Stakeholder Opinions: Vaccine adjuvants - uncertainties rule

Stakeholder Opinions: Vaccine adjuvants - uncertainties rule

Introduction

Adjuvants are coming increasingly into focus for vaccine developers since many novel split- and subunit vaccines are insufficiently immunogenic on their own. Adjuvants offer a solution: they can accelerate, enhance and prolong the immune response to vaccination but also enable the use of antigen-sparing formulations. This makes them an attractive option for prophylactic and therapeutic vaccines.

Scope

*In-depth analysis of key TLR-dependent and TLR-independent adjuvant candidates in clinical development

*Thorough assessment of key opportunities and risks for novel adjuvants

*Review of clinical trials and available data for adjuvants in development

*In-depth discussion of regulatory hurdles and strategic advice on how to overcome them

Highlights

In order to overcome the high regulatory barriers, adjuvant developers should focus on indications with high unmet need and no available vaccines. As safety and reactogenicity will be key factors in the FDA's evaluation of novel adjuvants, the barrier to approval of novel adjuvants is lower for therapeutic than for prophylactic indications.

Datamonitor sees combinations of immunostimulatory adjuvants with efficacious delivery systems as a promising approach, but hurdles to approval for these combinations will be higher than for single-component adjuvants. The future regulatory performance of GSK's AS04 will have a crucial impact on the prospects of such combination approaches.

Most available licensed adjuvants, such as alum and MF59, stimulate a strong Th2 response, making them unsuitable for a large number of indications requiring a CTL-mediated immune responses. Novel adjuvants could significantly improve the prospects of vaccine development in indications with a high unmet need, including cancer and tuberculosis.

Reasons to Purchase

*Review profiles and clinical data of key adjuvants both marketed and in clinical development and assess their future potential

*Gain insight into the current state of the vaccine adjuvant industry and its future chances and challenges

*Understand regulatory hurdles and develop strategies to maximize chances of approval for novel adjuvants

ABOUT DATAMONITOR HEALTHCARE
2

About the Infectious Diseases analysis team
2

CHAPTER 1 EXECUTIVE SUMMARY
3

Strategic scoping and focus
3

Datamonitor insight into the disease market
3

Related reports
6

Upcoming related reports
6

CHAPTER 2 THE VALUE PROPOSITION FOR VACCINE ADJUVANTS
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Why are adjuvants needed?
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Vaccination triggers a complex immune response cascade
8

Adjuvants have a key role in increasing the immunogenicity of vaccination
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Brief history of adjuvant development
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Adjuvants can be split into two groups, based on their dominant mechanism of action
21

For vaccine manufacturers, adjuvant development brings significant challenges
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CHAPTER 3 REGULATORY SITUATION FOR ADJUVANTS
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History - only four adjuvants have been approved in the seven major markets (7MM) so far
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Safety and reactogenicity of novel adjuvants will form the key part of the FDA's decisions about approval
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Several key considerations may facilitate gaining FDA approval for novel adjuvants
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CHAPTER 4 ADJUVANT PROFILES
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TLR-independent adjuvants - delivery systems
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Mechanism
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Alum
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Profile
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Efficacy and safety
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Datamonitor assessment
49

Oil-in-water emulsions
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MF59 (Novartis)
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Profile
51

Efficacy and safety
53

Datamonitor assessment
55

AS03 (GlaxoSmithKline)
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Profile
57

Efficacy and safety data
57

Datamonitor assessment
60

Advax (Vaxine Pty)
61

Profile
61

Partnerships and licensing deals
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Efficacy and safety data
63

Datamonitor assessment
64

Saponins/ISCOMs (immunostimulating complexes)
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QS-21
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ISCOMs
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Liposomes
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TLR-dependent adjuvants - immune potentiators
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TLR-agonists can trigger both innate and adaptive immunity
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Only few TLR types are targeted by vaccine adjuvants
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TLR9 agonists activate both innate and adaptive immunity
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TLR3 is a receptor for double-stranded RNA
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TLR4 agonists stimulate inflammation
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Flagellin is the only known TLR5 ligand
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A multitude of TLR-dependent adjuvant candidates are in clinical development
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MPL-based adjuvants
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AS01
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AS02
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AS04
86

RC-529 (Dynavax)
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Profile
90

Partnerships and licensing deals
91

Efficacy and safety data
92

Datamonitor assessment
93

Flagellin (VaxInnate)
93

Profile
93

Partnerships and licensing deals
95

Clinical and safety data
96

Datamonitor assessment
98

TLR-agonists (Idera Pharma/Merck & Co)
101

Profile
101

Partnerships and licensing deals
102

Clinical and safety data
105

Datamonitor assessment
106

CpG 7909 (Pfizer)
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Profile
106

Partnerships and licensing deals
107

Clinical data
110

Safety data
113

Datamonitor assessment
114

IC31 (Intercell)
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Profile
114

Partnerships and licensing deals
116

Clinical and safety data
117

Datamonitor assessment
119

ISS (Dynavax)
120

Profile
120

Partnerships and licensing deals
122

Efficacy and safety data
126

Datamonitor assessment
126

BIBLIOGRAPHY
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Literature
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APPENDIX
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Contributing experts
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Academic key opinion leaders
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Industry key opinion leaders
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Report methodology
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About Datamonitor
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About Datamonitor Healthcare
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About the Infectious Diseases analysis team
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Key therapy team members
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Holger Rovini, Head of Respiratory and Infectious Diseases
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Hedwig Kresse, Senior Analyst, Infectious Diseases
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Disclaimer
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List of Tables

Table 1: Key present and past links between Big Pharma and novel adjuvants
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Table 2: Key TLR-independent adjuvants in development for prophylactic vaccines
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Table 3: MF59: key facts, 2008
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Table 4: AS03: key facts, 2008
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Table 5: Advax: key facts, 2008
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Table 6: Advax - deals and alliances overview, 2008
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Table 7: TLR types, natural ligands and adjuvant strategies
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Table 8: Key TLR-dependent adjuvants in development for prophylactic vaccines, 2008
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Table 9: Key TLR-dependent adjuvants in development for therapeutic indications, 2008
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Table 10: AS01: key facts, 2008
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Table 11: AS02: key facts, 2008
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Table 12: AS04: key facts, 2008
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Table 13: RC-529: key facts, 2008
91

Table 14: RC-529 - deals and alliances overview, 2008
92

Table 15: Flagellin: key facts, 2008
95

Table 16: VaxInnate's TLR technology - deals and alliances overview, 2008
96

Table 17: TLR agonists (Idera): key facts, 2008
102

Table 18: Idera's TLR technology - deals and alliances overview, 2008
104

Table 19: CpG 7909: key facts, 2008
107

Table 20: CpG 7909 - deals and alliances overview, 2008
109

Table 21: IC31: key facts, 2008
115

Table 22: IC31 - deals and alliances overview, 2008
117

Table 23: ISS: key facts, 2008
121

Table 24: ISS technology - deals and alliances overview, 2008
125

List of Figures

Figure 1: Overview of immune responses after vaccination or infection
9

Figure 2: Promising indications for vaccine adjuvants
17

Figure 3: Milestones in adjuvant development
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Figure 4: Adjuvant classes used in marketed and pipeline vaccines
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Figure 5: Drivers and resistors for adjuvant development
29

Figure 6: Strategies to maximize chances for the FDA approval for novel adjuvants
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Figure 7: Efficacy of MF59-adjuvanted influenza vaccine versus non-adjuvanted influenza vaccine in elderly with or without underlying chronic disease
54

Figure 8: CpG 7909 - rapid seroconversion in combination with Engerix-B in healthy patients
111