI/NSRI antidepressants 65
GABA receptor modulators 66
Dopamine receptor agonists 67
Alpha adrenoceptor modulators 67
Others 68
Clinical trial design 68
Trials need to show improvements in both pain outcomes and function measures 68
Visual Analog Scale 69
Patient Experience Diary (PED) 69
Brief Pain Inventory 70
Patient Global Impression of Change (PGIC) scale 70
SF-36 physical component summary (PCS) score 70
Fibromyalgia Impact Questionnaire (FIQ) 71
OMERACT aims to standardize fibromyalgia endpoint requirements and measures 71
Agencies will review their clinical trial requirements based on OMERACT findings 71
OMERACT 8 continued work initiated at the first fibromyalgia workshop 2 years earlier 72
CHAPTER 6 LATE-STAGE DRUG ANALYSIS & FORECASTS 73
Late-stage pipeline comparative forecasts 74
Late-stage pipeline drug assessment summary 74
SNRI/NSRI antidepressant pipeline drugs 75
Cymbalta (duloxetine) 76
Drug overview 76
Forecasts to 2017 79
Drug assessment 80
Marketing factors 81
Patient potential 86
Clinical trial data 88
Milnacipran 97
Drug overview 97
Forecasts to 2017 99
Drug assessment 101
Marketing factors 101
Patient potential 104
Clinical trial data 105
Pristiq (desvenlafaxine) 114
Drug overview 114
Clinical trial data 115
AD-337 115
Drug overview 115
Clinical trial data 116
GABA receptor modulator pipeline drugs 117
Xyrem (sodium oxybate) 117
Drug overview 117
Forecasts to 2017 119
Drug assessment 120
Marketing factors 121
Patient potential 124
Clinical trial data 127
Lunesta (eszopiclone) 130
Drug overview 130
Clinical trial data 130
Dopamine receptor agonist pipeline drugs 131
Neupro (rotigotine) 133
Drug overview 133
Clinical trial data 134
Terguride 135
Drug overview 135
Clinical trial data 135
Alpha adrenoceptor modulator pipeline drugs 136
Esreboxetine 137
Drug overview 137
Clinical trial data 137
AGN 203818 139
Drug overview 139
Other pipeline drugs 139
Vimpat (lacosamide) 140
Drug overview 140
Clinical trial data 141
Neurotropin 142
Drug overview 142
Clinical trial data 142
NRC-027F 143
Drug overview 143
Flupirtine 143
Drug overview 143
Clinical trial data 144
PF-738502 145
Drug overview 145
CHAPTER 7 COMMERCIAL IMPACT AND CASE STUDY ANALYSIS 146
Introduction 147
Evaluation of Pfizer's successful Lyrica launch strategy 147
Pfizer sponsored unbranded fibromyalgia advertising campaign 148
Pfizer launches branded DTC campaign 150
BIBLIOGRAPHY 155
Journal papers, books, and conference abstracts 155
Websites 164
Datamonitor reports 171
APPENDIX 173
Market sizing calculations 173
Methodology, assumptions and caveats 176
Top 10 prescribed products for fibromyalgia (minus Lyrica and Cymbalta) in the 5EU and Japan in 2007 178
Clinical guidelines - classification schemes 179
Recently discontinued fibromyalgia projects or those assumed on-hold 180
5EU IMS standard unit dose-dependent Lyrica prices 181
Report methodology 181
Contributing experts 183
About Datamonitor 183
About Datamonitor Healthcare 184
About the Disease analysis team 184
Disclaimer 186
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Table 1: Summary of clinical unmet needs across the main cardiovascular indications, 2008 12
Table 2: Family classification of drug targets 26
Table 3: ReoPro: Overview 31
Table 4: Key clinical trials using stem cells in acute myocardial infarction, 2008 58
Table 5: Key clinical trials using stem cells in heart failure, 2008 63
Table 6: Key unknowns in cardiovascular stem cell therapy 69
Table 7: Stem cell products currently in development for cardiovascular indications, 2008 72
Table 8: Stem cell companies developing products for cardiovascular indications (Listed) 77
Table 9: Stem cell companies developing products for cardiovascular indications (Non-listed) 81
Table 10: Comparison of different gene vectors used for gene transfer 113
Table 11: Potential delivery methods for different vectors in cardiovascular disease 116
Table 12: Genetic targets in cardiovascular disease 121
Table 13: Effects of overexpressing SR Ca2+ pump in myocytes isolated from failing human hearts 127
Table 14: Key clinical trials in gene therapy for CAD 134
Table 15: Key clinical trials in gene therapy for PAD 138
Figure 1: Chapter 2 - Business Implications 8
Figure 2: The $ sales plateau in the cardiovascular market, 2006-2016 17
Figure 3: US patent expiries of the top 10 cardiovascular brands, 2006-2016 18
Figure 4: Summary of unmet needs in cardiovascular indications, 2008 23
Figure 5: Chapter 3 - Business Implications 24
Figure 6: Technological advances expand the conceptual 'druggable' space 27
Figure 7: Key characteristics influencing pharmaceutical commercial attractiveness 29
Figure 8: The mechanism through which the renin-angiotensin-aldosterone system induces systemic hypertension 35
Figure 9: Chapter 4 - Business Implications 39
Figure 10: Definition of terms in the stem cell differentiation process 41
Figure 11: US and UK milestones in the development of stem cell technology, 1950-2008 46
Figure 12: Summary of current focus of stem cell technology in cardiovascular disease, 2008 49
Figure 13: Expert comment: maximizing useful progenitor cells per sample volume is an important consideration 54
Figure 14: Development hurdles for embryonic stem cells 56
Figure 15: Expert comment: future clinical trial focus for stem cell therapy in cardiovascular disease 68
Figure 16: Cardiovascular stem cell therapies in clinical development, 2008 71
Figure 17: Proposed research, development and marketing protocol for stem cell therapies 99
Figure 18: Chapter 5 - Business Implications 105
Figure 19: Timeline of key developments in gene therapy 109
Figure 20: In vivo versus ex vivo gene transfer 111
Figure 21: Reserch activity in gene therapy, according to number of clinical trials, by indication 119
Figure 22: Summary of current focus of gene therapy research in cardiovascular disease, 2008 132
Figure 23: Reserch activity in gene therapy, according to number of clinical trials, by location 144
Figure 24: Cardiovascular stem cell therapies in clinical development, 2008 145
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