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

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

Introduction

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.

Scope

*Analysis of the current unmet needs in cardiovascular disease markets

*Opinion leader commentary on key clinical trials and market landscape

*Review of the clinical and commercial status of stem cell therapy for cardiovascular disease

*Review of the clinical and commercial status of gene therapy for cardiovascular disease

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.

Reasons to Purchase

*Understand the need for innovation in the cardiovascular market.

*Up to date insight into the commercial and clinical status of cardiovascular gene and cell therapies

*Understand the barriers to commercialization of novel therapies, with expert commentary

ABOUT DATAMONITOR HEALTHCARE 2
About the Cardiovascular and Diabetes pharmaceutical analysis team: 2
CHAPTER 1 EXECUTIVE SUMMARY 3
Objective of the analysis 3
Datamonitor Key insights 3
Related reports 5
Acknowledgements 5
CHAPTER 2 BACKGROUND 8
Business Implications 8
Introduction 8
Scope 9
Definition of unmet needs 10
Clinical unmet needs in cardiovascular markets 10
Commercial Unmet Needs in cardiovascular markets 16
Commercial opportunities across cardiovascular indications 19
Response to the unmet need 22
Summary 23
CHAPTER 3 NOVEL DRUG TARGETS IN CV MEDICINE 24
Business Implications 24
Introduction 24
Bridging the "innovation gap" 25
Cardiovascular drug targets 25
New technologies allow expansion into novel targets 27
A lack of commercially viable drug targets 28
Biologics drive market growth 29
Monoclonal antibodies (MAbs) 30
Application of MAbs in cardiovascular disease 30
ReoPro (abciximab) profile 30
MAbs in the cardiovascular pipeline 31
BI-204 for atherosclerosis 31
TB-402 for thrombosis 33
Therapeutic vaccines 34
The need for therapeutic vaccines for chronic cardiovascular disease 34
Angiotensin vaccines for hypertension 34
Protherics's Angiotensin Therapeutic Vaccine 36
Cytos Biotechnology's CYT006-AngQ 36
Outlook for angiotensin vaccines 37
CHAPTER 4 STEM CELLS FOR USE IN CV MEDICINE 39
Business Implications 39
Introduction 39
The biology of stem cells 40
Derivation 41
Embryonic stem cells (ESCs) 42
Adult stem cells (ASCs) 42
The use of embryonic versus adult stem cells 43
Proliferation 43
Differentiation and pluripotency 44
Allogeneic versus autologous stem cells 44
The development timeline for stem cell technology 46
The exploitation of stem cells 47
Stem cell therapy 47
Use in regenerative medicine and tissue engineering 47
Stem cell transplantation 47
Stem cells for use in drug discovery 48
Screening arrays of compounds 48
Predictive toxicology 48
Stem cell therapy in cardiovascular medicine 48
Current status 48
The need for cardiovascular regeneration 49
Myocardial infarction and myocardial ischemia 49
Heart failure 50
Stem cell suitability for cardiovascular regeneration 50
Embryonic stem cells (ESCs) 51
Adult stem cells (ASCs) 51
Clinical development of stem cells for cardiovascular disease 54
Current clinical trial focus 54
Clinical trial results 57
Summary and future focus 66
Future clinical trial focus 67
Commercial landscape 69
International markets 70
Key players and products 70
Company Profiles 83
Aastrom Biosciences 83
Advanced Cell Technology 86
Angioblast Systems 88
Athersys 89
BioHeart 91
Cardio3BioSciences 93
Osiris Therapeutics 94
Development hurdles for stem cell therapy 96
Commercial risk associated with small companies 97
Research capacity 97
Regulation 100
Ethics and the perception of stem cells 101
Reimbursement 102
Intellectual property 102
CHAPTER 5 GENE THERAPY FOR USE IN CV MEDICINE 105
Business Implications 105
Introduction 106
Key definitions 106
Genomics 106
Gene therapy 107
The evolution of gene therapy 108
Discovery timeline 108
Approaches to gene therapy 110
In vivo versus ex vivo gene therapy 110
Gene delivery strategies 112
The use of vectors 112
Vector types 112
Delivery modalities 115
Systemic delivery 115
Non-systemic delivery 116
Disease targets for gene therapy 116
Research activity by indication 117
Cancer 117
Inherited diseases 118
Other targets 119
Gene therapy targets in cardiovascular disease 119
Therapeutic angiogenesis 124
Coronary artery disease (CAD) and myocardial ischemia 124
Peripheral arterial disease (PAD) 125
Heart failure 125
The beta-adrenergic (beta-AR) receptor signaling pathway 125
SERCA2a 126
Hypertension 127
ACE gene linked to high blood pressure in men 127
Targets in dyslipidemia 128
LDL-cholesterol and triglycerides 128
HDL-cholesterol 130
Other dyslipidemic targets 131
Gene therapies in the drug development pipeline 132
Current status 132
Current status of clinical trials of gene therapy 133
Gene therapy for coronary artery disease 133
Gene therapy for peripheral arterial disease 137
Gene therapy for heart failure 140
The beta-adrenergic receptor (beta-AR) signaling pathway 140
SERCA2a 140
Gene therapy for dyslipidemia 141
Gene therapy for hypertension 141
Future perspectives in gene therapy 142
Summary of preclinical and clinical research 142
Restenosis 142
Commercial landscape 143
International markets 143
Key players and products 144
Cardium Therapeutics 146
Development hurdles for gene therapy 148
Research and informatics 148
APPENDIX 150
Bibliography 150
About Datamonitor 154
About Datamonitor Healthcare 154
About the Cardiovascular Disease analysis team 155
Report methodology 155
Disclaimer 156
List of Tables
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
List of Figures
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