OpportunityAnalyzer: Dengue Vaccines – Opportunity Analysis and Forecasts to 2020 – Event-Driven Update

Summary

Dengue is a febrile illness caused by the dengue virus (DENV), a single-stranded flavivirus most commonly transmitted by the Aedes aegypti (A. aegypti) mosquito. Thought to be responsible for upwards of 100 million infections each year, DENV is the most prevalent arthropod-borne virus in the world. Individuals infected with DENV can present with a wide spectrum of symptoms, including fevers, retro-orbital pain, severe headache, muscle and joint pain, and rash. The severity of dengue fever ranges from asymptomatic cases, to classic dengue fever, and to dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) that have a mortality rate of 5%-15%. Because there are no marketed dengue-specific vaccines or therapeutics, current treatment strategies are limited to supportive care for those already infected with the virus, and vector control to reduce DENV transmission. The near-universal failure of these measures to curtain transmission and reduce disease burden across the global marketplace – which for the purposes of this report is comprised of Brazil, India, Mexico, Singapore, and Thailand – has further enhanced the need for safe and effective vaccines. GlobalData expects the launch of the first dengue vaccines, led by Sanofi Pasteur’s CYD-TDV and Takeda’s TAK-003, to revolutionize the treatment and prevention paradigm.

Highlights

Key Questions Answered

– Based on interviews with key opinion leaders (KOLs), GlobalData has identified the major unmet needs in the dengue vaccine marketplace. Will the leading pipeline agents fulfil these unmet needs during the forecast period (2015-2020)?
– What research and development (R&D) strategies will companies leverage to compete in the future dengue vaccine marketplace?
– Which patient population(s) are most likely to be targeted for routine and catch-up immunization?
– What clinical and environmental factors are likely to influence dengue vaccine uptake in Brazil, India, Mexico, Singapore, and Thailand? Which of these markets will experience the strongest growth from 2015-2020?

Key Findings

– GlobalData projects the dengue vaccine market in Brazil, India, Mexico, Singapore, and Thailand to grow from $50.8m in 2015 to $486.2m in 2020, at a compound annual growth rate (CAGR) of 57.1%. This rapid growth will be driven by the expected incorporation of newly-launched dengue vaccines into routine and catch-up immunization programs.
– KOLs interviewed by GlobalData expect the live-attenuated dengue vaccines – led by Sanofi Pasteur’s CYD-TDV and Takeda’s TAK-003 – to dominate the marketplace for the duration of the forecast period.
– GlobalData anticipates that firms will increasingly turn to innovative R&D strategies, in particular the exploration of alternative approaches to early-stage clinical trial design – such as the dengue human infection model (DHIM) – in order to increase developmental efficiency, minimize upfront risk, and gain a competitive advantage over rivals.
– Domestically-supplied vaccines, most notably Butantan Institute’s TV-003 in Brazil and Panacea Biotech’s/Biological E’s TV-003 in India, are projected to limit market growth due to their low price relative to vaccines produced by privately-held foreign companies.

Scope

– Overview of dengue virus (DENV), including epidemiology, etiology, pathophysiology, symptoms, diagnosis, and current disease surveillance and prevention measures.
– Topline dengue vaccine market revenue from 2015-2020. Annual cost of therapy (ACOT) and major pipeline vaccine sales in this forecast period are included.
– Key topics covered include strategic competitor assessment, market characterization, unmet needs, R&D strategies, and clinical trial design for the dengue vaccine market.
– Pipeline analysis: comprehensive data split across different phases, emerging novel trends under development, synopses of innovative early-stage projects, and detailed analysis of late-stage pipeline vaccines. An interactive clinical and commercial analyzer tool is available.
– Analysis of the current and future market competition in the global dengue vaccine market. Insightful review of the key industry drivers, restraints and challenges. Each trend is independently researched to provide qualitative analysis of its implications.

Reasons to buy

– Develop and design your in-licensing and out-licensing strategies through a review of pipeline products and technologies, and by identifying the companies with the most robust pipeline.
– Develop business strategies by understanding the trends shaping and driving the global dengue vaccine market.
– Drive revenues by understanding the key trends, innovative products and technologies, market segments, and companies likely to impact the dengue vaccine market in the future.
– Formulate effective sales and marketing strategies by understanding the competitive landscape and by analysing the performance of various competitors.
– Identify emerging players with potentially strong product portfolios and create effective counter-strategies to gain a competitive advantage.
– Organize your sales and marketing efforts by identifying the market categories and segments that present maximum opportunities for consolidations, investments and strategic partnerships.

1 Table of Contents
1 Table of Contents 11
1.1 List of Tables 16
1.2 List of Figures 18
2 Introduction 19
2.1 Catalyst 19
2.2 Related Reports 20
2.3 Upcoming Related Reports 21
3 Disease Overview 22
3.1 Etiology and Pathophysiology 22
3.1.1 Etiology 22
3.1.2 Pathophysiology 25
3.2 Symptoms 28
3.3 Prognosis 31
4 Epidemiology 32
4.1 Disease Background 32
4.2 Risk Factors and Comorbidities 32
4.3 Global Trends 35
4.3.1 Incidence and Geographic Distribution 35
4.3.2 Dengue Periodic and Seasonal Patterns 37
4.3.3 Dengue Serotypes 38
4.4 Forecast Methodology 39
4.4.1 Sources Used 41
4.4.2 Sources Not Used 44
4.4.3 Forecast Assumptions and Methods 44
4.5 Epidemiological Forecast for Dengue (2013-2023) 47
4.5.1 Reported Laboratory-Confirmed Dengue Cases 47
4.5.2 Sex-Specific Distribution of Reported Laboratory-Confirmed Dengue Cases 49
4.5.3 Age-Specific Distribution of Reported Laboratory-Confirmed Dengue Cases 51
4.5.4 Age-Standardized Incidence of Reported Laboratory-Confirmed Dengue 53
4.6 Discussion 55
4.6.1 Epidemiological Forecast Insight 55
4.6.2 Limitations of the Analysis 56
4.6.3 Strengths of the Analysis 57
5 Current Surveillance, Prevention, and Control Measures 58
5.1 Overview 58
5.2 Brazil 64
5.2.1 Surveillance and Diagnosis 64
5.2.2 Vector Control 65
5.2.3 Immunization Recommendations and Infrastructure 66
5.3 India 68
5.3.1 Surveillance and Diagnosis 69
5.3.2 Vector Control 69
5.3.3 Immunization Recommendations and Infrastructure 70
5.4 Mexico 72
5.4.1 Surveillance and Diagnosis 73
5.4.2 Vector Control 74
5.4.3 Immunization Recommendations and Infrastructure 75
5.5 Singapore 78
5.5.1 Surveillance and Diagnosis 78
5.5.2 Vector Control 79
5.5.3 Immunization Recommendations and Infrastructure 79
5.6 Thailand 81
5.6.1 Surveillance and Diagnosis 81
5.6.2 Vector Control 82
5.6.3 Immunization Recommendations and Infrastructure 82
6 Unmet Needs Assessment and Opportunity Analysis 85
6.1 Overview 85
6.2 Unmet Needs Analysis 87
6.2.1 Unmet Need: Safe and Efficacious Vaccines 87
6.2.2 Unmet Need: An Improved Understanding of Dengue Immunity 89
6.2.3 Unmet Need: Reliable Immunological Correlates of Protection 90
6.2.4 Unmet Need: Country-Specific Immunization Program Preparedness 90
6.2.5 Unmet Need: Upgraded Vector Control and Surveillance Infrastructures 91
6.2.6 Unmet Need: Improved Diagnostic Tools 92
6.2.7 Unmet Need: High-Quality Animal Models 93
6.3 Opportunity Analysis 94
6.3.1 Opportunity: Develop a Single-Dose Dengue Vaccine 94
6.3.2 Opportunity: Further Elucidate the Role(s) of T Cells in Dengue Immunity 95
6.3.3 Opportunity: Streamline Vaccine Development with Innovative Clinical Trial Design 96
6.3.4 Opportunity: Partner with Public Health Stakeholders to Integrate Vaccines into Multifaceted Dengue Prevention Programs 96
6.3.5 Opportunity: Establish Country-Specific Vaccine Launch Strategies 97
6.3.6 Opportunity: Leverage Diagnostics to Demonstrate Vaccine Effectiveness Post-Licensure 98
7 Research and Development Strategies 100
7.1 Overview 100
7.2 Technological Approaches to Vaccine Development 100
7.2.1 Vaccine Antigen Selection 100
7.2.2 Tetravalent Vaccine Construction 102
7.3 Partnerships, Acquisitions, and Licensing Agreements 104
7.4 Clinical Trial Design 106
7.4.1 Current Clinical Trial Design 106
7.4.2 Inclusion of Representative Patient Populations in Clinical Trials 110
7.4.3 Demonstration of Protective Efficacy 111
7.4.4 Dengue Human Infection Model 112
8 Pipeline Assessment 114
8.1 Overview 114
8.2 Live-Attenuated Vaccines in Clinical Development 120
8.2.1 CYD-TDV 120
8.2.2 TAK-003 133
8.2.3 TV-003 139
8.3 Other Vaccines in Clinical Development 145
8.3.1 TDENV-PIV 145
8.3.2 DEN-80E 148
8.4 Vaccines in Preclinical Development 151
9 Pipeline Valuation Analysis 153
9.1 Clinical Benchmarking of Key Pipeline Vaccines 153
9.2 Commercial Benchmarking of Key Pipeline Vaccines 155
9.3 Competitive Assessment 157
9.4 Top-Line Five-Year Forecast 159
9.4.1 Brazil 163
9.4.2 India 165
9.4.3 Mexico 167
9.4.4 Singapore 168
9.4.5 Thailand 169
10 Appendix 172
10.1 Bibliography 172
10.2 Abbreviations 193
10.3 Methodology 197
10.4 Forecasting Methodology 197
10.4.1 Vaccinated Patients 197
10.4.2 Vaccination Coverage Rates 198
10.4.3 Vaccines Included in Each Class 198
10.4.4 Vaccine Launch Dates 198
10.4.5 General Pricing Assumptions 199
10.4.6 Individual Vaccine Assumptions 200
10.4.7 Pricing of Pipeline Vaccines 203
10.5 Physicians and Specialists Included in this Study 206
10.6 About the Authors 208
10.6.1 Analyst 208
10.6.2 Epidemiologist 208
10.6.3 Therapy Area Director 209
10.6.4 Global Head of Healthcare 209
10.7 About GlobalData 210
10.8 Disclaimer 210

1.1 List of Tables
Table 1: Symptoms and WHO Case Definitions of Dengue 29
Table 2: Risk Factors for DENV Transmission and Severe Dengue (DHF and DSS) 34
Table 3: Periodicity and Seasonality of Dengue Fever in the 5MM, 2003-2013 38
Table 4: 5MM, Circulating DENV Serotypes and Predominant Serotype, 2003-2013 39
Table 5: 5MM, Sources of Reported Laboratory-Confirmed Dengue Fever Data 40
Table 6: 5MM, Reported Laboratory-Confirmed Dengue Cases, N (Col %), Men and Women, All Ages, Selected Years, 2009-2023 48
Table 7: 5MM, Sex-Specific Distribution of Reported Laboratory-Confirmed Dengue Cases, All Ages, Annual Average, 2009-2013 50
Table 8: 5MM, Age-Specific Distribution of Reported Laboratory-Confirmed Dengue Cases, All Ages, Annual Average, 2009-2013 52
Table 9: Routine Immunization Recommendations in Brazil, 2014 67
Table 10: Routine Immunization Recommendations in India, 2014 71
Table 11: Routine Immunization Recommendations in Mexico, 2014 76
Table 12: Routine Immunization Recommendations in Singapore, 2014 80
Table 13: Routine Immunization Recommendations in Thailand, 2014 83
Table 14: Unmet Need and Opportunity in Dengue Vaccines 87
Table 15: Acquisitions and Licensing Agreements in the Dengue Vaccine Market, 2014 105
Table 16: Design of Selected Dengue Vaccine Clinical Trials 108
Table 17: Dengue Vaccines - Clinical Development Pipeline, 2014 115
Table 18: Comparison of Dengue Vaccine Classes in Clinical Development, 2014 119
Table 19: Product Profile - CYD-TDV 123
Table 20: Phase III Efficacy Profile - CYD-TDV 126
Table 21: Exploratory Intent-to-Treat Efficacy Analyses — CYD-TDV 128
Table 22: Phase IIb Efficacy Profile - CYD-TDV 130
Table 23: Safety Profile - CYD-TDV 131
Table 24: CYD-TDV SWOT Analysis, 2014 132
Table 25: Product Profile - TAK-003 135
Table 26: Efficacy Profile - TAK-003 136
Table 27: Safety Profile - TAK-003 137
Table 28: TAK-003 SWOT Analysis, 2014 138
Table 29: Product Profile - TV-003 141
Table 30: Efficacy Profile - TV-003 142
Table 31: Safety Profile - TV-003 143
Table 32: TV-003 SWOT Analysis, 2014 144
Table 33: Product Profile - TDENV-PIV 146
Table 34: TDENV-PIV SWOT Analysis, 2014 147
Table 35: Product Profile - DEN-80E 149
Table 36: Efficacy Profile - DEN-80E 150
Table 37: DEN-80E SWOT Analysis, 2014 151
Table 38: Dengue Vaccines - Innovative Vaccines in Preclinical Development, 2014 152
Table 39: Clinical Benchmarking of Key Pipeline Vaccines 154
Table 40: Commercial Benchmarking of Key Pipeline Vaccines 156
Table 41: Top-Line Sales Forecast ($m) for Dengue Vaccines, 2015-2020 160
Table 42: Key Events Impacting Sales for Dengue Vaccines, 2015-2020 162
Table 43: Dengue Vaccines Market - Drivers and Barriers, 2015-2020 163
Table 44: Key Launch Dates 199

1.2 List of Figures
Figure 1: DENV Structure and Genome 24
Figure 2: Laboratory Methods for Dengue Diagnosis 27
Figure 3: 5MM, Incidence Rate (Cases per 100,000 Population) of Reported Laboratory-Confirmed Dengue Cases (Including Classic Dengue Fever and DHF), Men and Women, All Ages, 2003-2013 36
Figure 4: 5MM, Reported Laboratory-Confirmed Dengue Cases, Men and Women, All Ages, 2014-2023 49
Figure 5: 5MM, Sex-Specific Distribution of Reported Laboratory-Confirmed Dengue Cases, All Ages, Annual Average, 2009-2013 51
Figure 6: 5MM, Age-Specific Distribution of Reported Laboratory-Confirmed Dengue Cases, Men and Women, Annual Average, 2009-2013 53
Figure 7: 5MM, Age-Standardized Incidence of Reported Laboratory-Confirmed Dengue Cases, All Ages, Annual Average, 2009-2013 54
Figure 8: Competitive Assessment of Pipeline Dengue Vaccines, 2015-2020 158
Figure 9: Global Dengue Vaccine Uptake, by Routine or Catch-up Immunization, 2015-2020 160
Figure 10: Global Sales for Pipeline Dengue Vaccines by Country, 2015-2020 161
Figure 11: Brazil Dengue Vaccine Uptake, by Routine or Catch-up Immunization, 2015-2020 164
Figure 12: India Dengue Vaccine Uptake, by Routine or Catch-up Immunization, 2015-2020 166
Figure 13: Mexico Dengue Vaccine Uptake, by Routine or Catch-up Immunization, 2015-2020 167
Figure 14: Singapore Dengue Vaccine Uptake, by Routine or Catch-up Immunization, 2015-2020 169
Figure 15: Thailand Dengue Vaccine Uptake, by Routine or Catch-up Immunization, 2015-2020 170