Drug Delivery Technology: Developing a New Generation of Vaccines

Summary

"Over the past year, excitement within the industry has been growing as companies start to recognize the potential of vaccines.New i nsights into immunobiology and delivery systems may allow the development of better vaccines and vaccines for a wider range of diseases than was previously possible. The market looks set to explode over the next 5-10 years as a raft of new products based on these new technologies are developed and launched." Dr Sara Sleigh

Vaccination is recognized as a cost-effective medical strategy. Vaccines, alongside antibiotics and improved hygiene standards, have been responsible for a steady decrease in morbidity and mortality from infectious diseases worldwide since their introduction early in the 20th century. Currently available vaccines prevent up to 3 million deaths each year and 750,000 children avoid serious disability. Despite this high level of success, almost 7 million children under 5 years old still die each year from infections.

Conventional vaccines have been based on live attenuated, or killed, viruses or bacteria, or recombinant proteins from these organisms. The design of live attenuated vaccines depended to some extent on serendipity and resulted in low success rates; both live attenuated and

killed vaccines require handling live pathogens and are associated with safety problems. Vaccines based on recombinant protein antigens are not highly immunogenic, proteins can be difficult to manufacture and may have stability issues.

Recent scientific advances have increased our understanding of immunobiology and now allow the more rational design of vaccines. These advances include new delivery technologies that will improve the safety and immunogenicity of traditional vaccines as well as introducing entirely new methods of vaccine delivery such as DNA vaccines. It is largely through the development of new delivery methods that companies are now aiming to tackle infectious diseases that have evaded vaccine manufacture in the past, develop vaccines for potential diseases related to bioterrorism and launch the new category of therapeutic vaccines.

Vaccines are a vibrant area of pharmaceutical development. The activity in the marketplace has grown steadily over the past few years and looks set to continue and increase in the near future. This report describes the role of new delivery technologies in this rapidly growing field.

Contents

• 1 The vaccine market: opportunities for novel delivery technologies
  • 1.1 Introduction
  • 1.2 Overview of the market
    • 1.2.1 Market size
    • 1.2.2 Key pharma players
    • 1.2.3 Key areas of vaccine development
  • 1.3 Product pipeline
• 2 Market drivers and opportunities for vaccine delivery technologies
• 3 Leading vaccine delivery companie
• 4 Immune potentiators and adjuvants
  • 4.1 Immune potentiators
    • 4.1.1 Pattern recognition receptors
    • 4.1.2 Case Study: VaxImmuneTM (Coley Pharmaceuticals
    • 4.1.3 Host-derived immune potentiators
    • 4.1.4 Case study: Oncophage (Antigenics
    • 4.1.5 Case study: ImmuFACTTM (Immutep
  • 4.2 Adjuvant delivery systems
    • 4.2.1 Alum
    • 4.2.2 Emulsions
    • 4.2.3 Case study: Stimulon (Antigenics
    • 4.2.4 Iscoms (immunostimulating complexes
    • 4.2.5 Liposomes
    • 4.2.6 Virosomes
    • 4.2.7 Virus-like particles (VLPs
    • 4.2.8 Case study: VLPs in therapeutic vaccines (Cytos Biotechnology
    • 4.2.9 Microparticles/nanoparticles
  • 4.3 Our opinion on adjuvant technologies
• 5 Delivering DNA vaccines
  • 5.1 Viral delivery methods
    • 5.1.1 Adenovirus vectors
    • 5.1.2 Case study: AdVac (Crucell
    • 5.1.3 Poxvirus vectors
    • 5.1.4 Case study: TroVax (Oxford BioMedica
    • 5.1.5 Alphavirus vectors
    • 5.1.6 Adeno-associated virus
    • 5.1.7 Other viral vectors
    • 5.1.8 Case study: ChimeriVaxTM (Sanofi Pasteur
    • 5.1.9 Case study: ImmunoVEX (BioVex
  • 5.2 Bacterial delivery methods
  • 5.3 Complexed DNA
    • 5.3.1 Case Study: cationic lipid delivery system VaxfectinTM (Vical Inc
  • 5.4 Delivery of uncomplexed DNA
    • 5.4.1 Case study: TriGridTM Delivery System (Ichor Medical Systems
    • 5.4.2 Case Study: PowderJect technology (PowderMed, part of Pfizer
  • 5.5 Our opinion on DNA vaccine delivery technologies
• 6 Vaccine delivery to the mucosal system and skin
  • 6.1 Intranasal and inhaled vaccine delivery
    • 6.1.1 Case study: polycationic liposomes (NasVax
    • 6.1.2 Case study: Modulation of Tight Junction Biology (Alba Therapeutics
  • 6.2 Oral vaccine delivery
    • 6.2.1 Case study: oral delivery with live bacterial vectors (Avant Immunotherapeutics
  • 6.3 Plant-derived vaccines
    • 6.4.1 Case study: the PassPortTM Patch (Altea Therapeutics
  • 6.5 Our opinion on mucosal and skin delivery technologies
• 7 Needle-free delivery
  • 7.1 Liquid jet injectors
    • 7.1.1 Case study: Biojector 2000 and VitaVax (Bioject Medical Technologies Inc
  • 7.2 Solid dose injectors
    • 7.2.1 Case study: Glide Pharmas' Solid Dose Injector
  • 7.3 Our opinion on needle-free delivery technologies
• 8 Single-dose vaccines
  • • 8.1.1 Case study: OctoVaxTM (OctoPlus
    • 8.1.2 Case study: stabilizing vaccines in glass microspheres (Cambridge Biostability
• 9 Market trends in drug delivery in vaccines
  • 9.1 Key vaccine delivery companies
  • 9.2 Recent partnerships and acquisitions
  • 9.3 Market trends 2006-2012
    • 9.3.1 Global vaccine delivery market 2006-2012
    • 9.3.2 Pharma drivers and vaccine delivery trends by 2012
  • 9.4 Market by 2020
    • 9.4.1 Global vaccine and vaccine delivery markets by 2020
    • 9.4.2 Pharma drivers and vaccine delivery trends by 2020
  • 9.5 Summary & Conclusions
• 10 Bibliography
• 11 Acknowledgements
• List of Tables:
• List of Figures:
  • Figure 1.1: Global vaccine market sales 2006
  • Figure 1.2: Leading vaccine brands 2006
  • Figure 1.3: Leading companies' vaccine sales (2006
  • Figure 1.4: Key areas of vaccine development
  • Figure 1.5: Numbers of vaccines in clinical development 2006
  • Figure 2.1: Schematic showing simplified mechanisms of humoral and cellular immune response
  • Figure 2.2: Vaccine delivery opportunities
  • Figure 4.1: Pathway of events following TLR9 activation by CpG oligonucleotides
  • Figure 5.1: Oxford BioMedica's therapeutic cancer vaccine TroVax
  • Figure 5.2: The TriGridTM Delivery System from Ichor Medical Systems
  • Figure 5.3: Schematic diagram of the PowderJect device configured for preclinical use
  • Figure 6.1: Nasal anatomy
  • Figure 6.2: Tight junction biology
  • Figure 6.3: Avant Immnotherapeutic's live bacterial vaccine vector
  • Figure 6.4: Use of the PassPortTM Patch and Applicator from Altea Therapeutics
  • Figure 7.1: Components of the Biojector 2000 device
  • Figure 7.2: Glide Pharmaceuticals Solid Dose Injector
  • Figure 9.1: Predicted influence of vaccine delivery technologies to 2020
• List of Tables:
  • Table 1.1: Anticipated vaccine sales as a percentage of overall pharma sales 2009 2012 for the top 5 companies
  • Table 1.2: Vaccines in clinical development
  • Table 3.1: Leading vaccine delivery companies
  • Table 4.1: Classification of vaccine adjuvants
  • Table 4.2: Pattern-recognition receptors
  • Table 4.3: Toll-like receptor agonists currently in development for vaccines
  • Table 4.4: Key characteristics of CpG ODNs
  • Table 4.5: Examples of current vaccine development programs with CpG ODNs
  • Table 4.6: Vaccines in development containing host-derived immune potentiators
  • Table 4.7: Virosome-based vaccines in development
  • Table 4.8: Advantages and disadvantages of VLP-based vaccines
  • Table 4.9: VLP-based vaccines for infectious disease
  • Table 4.10: Cytos Biotechnology development pipeline for VLP-based therapeutic vaccines
  • Table 5.1: Advantages and disadvantages of DNA vaccines
  • Table 5.2: Adenovirus-based vaccines in clinical development
  • Table 5.3: Licensees of Crucell's PER.C6 and AdVac technology
  • Table 5.4: MVA-based vaccines in development
  • Table 5.5: Alphavax vaccine development programs
  • Table 5.6: Other viral vectors under consideration for vaccine delivery
  • Table 5.7: ChimeriVaxTM products in clinical development
  • Table 5.8: GlobeImmune's product pipeline
  • Table 5.9: Vaccine candidates under development by Vical and its partners
  • Table 5.10: Companies developing electroporation devices for DNA vaccine delivery
  • Table 5.11: Pipelines of DNA vaccines delivered using electroporation
  • Table 5.12: PowderMed's vaccine pipeline
  • Table 6.1: Key companies advancing intranasal vaccine delivery
  • Table 6.2: Product pipelines of key companies advancing oral vaccine delivery
  • Table 6.3: Key companies developing vaccines for delivery through the skin
  • Table 6.4: Concealed mini-needle and micro-needle devices
  • Table 7.1: Examples of liquid jet injectors for needle-free vaccine delivery
  • Table 9.1: Summary of leading vaccine delivery companies
  • Table 9.2: Summary of recent alliances, agreements and acquisitions with vaccine delivery companies
  • Table 9.3: Forecasts of approved delivery driven vaccine products 2006-2012
  • Table 9.4: Forecasts of pipeline DD driven vaccine products 2006-2012 (US$ million)
  • Table 9.5: Forecast of vaccine delivery market 2012-2020 (US$ billion)