OPPORTUNITY ANALYSIS AND FORECASTS TO …TV-003 in India — will stymie market growth due to their...

REFERENCE CODE GDHC022POA | PUBLICAT ION DATE JULY 2014

DENGUE VACCINES - OPPORTUNITY ANALYSIS AND FORECASTS TO 2020

Dengue Vaccines - Opportunity Analysis and Forecasts to 2020 2 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form.


Executive Summary

Dengue Vaccines: Key Metrics in Brazil, India, Mexico, Singapore, and Thailand, 2015–2020 2015 Vaccination Coverage

Targeted Population(s) 1,651.3 million

Vaccinated Population(s) 0.5 million

2015 Market Sales

Brazil $44.6m

India N/A

Mexico $23.6m

Singapore $1.4m

Thailand N/A

Total $69.6m

Pipeline Assessment

Number of vaccines in Phase I–III 5

Number of first-in-class vaccines 4

Key Events (2015–2020) Level of Impact

Launch of Sanofi’s CYD-TDV in Brazil, Mexico, Singapore, and Thailand

Launch of Sanofi’s CYD-TDV in India

Launch of Takeda’s DENVax in Brazil, Mexico, Singapore, and Thailand

Launch of the Butantan Institute’s domestically-produced TV-003 in Brazil

Launch of Panacea Biotech’s/Biological E’s domestically-produced TV-003 in India

2020 Vaccination Coverage

Targeted Population(s) 1,741.6 million

Vaccinated Population(s) 20.0 million

2020 Market Sales

Brazil $97.0m

India $58.6m

Mexico $216.7m

Singapore $16.1m

Thailand $10.0m

Total $398.6m

Source: GlobalData, based on primary research interviews with dengue vaccine specialists N/A: Not applicable

The table above presents the key metrics for

dengue vaccines in the five pharmaceutical

markets covered in this report (Brazil, India,

Mexico, Singapore, and Thailand) during the

forecast period from 2015–2020.

After the Launch of the First Dengue Vaccine in 2015, the Market is Projected to Experience Rapid Growth Through 2020

In 2015, GlobalData projects the dengue vaccine

market to be valued at $69.6m across the five

pharmaceutical markets covered in this report:

Brazil, India, Mexico, Singapore, and Thailand.

Two of the earliest adopters of dengue vaccines,

Brazil and Mexico, are together expected to

account for well over 95% of the 2015 market

share, with sales of $44.6m (64.1% market share)

and $23.6m (34.0% market share), respectively.

For the purposes of this report, GlobalData defines

the market as the sales of dengue vaccines in the

countries of interest that are likely to incorporate

these vaccines into their routine immunization

programs.

By 2020, GlobalData expects dengue vaccine

sales to grow substantially and reach a combined

$398.6m in Brazil, India, Mexico, Singapore, and

Thailand, at a Compound Annual Growth Rate

(CAGR) of 41.8%. This rapid uptake of dengue

vaccines will be driven primarily by the inclusion of

live-attenuated vaccines in national immunization

programs. Brazil ($97.0m; 24.4% market share)

and Mexico ($216.7m; 54.4% market share) are

anticipated to continue their dominance of the



Executive Summary

market, although GlobalData projects India

($58.6m; 14.7% market share), Singapore

($16.1m; 4.0% market share), and Thailand

($10.0m; 2.5% market share) to still experience

solid growth from 2015–2020. Sales growth,

however, will likely be hindered by the arrival of

less expensive, publically-supplied vaccines in

Brazil and India, which are expected to rapidly

garner patient share from premium-priced

vaccines.

Given their superior clinical and commercial

positioning, GlobalData anticipates that live-

attenuated dengue vaccines — led by Sanofi’s

CYD-TDV and Takeda’s DENVax — will dominate

the market, with 2020 sales projected to reach

$166.4m (41.8% market share) and $148.5m

(37.3% market share) across the five

pharmaceutical markets covered in this report,

respectively. Despite being second to market,

GlobalData expects DENVax to seize significant

market share from Sanofi’s first-to-launch vaccine

due to its more convenient dosing schedule and a

competitive pricing strategy. Despite their overall

market dominance, GlobalData projects both CYD-

TDV and DENVax to lose market share to the

domestically-produced live-attenuated vaccine, TV-

003 ($80.2m; 20.1% market share), in Brazil and

India by 2020, primarily because of its lower price.

GlobalData expects the earlier-stage pipeline

vaccines — GlaxoSmithKline’s (GSK’s) TDENV-

PIV and Merck’s DEN-80E — to garner less than

1% market share by 2020.

GlobalData expects the major drivers of growth in

the dengue vaccine market across Brazil, India,

Mexico, Singapore, and Thailand to include:

The launch of the first live-attenuated dengue

vaccines, particularly Sanofi’s CYD-TDV and

Takeda’s DENVax. These vaccines will be

heralded by physicians, public health officials,

and policymakers as a welcome relief to the

growing global healthcare burden of dengue.

Dengue’s growing socioeconomic and public

health burden will lead countries to push for

widespread immunization as a preventative

measure. Specifically, the past failures of

vector control initiatives to curtail the spread of

the Aedes aegypti mosquito have left a glaring

void in the prevention and landscape, which

will hasten the uptake of vaccines.

The integration of dengue vaccines into routine

childhood immunization schedules. Taking into

account the existing immunization program

infrastructure and disease epidemiology,

GlobalData’s primary research indicates that

targeting the pediatric population for

vaccination will likely improve coverage rates

and provide a sustained revenue source for

vaccine manufacturers.



Executive Summary

GlobalData anticipates the formidable barriers to

growth in the dengue vaccine market across Brazil,

India, Mexico, Singapore, and Thailand to include:

Formidable logistical and financial hurdles

must be overcome in order to successfully

assimilate a novel vaccine into the

immunization program infrastructure of

developing nations. GlobalData projects the

growth in these markets to be slowed by these

barriers relative to novel vaccine adoption in

the developed markets.

Domestically-supplied vaccines — most

notably, the Butantan Institute’s TV-003 in

Brazil and Panacea Biotech’s/Biological E’s

TV-003 in India — will stymie market growth

due to their low cost relative to vaccines

produced by privately-held foreign companies.

The failure of current disease surveillance

programs and vector control programs in

developing nations may slow growth in the

dengue vaccines marketplace, as key opinion

leaders (KOLs) view the integration of vaccines

into a holistic prevention program as the most

promising approach to dengue control.

The figure below illustrates the expected sales for

dengue vaccines in Brazil, India, Mexico,

Singapore, and Thailand at the beginning and

conclusion of the forecast period

Sales for Dengue Vaccines by Country, 2015–2020

64.1%

34.0%

2.0%

Brazil

India

Mexico

Singapore

Thailand

2015Total: $69.6m

24.3%

14.7%

54.4%

4.1% 2.5%

2020Total: $398.6m

Source: GlobalData, based on primary research interviews with dengue vaccine specialists



Executive Summary

From a Barren to Competitive Market: Vaccine Developers Will Need to Leverage Innovative R&D Strategies to Differentiate Themselves from Their Rivals

Over the last several years, much progress has

been made towards the development of safe and

effective dengue vaccines. As of May 2014, six

investigational vaccines were being studied in

humans, and the leader of these pipeline

candidates, Sanofi Pasteur’s CYD-TDV, is

currently undergoing Phase III efficacy and safety

studies. The desire to bring the first dengue

vaccines to market has led companies to utilize a

variety of different research and development

(R&D) strategies, which include diverse

approaches to antigen construction, vaccine

formulation, and clinical trial design. Since 2008,

Big Pharma has demonstrated its desire to

penetrate this untapped market, increasing its

stake in the marketplace through partnerships,

licensing deals, and acquisitions. However, as the

dengue vaccine marketplace becomes increasingly

crowded over the forecast period (2015–2020),

GlobalData anticipates that firms will 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 their rivals.

High Unmet Need for Safe and Efficacious Dengue Vaccines Expected to Facilitate Rapid Uptake of Pipeline Agents

GlobalData classifies the overall level of unmet

need in the global dengue vaccines marketplace

as high. As the morbidity and mortality associated

with dengue continue to climb, KOLs agree that the

absence of a safe and efficacious dengue vaccine

represents the greatest unmet need across the five

markets covered in this report: Brazil, India,

Mexico, Singapore, and Thailand. The failure of

vector control to limit the spread of the virus’

mosquito vectors has further boosted the

importance of vaccines as an additional disease

prevention tool. GlobalData expects that the high

level of unmet need in the marketplace will lead to

the rapid incorporation of live-attenuated dengue

vaccines into routine childhood immunization

programs, with Brazil, Mexico, Singapore, and

Thailand quickly achieving ≥90% coverage rates

within the projected target age cohort of two years

by 2017. Slowed by poor disease surveillance and

a weak immunization program infrastructure

relative to the other four markets, GlobalData

projects India to more gradually incorporate novel

dengue vaccines into its childhood vaccination

schedule, with coverage rates only topping 60% by

2020.



Executive Summary

Opportunities for Current and Future Players to Exploit Gaps in the Treatment Landscape Will Exist Throughout the Forecast Period and Beyond

While GlobalData expects several dengue

vaccines with solid clinical profiles, led by Sanofi

Pasteur’s CYD-TDV and Takeda’s DENVax, to

receive licensure during the forecast period,

opportunities will still exist for later entrants to

compete with these first-in-class products. Experts

revealed to GlobalData that vaccine developers

should focus their efforts on evaluating more

convenient vaccine dosing schedules, gaining an

improved understanding of dengue immunity,

identifying more robust immunological correlates of

protection, exploring novel approaches to clinical

trial design, and improving animal models in order

to best position their respective pipeline products.

From a commercial perspective, GlobalData

contends that companies must prioritize engaging

healthcare policymakers and other stakeholders in

order to expedite the launch of new dengue

vaccines. Historically, vaccine launches in the

developing world have taken several years, so

early planning is essential for the rapid adoption of

new dengue vaccines. Dengue vaccine developers

must adopt a country-specific approach to planning

for vaccine adoption, as this strategy represents an

attractive opportunity for positioning a vaccine for

rapid adoption in multiple countries once it receives

regulatory approval. KOLs also indicated that one

of the most important issues that must be

addressed pre-launch is vaccine pricing, a factor

that will heavily influence the rate and extent of

uptake in low- and middle-income nations.

Developers will also need to consider that

healthcare policymakers will take into account how

vector control and disease surveillance spending

will influence a country’s ability to afford mass

dengue immunization programs.

Live-Attenuated Vaccines, Led by Sanofi’s CYD-TDV, are Expected to Dominate the Dengue Vaccine Marketplace from 2015–2020

While the dengue vaccine pipeline possesses a

high level of diversity in terms of vaccine class and

technological approach, GlobalData expects the

live-attenuated vaccines, which include Sanofi

Pasteur’s CTD-TDV, Takeda’s DENVax, and the

US National Institute of Health’s (NIH’s) TV-003

(licensed to the Butantan Institute in Brazil and

Panacea Biotech/Biological E in India), to rule the

marketplace for the duration of the forecast period.

Despite lingering questions regarding their safety

and ability to provide balanced short- and long-

term protection against the four dengue virus

(DENV) serotypes, KOLs interviewed by

GlobalData cited live-attenuation as the most

promising technological approach to dengue

vaccine R&D. While the other vaccine classes in

clinical development — inactivated virus, subunit,

and deoxyribonucleic acid (DNA) vaccines — may

theoretically minimize the chance of viral

interference and could be perceived as safer by

patients, KOLs overwhelmingly viewed them as



Executive Summary

inferior to live-attenuated vaccines and cited their

need for adjuvants and late arrival to the

marketplace as key weaknesses. GlobalData

projects live-attenuated dengue vaccines to

account for over $395m in sales by 2020, with a

CAGR of 41.5% from 2015–2020.

The figure below summarizes competitive

assessment of the most promising dengue vaccine

candidates in clinical development from 2015–

2020. GlobalData based the ratings for each

pipeline agent’s clinical and commercial attributes

on discussions with KOLs from across the markets

covered in this report, analysis of clinical trial data,

and a thorough review of the literature.

Competitive Assessment of Pipeline Dengue Vaccines, 2015–2020

CYD-TDV

DENVax

TV-003TDENV-PIV

DEN-80E

D1ME-VR-P*

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0

Com

mer

cial

Sco

re

Clinical Score Source: GlobalData, based on primary research interviews with dengue vaccine specialists *D1ME-VR-P is not projected to launch during the forecast period.

What Do Physicians and Specialists Think?

KOLs interviewed for this report shared their expert

insight on the dengue vaccine market. These

experts cite factors such as the failure of disease

surveillance programs and vector control

measures, the popularization of air travel,

globalization, and urbanization as all having

contributed in some way to the increased incidence

of dengue throughout the world, especially in Asia

and Latin America.

“The large epidemics of dengue and the virus’

geographical expansion are closely tied to the

dramatic urban growth that has occurred in tropical

developing countries over the past 40 years. With

the advent of the jet airplane, globalization, and the

movement of people, animals, and commodities, I

see no reason that these trends are going to

change because of any disease. What we have to

do is figure out how to control this disease, despite

these global changes or global trends.”

Asia-Pacific Key Opinion Leader

“Dengue is a disease that for the last forty

years…has been growing in a very systematic

way, mostly linked to the process of urbanization.”

Americas Key Opinion Leader

“Out of Brazil, Mexico, India, Singapore, and

Thailand, none of these countries have done a

very good job of controlling the spread of dengue.”




Executive Summary

KOLs also agreed that the absence of a safe and

efficacious dengue vaccine represents the greatest

unmet need across the five markets covered in this

report: Brazil, India, Mexico, Singapore, and

Thailand. The failure of vector control to curtail the

spread of DENV-carrying mosquitos has further

intensified the need for vaccines as an additional

disease prevention tool.

“Vaccines are critical to our ability to control

[dengue]…, and I think studies have shown that, in

terms of cost-effectiveness, vaccines are probably

the most cost-effective means of controlling a

disease like dengue…, so we are going to have to

use them.”


“We all hope that we will soon have a tetravalent

vaccine that is effective against all four [DENV]

serotypes.”


“Today, dengue is in 124 countries around the

world, and Aedes aegypti, the primary vector, is

everywhere…, so we need a vaccine to help

reduce transmission.”


Within the dengue vaccine pipeline, experts

interviewed by GlobalData agreed that the live-

attenuated vaccines, led by Sanofi Pasteur’s CYD-

TDV and Takeda’s DENVax, offer the most clinical

and commercial potential over the duration of the

forecast period. However, KOLs also agreed that a

domestically-produced live-attenuated vaccine, TV-

003, will seize market share from CYD-TDV and

DENVax in Brazil due to its lower price point.

“I think we will see the data for Sanofi’s [Phase III

clinical studies of CYD-TDV] around October to

November [of 2014]. I think [the release of CYD-

TDV’s Phase III data] is going to be a major

milestone in dengue vaccine development.”


“I think the two leading [vaccines in clinical

development] are definitely Sanofi Pasteur’s live-

attenuated vaccine [CYD-TDV], and Takeda’s live-

attenuated vaccine [DENVax] is just behind

[Sanofi’s] in clinical development.”


“[Researchers at] Brazil’s Butantan Institute are a

step behind [Sanofi and Takeda], but when they

are able to produce the vaccine [TV-003] and

demonstrate its efficacy and safety, it will be a

cheaper vaccine in Brazil [compared with CYD-

TDV and DENVax]. Since they are working with

the government, it will definitely be the vaccine

used [in Brazil] once it is introduced.”


Despite the many challenges associated with

dengue vaccine development, KOLs interviewed

by GlobalData are optimistic that vaccines will

soon become a key component of the disease

prevention algorithm. Nevertheless, these experts

have also cautioned that vaccines must be



Executive Summary

leveraged in conjunction with novel vector control

tools and surveillance programs in order to

effectively reduce the global disease burden of

dengue.

“We are really in a fantastic opportunity of looking

at the solution of a disease in a very integrated

way. It would be a failure to see vaccines as the

panacea, as the one-bullet solution.”


“I feel we are coming into an exciting era where we

are going have a bunch of new tools to attack

dengue: vaccines, antiviral drugs, therapeutic

antibodies, new insecticides, and new mosquito

control approaches. We can use [these new tools]

in an integrated fashion to control dengue in

targeted [prevention] programs….I think it’s a new

way of thinking about how we can control dengue.”


“We should have a new insecticide or two [in the

next few years], and we should have biological and

genetic [vector control] approaches, such as the

Wolbachia and the sterile male, that we can use

and integrate with vaccines in a synergistic way.

With these tools, we can go into a community, into

city like Bangkok, Jakarta, or Manila, and actually

impact transmission by using these methods in an

integrated fashion.”


“From the 1970s to the present, when we have

seen this dramatic emergence of epidemic dengue

and the virus’ geographic spread, vector control

has failed. Going forward, however, I am really

excited because I think we have new tools

coming…that are going to allow us to use vector

control in [combination] with vaccines to impact

[dengue] transmission.”



Table of Contents


1 Table of Contents

1 Table of Contents ..................................................................................................................... 10

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 ......................................................................................................................... 27

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


Table of Contents


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 ..................... 52

4.6 Discussion ........................................................................................................................ 53

4.6.1 Epidemiological Forecast Insight ................................................................................... 53

4.6.2 Limitations of the Analysis ............................................................................................. 54

4.6.3 Strengths of the Analysis ............................................................................................... 55

5 Current Surveillance, Prevention, and Control Measures .......................................................... 56

5.1 Overview ........................................................................................................................... 56

5.2 Brazil ................................................................................................................................. 62

5.2.1 Surveillance and Diagnosis ........................................................................................... 62

5.2.2 Vector Control ............................................................................................................... 62

5.2.3 Immunization Recommendations and Infrastructure ...................................................... 63

5.3 India .................................................................................................................................. 65


5.3.2 Vector Control ............................................................................................................... 66


5.4 Mexico .............................................................................................................................. 69


Table of Contents



5.4.2 Vector Control ............................................................................................................... 70


5.5 Singapore ......................................................................................................................... 73


5.5.2 Vector Control ............................................................................................................... 74


5.6 Thailand ............................................................................................................................ 76


5.6.2 Vector Control ............................................................................................................... 77


6 Unmet Needs Assessment and Opportunity Analysis ............................................................... 80

6.1 Overview ........................................................................................................................... 80

6.2 Unmet Needs Analysis ...................................................................................................... 82

6.2.1 Unmet Need: Safe and Efficacious Vaccines................................................................. 82

6.2.2 Unmet Need: An Improved Understanding of Dengue Immunity.................................... 84

6.2.3 Unmet Need: Reliable Immunological Correlates of Protection ..................................... 84

6.2.4 Unmet Need: Country-Specific Immunization Program Preparedness ........................... 85

6.2.5 Unmet Need: Upgraded Vector Control and Surveillance Infrastructures ...................... 86

6.2.6 Unmet Need: Improved Diagnostic Tools ...................................................................... 87

6.2.7 Unmet Need: High-Quality Animal Models .................................................................... 88

6.3 Opportunity Analysis ......................................................................................................... 89

6.3.1 Opportunity: Develop a Single-Dose Dengue Vaccine ................................................... 89


Table of Contents


6.3.2 Opportunity: Further Elucidate the Role(s) of T Cells in Dengue Immunity .................... 89

6.3.3 Opportunity: Streamline Vaccine Development with Innovative Clinical Trial Design ..... 90

6.3.4 Opportunity: Partner with Public Health Stakeholders to Integrate Vaccines into

Multifaceted Dengue Prevention Programs .................................................................. 91

6.3.5 Opportunity: Establish Country-Specific Vaccine Launch Strategies ............................. 92

6.3.6 Opportunity: Leverage Diagnostics to Demonstrate Vaccine Effectiveness Post-

Licensure...................................................................................................................... 93

7 Research and Development Strategies ..................................................................................... 94

7.1 Overview ........................................................................................................................... 94

7.2 Technological Approaches to Vaccine Development ......................................................... 94

7.2.1 Vaccine Antigen Selection ............................................................................................. 94

7.2.2 Tetravalent Vaccine Construction .................................................................................. 96

7.3 Partnerships, Acquisitions, and Licensing Agreements ..................................................... 98

7.4 Clinical Trial Design ........................................................................................................ 100

7.4.1 Current Clinical Trial Design ........................................................................................ 100

7.4.2 Inclusion of Representative Patient Populations in Clinical Trials ................................ 103

7.4.3 Demonstration of Protective Efficacy ........................................................................... 103

7.4.4 Dengue Human Infection Model .................................................................................. 104

8 Pipeline Assessment............................................................................................................... 106

8.1 Overview ......................................................................................................................... 106

8.2 Live-Attenuated Vaccines in Clinical Development .......................................................... 111

8.2.1 CYD-TDV .................................................................................................................... 111

8.2.2 DENVax ...................................................................................................................... 119


Table of Contents


8.2.3 TV-003 ........................................................................................................................ 124

8.3 Other Vaccines in Clinical Development.......................................................................... 130

8.3.1 TDENV-PIV ................................................................................................................. 130

8.3.2 DEN-80E ..................................................................................................................... 132

8.4 Vaccines in Preclinical Development ............................................................................... 136

9 Pipeline Valuation Analysis ..................................................................................................... 138

9.1 Clinical Benchmarking of Key Pipeline Vaccines ............................................................. 138

9.2 Commercial Benchmarking of Key Pipeline Vaccines ..................................................... 140

9.3 Competitive Assessment ................................................................................................. 142

9.4 Top-Line Five-Year Forecast ........................................................................................... 144

9.4.1 Brazil ........................................................................................................................... 147

9.4.2 India ............................................................................................................................ 148

9.4.3 Mexico......................................................................................................................... 149

9.4.4 Singapore .................................................................................................................... 149

9.4.5 Thailand ...................................................................................................................... 150

10 Appendix................................................................................................................................. 151

10.1 Bibliography .................................................................................................................... 151

10.2 Abbreviations .................................................................................................................. 171

10.3 Methodology ................................................................................................................... 175

10.4 Forecasting Methodology ................................................................................................ 175

10.4.1 Vaccinated Patients..................................................................................................... 175

10.4.2 Vaccination Coverage Rates ....................................................................................... 176

10.4.3 Vaccines Included in Each Class................................................................................. 176


Table of Contents


10.4.4 Vaccine Launch Dates ................................................................................................ 176

10.4.5 General Pricing Assumptions ...................................................................................... 177

10.4.6 Individual Vaccine Assumptions .................................................................................. 178

10.4.7 Pricing of Pipeline Vaccines ........................................................................................ 181

10.5 Physicians and Specialists Included in this Study ........................................................... 184

10.6 About the Authors ........................................................................................................... 186

10.6.1 Analyst ........................................................................................................................ 186

10.6.2 Epidemiologist ............................................................................................................. 186

10.6.3 Therapy Area Director ................................................................................................. 187

10.6.4 Global Head of Healthcare .......................................................................................... 187

10.7 About GlobalData ............................................................................................................ 188

10.8 Disclaimer ....................................................................................................................... 188


Table of Contents


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 ....................................................................................................................... 51

Table 9: Routine Immunization Recommendations in Brazil, 2014 .................................................................. 64

Table 10: Routine Immunization Recommendations in India, 2014 ................................................................. 68

Table 11: Routine Immunization Recommendations in Mexico, 2014 ............................................................. 72

Table 12: Routine Immunization Recommendations in Singapore, 2014 ........................................................ 75

Table 13: Routine Immunization Recommendations in Thailand, 2014 ........................................................... 78

Table 14: Unmet Need and Opportunity in Dengue Vaccines ......................................................................... 82

Table 15: Acquisitions and Licensing Agreements in the Dengue Vaccine Market, 2014 ................................ 99

Table 16: Design of Selected Dengue Vaccine Clinical Trials ....................................................................... 101

Table 17: Dengue Vaccines – Clinical Development Pipeline, 2014 ............................................................. 107

Table 18: Comparison of Dengue Vaccine Classes in Clinical Development, 2014 ....................................... 110

Table 19: Product Profile – CYD-TDV .......................................................................................................... 114

Table 20: Efficacy Profile – CYD-TDV .......................................................................................................... 116

Table 21: Safety Profile – CTD-TDV ............................................................................................................ 117


Table of Contents


Table 22: CYD-TDV SWOT Analysis, 2014 .................................................................................................. 118

Table 23: Product Profile – DENVax ............................................................................................................ 121

Table 24: Efficacy Profile – DENVax ............................................................................................................ 122

Table 25: DENVax SWOT Analysis, 2014 .................................................................................................... 123

Table 26: Product Profile – TV-003 .............................................................................................................. 126

Table 27: Efficacy Profile – TV-003 .............................................................................................................. 127

Table 28: Safety Profile – TV-003 ................................................................................................................ 128

Table 29: TV-003 SWOT Analysis, 2014 ...................................................................................................... 129

Table 30: Product Profile – TDENV-PIV ....................................................................................................... 131

Table 31: TDENV-PIV SWOT Analysis, 2014 ............................................................................................... 132

Table 32: Product Profile – DEN-80E ........................................................................................................... 134

Table 33: Efficacy Profile – DEN-80E ........................................................................................................... 135

Table 34: DEN-80E SWOT Analysis, 2014................................................................................................... 136

Table 35: Dengue Vaccines – Innovative Vaccines in Preclinical Development, 2014 ................................... 137

Table 36: Clinical Benchmarking of Key Pipeline Vaccines ........................................................................... 139

Table 37: Commercial Benchmarking of Key Pipeline Vaccines ................................................................... 141

Table 38: Top-Line Sales Forecast ($m) for Dengue Vaccines, 2015–2020 .................................................. 144

Table 39: Key Events Impacting Sales for Dengue Vaccines, 2015–2020 .................................................... 146

Table 40: Dengue Vaccines Market – Drivers and Barriers, 2015–2020 ....................................................... 147

Table 41: Key Launch Dates ........................................................................................................................ 177


Table of Contents


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 ....................................................................................................................... 50

Figure 6: 5MM, Age-Specific Distribution of Reported Laboratory-Confirmed Dengue Cases, Men and Women,

Annual Average, 2009–2013 ........................................................................................................... 52

Figure 7: 5MM, Age-Standardized Incidence of Reported Laboratory-Confirmed Dengue Cases, All Ages,

Annual Average, 2009–2013 ........................................................................................................... 53

Figure 8: Competitive Assessment of Pipeline Dengue Vaccines, 2015–2020 .............................................. 143

Figure 9: Global Sales for Pipeline Dengue Vaccines by Country, 2015–2020 .............................................. 145



Introduction

2 Introduction

2.1 Catalyst

Over the last three decades, dengue has become the most important vector-borne infectious

disease in the world, with approximately 100 million cases and 21,000 deaths worldwide being

attributed to the dengue virus (DENV) each year. Given the absence of a marketed vaccine,

disease prevention and control efforts have emphasized the use of surveillance programs and

elimination of the virus’ mosquito vectors. The near-universal failure of these measures to curtail

transmission and reduce the disease burden across the global marketplace — which, for the

purposes of this report, comprises 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 DENVax, to revolutionize the

treatment and prevention paradigm. The following key factors will contribute to the evolution of the

dengue vaccine marketplace during the forecast period from 2015–2020:

The launch of the first live-attenuated dengue vaccines, particularly Sanofi’s CYD-TDV and

Takeda’s DENVax. These vaccines are expected to be heralded by physicians, public health

officials, and policymakers as a welcome relief to the growing global burden of dengue.

Dengue’s growing socioeconomic and public health burden will lead countries to push for

widespread immunization as a preventative measure. Specifically, the past failures of vector

control initiatives to curtail the spread of the Aedes aegypti mosquito have left a glaring void in

the prevention landscape, which will hasten the uptake of vaccines. GlobalData anticipates that

country-specific immunization recommendations and policy implementation will be an essential

metric for determining future vaccine uptake. This report provides a detailed, primary research-

driven analysis of dengue immunization policy at the country-level.

Formidable logistical and financial hurdles must be overcome in order to successfully

assimilate a novel vaccine into the immunization program infrastructure of developing nations.

Dengue vaccine developers must adopt a country-specific approach to planning for vaccine

adoption, as this strategy represents an attractive opportunity for positioning a vaccine for rapid

adoption in multiple countries once it receives regulatory approval. Key opinion leaders (KOLs)

also indicated that one of the most important issues that must be addressed pre-launch is

vaccine pricing, a factor that will heavily influence the rate and extent of uptake in low- and



Introduction

middle-income nations. Stakeholders must also take into account how vector control and

disease surveillance spending will influence a country’s ability to afford mass dengue

immunization programs.

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 their rivals.

Domestically-supplied vaccines — most notably, the Butantan Institute’s TV-003 in Brazil and

Panacea Biotech’s/Biological E’s TV-003 in India — will limit market growth due to their low

price relative to vaccines produced by privately-held foreign companies.

2.2 Related Reports

GlobalData (2013). PharmaPoint: HIV – Global Drug Forecast and Market Analysis to 2022:

Event-Driven Update, May, 2013, GDHC41PIDR

GlobalData (2013). PharmaFocus: Vaccine Adjuvants in Infectious Disease, May, 2013,

GDHC001PFR

GlobalData (2013). PharmaPoint: Pediatric Respiratory Syncytial Virus Prophylactics – United

States Drug Forecast and Market Analysis to 2022, April, 2013, GDHC102PIDR

GlobalData (2013). PharmaPoint: Dermatophytic Onychomycosis – United States Drug

Forecast and Market Analysis to 2022, June, 2013, GDHC101PIDR

GlobalData (2013). PharmaFocus: Market Access Strategies for Antibiotics Targeting

Multidrug-Resistant Gram-Negative Bacteria, August 2013, GDHC004PFR

GlobalData (2013). PharmaFocus: HIV – R&D Strategies Towards Cure and Prevention,

August 2013, GDHC003PFR

GlobalData (2013). PharmaPoint: Meningococcal Vaccines – Global Drug Forecast and Market

Analysis to 2022: Event-Driven Update, August 2013, GDHC61PIDR

GlobalData (2013). PharmaPoint: Seasonal Influenza Vaccines – Global Drug Forecast and

Market Analysis to 2022: Event-Driven Update, September 2013, GDHC67PIDR



Introduction

GlobalData (2014). PharmaPoint: Prophylactic Hepatitis B Virus Vaccines – Global Drug

Forecast and Market Analysis to 2022, January 2014, GDHC68PIDR

GlobalData (2014). PharmaPoint: Prophylactic Human Papillomavirus Vaccines – Global Drug

Forecast and Market Analysis to 2022, May 2014, GDHC84PIDR

GlobalData (2014). PharmaPoint: Hepatitis C Virus – Global Drug Forecast and Market

Analysis to 2022: Event-Driven Update, May 2014, GDHC001EPIDR

2.3 Upcoming Related Reports

GlobalData (2014). OpportunityAnalyzer: Genital Herpes – Opportunity Analysis and Forecasts

to 2018

GlobalData (2014). OpportunityAnalyzer: Sepsis – Opportunity Analysis and Forecasts to 2018

GlobalData (2014). PharmaPoint: Methicillin-Resistant Staphylococcus aureus – Global Drug

Forecast and Market Analysis to 2022


Appendix


10.7 About GlobalData

GlobalData is a leading global provider of business intelligence in the healthcare industry.

GlobalData provides its clients with up-to-date information and analysis on the latest developments

in drug research, disease analysis, and clinical research and development. Our integrated business

intelligence solutions include a range of interactive online databases, analytical tools, reports, and

forecasts. Our analysis is supported by a 24/7 client support and analyst team.

GlobalData has offices in New York, San Francisco, Boston, London, India, Korea, Japan,

Singapore, and Australia.

10.8 Disclaimer

All Rights Reserved.

No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any

form by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior

permission of the publisher, GlobalData.

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