Stakeholder Opinions: Therapeutic Vaccines - A far-off promise of greatness

Introduction

The development of therapeutic vaccines has expanded beyond cancer indications and is attracting increasing interest from Pharma and Biotech, driven by potential advantages such as improved specificity, long-lasting immune response and cost-savings compared to conventional pharmacotherapy. First candidates have reached late-stage clinical development.

Scope

• Strategic analysis of therapeutic vaccine pipelines and key clinical candidates across several disease areas outside cancer
• Thorough assessment of opportunities and challenges for therapeutic vaccine development
• Review of potential strategies to increase the efficacy of therapeutic vaccines
• In-depth discussion of key target diseases, unmet needs and rationales for therapeutic vaccine development

Highlights

Efficacy and safety as well as the lack of suitable animal models remain key issues in therapeutic vaccine design and development. A prudent combination of suitable antigens, adjuvants and delivery systems will be crucial to creating efficacious therapeutic vaccines.

Other strategies to increase the efficacy of therapeutic vaccination may include a combination of therapeutic vaccination and pharmacotherapy as well as targeting of early-stage patients, who are more likely to mount a sufficient immune response.

Candidates for the treatment of substance dependence and diabetes have advanced furthest, whereas experts are more sceptical about the prospects of therapeutic vaccination in cardiovascular and autoimmune diseases. Disease-specific risk/benefit profiles will be key to regulatory approval.

Reasons to Purchase

• Review therapeutic vaccine progress in four key disease areas outside cancer
• Gain insight into the market environment for therapeutic vaccines through an analysis of pipelines, key candidates and regulatory trends
• Understand challenges, unmet needs and future opportunities by learning about the views of industry and academic key opinion leaders

TABLE OF CONTENTS

Overview 1

• Catalyst 1
• Summary 1

About Datamonitor healthcare 2

About the healthcare research & analysis team 2

Executive Summary 3

• Scope of the analysis 3
• Datamonitor insight into the therapeutic vaccines market 3
• Related reports 6
• Upcoming reports 7

Therapeutic vaccination – an overview 16

• Key findings 16
• General considerations 16
  
  • Therapeutic vaccines induce either T-cell or B-cell mediated immune responses 17
  • Dendritic cells (DCs) play a key initial role in human immunity. 17
  • T-cell based immune responses lead to an eradication of pathogens or infected cells by cytotoxic T-cells 18
  • B-cell based immune responses lead to the production of antibodies 19
• Monoclonal antibody therapy has laid a good foundation for therapeutic vaccine development in some disease areas 20
• Potential advantages and challenges of therapeutic vaccination 21

Advantages 22

• Therapeutic vaccines could offer targeted therapies with increased specificity 22
• The longevity of an immune response would reduce therapy times 22
• Therapeutic vaccination may be able to provide a cure for some diseases which currently require lifelong treatment 23
• Therapeutic vaccines could significantly reduce treatment costs for some indications 24

Challenges 24

• Lack of understanding of the disease mechanism handicaps therapeutic vaccine development in some indications 24
• Lack of involvement of Big Pharma is threatening progress in the sector 25
• Safety is a key concern for therapeutic vaccination approaches 26
• Reaching efficacy remains the main challenge for therapeutic vaccines 29
• Strategies used to increase the efficacy of therapeutic vaccines 30
  
  • Adjuvants can increase vaccine immunogenicity, but are often associated with safety concerns 30
  • Antigen design and delivery – advantages for organized antigen structures 32
  • Mucosal or dermal administration could offer benefits, but is perceived as less important by experts 33
  • Combination of therapeutic vaccines with standard therapy could increase efficacy 34
• Regulatory situation 35
• Overview of indications outside cancer targeted by therapeutic vaccines 37

Therapeutic vaccines in cardiovascular and metabolic diseases 42

• Key findings 42
• Overview 42
• Hypertension vaccines 43
  
  • Rationale for development of vaccines against hypertension 43
  • Disease background: over 25% of adults are suffering from hypertension 43
  • Compliance is a key challenge for existing hypertension therapy 43
  • Pipeline overview 44
  • Profiles of key candidates 46
  • CYT-006-AngQb (Cytos Biotechnology) 46
  • Angiotensin Therapeutic Vaccine (BTG) 48
  • Outlook for hypertension vaccines 49
• Atherosclerosis vaccines 50
  
  • Rationale for development of vaccines against atherosclerosis 50
  • Disease background: atherosclerosis is the main underlying condition for coronary heart disease or stroke 50
  • Current atherosclerosis treatment is based on statin therapy 51
  • Pipeline overview 52
  • Outlook for atherosclerosis vaccines 53
• Diabetes vaccines 54
  
  • Rationale for development of vaccines against diabetes 54
  • Disease background: the prevalence of diabetes is increasing due to an aging population and sedentary lifestyle 54
  • Vaccination could add significant value to diabetes therapy, particularly in type 1 patients 55
  • Pipeline overview 57
  • Profiles of key candidates 57
  • Diamyd (Diamyd Medical AB) 57
  • Outlook for diabetes vaccines 60

Therapeutic vaccines in CNS diseases 61

• Key findings 61
• Overview 61
• Substance dependence vaccines 62
  
  • Rationale for development of vaccines against substance dependence 62
  • Disease background: nicotine dependence is the most prevalent substance dependence 62
  • Current treatments are inadequate for preventing smoking relapse 63
  • Vaccination could provide a safe and more efficacious alternative to existing therapies 64
  • Pipeline overview 66
  • Profiles of key candidates 66
  • NicVAX (Nabi Biopharmaceuticals/GlaxoSmithKline) 66
  • NIC-002 (Novartis/Cytos Biotechnology) 69
  • TA-NIC (Celtic Pharma) 71
  • Niccine (Independent Pharmaceutica AB) 72
  • TA-CD (Celtic Pharma) 74
  • Outlook for substance dependence vaccines 75
• Alzheimer’s disease vaccines 77
  
  • Rationale for development of vaccines against Alzheimer’s disease 77
  • Disease background: Abeta and tau as main targets for future drugs 77
  • The number of people suffering from Alzheimer’s disease is increasing across the seven major markets 77
  • Current treatments are symptomatic, with no disease-modifying drugs available 78
  • Therapeutic vaccination appears a promising concept for the therapy of Alzheimer’s disease 78
  • The termination of AN1792 has taught valuable lessons for vaccine design 80
  • Pipeline overview 81
  • Profiles of key candidates 82
  • ACC-001 (Johnson & Johnson/Pfizer) 82
  • CAD-106 (Novartis/Cytos Biotechnology) 85
  • Outlook for Alzheimer’s disease vaccines 86

Therapeutic vaccines in autoimmune disorders 89

• Key findings 89
• Overview 89
• Rationale for development of vaccines against autoimmune diseases 90
  
  • Rheumatoid arthritis is a key target disease for vaccine makers 90
  • Disease background: rheumatoid arthritis is a chronic disease, mainly affecting the elderly 90
  • Antibody-based treatments have provided proof-of-concept for immunotherapy of rheumatoid arthritis 90
  • Vaccines could address several unmet needs in rheumatoid arthritis therapy 91
  • Multiple sclerosis is another key target for vaccine developers 92
  • Disease background: multiple sclerosis is a chronic disease causing severe damage to the central nervous system 92
  • Current treatment: interferons remain the backbone of multiple sclerosis therapy 93
  • Key unmet needs in multiple sclerosis therapy include improved efficacy and safety 93
  • Vaccination is a promising approach for the treatment of autoimmune diseases 94
• Pipeline overview 95
• Profiles of key candidates 96
  
  • Tovaxin (Opexa) 96
  • BHT-3009 (Bayhill Therapeutics) 99
• Outlook for therapeutic vaccines against autoimmune diseases 100

Therapeutic vaccines in infectious diseases 104

• Key findings 104
• Overview 104
• Hepatitis B therapeutic vaccines 105
  
  • Rationale for development of therapeutic vaccines against hepatitis B 105
  • Disease background: over 360 million people globally suffer from chronic hepatitis B 105
  • Current therapy is based on interferons and antivirals 106
  • Vaccination could improve efficacy, convenience and susceptibility to resistances 106
  • Pipeline overview 108
  • Profiles of key candidates 110
  • Hepatitis B virus vaccine (Emergent Biosolutions) 110
  • Outlook for therapeutic hepatitis B vaccines 112
• Hepatitis C therapeutic vaccines 113
  
  • Rationale for development of therapeutic vaccines against hepatitis B 113
  • Disease background – hepatitis C is a key underlying condition for cirrhosis and liver cancer 113
  • Current treatment gold standard is combination therapy with peginterferon / ribavirin 114
  • Unmet needs include efficacy in genotype 1 patients, tolerability and shorter treatment duration 115
  • Hepatitis C is a challenging target for vaccine developers 116
  • Pipeline overview 118
  • Profiles of key candidates 119
  • GI-5005 / HepCVax (GlobeImmune) 119
  • IC41 (Intercell) 121
  • ChronVac-C (Tripep/Inovio) 123
  • Outlook for therapeutic hepatitis C vaccines 125
• Human immunodeficiency virus (HIV) 126
  
  • Rationale for the development of therapeutic vaccines against HIV 126
  • Disease background – HIV prevalence is highest in the developing world 126
  • HAART has transformed HIV into a chronic disease, with many treatment options available 127
  • Viral eradication remains the most important unmet need in HIV therapy 128
  • Although promising in theory, vaccination against HIV faces significant challenges in practice 130
  • Pipeline overview 132
  • Clinical failure of Merck & Co’s prophylactic candidate has increased concerns regarding the feasibility of therapeutic HIV vaccination 134
  • Profiles of key candidates 135
  • Vacc-4x (Bionor Immuno) 135
  • AGS-004 (Argos Therapeutics/Kyowa Hakko Kirin) 136
  • Outlook for therapeutic HIV vaccines 137

Bibliography 140
Journals 140
Websites 148
Datamonitor reports 152
Appendix A 154

• Data definitions, limitations and assumptions 154
• Standard units 154
• Country group definitions 154
• Rest of European Union 154
• Middle East and North Africa (MENA) 154
• Rest of World 154

Appendix B 155

• Contributing experts 155
• Conferences attended 155
• Report methodology 155
• About Datamonitor 156
• About Datamonitor Healthcare 156
• About the Infectious Diseases analysis team 157
• Key therapy team members 158
• Holger Rovini, Head of Respiratory and Infectious Diseases 158
• Hedwig Kresse, Senior Analyst, Infectious Diseases 158
• Disclaimer 160