インフルエンザワクチン：流行病への脅威がこの分野を復活させる

Abstract

Overview

Introduction

The influenza vaccine market, sized at approximately $2.2 billion in 2006, yields many challenges. Demand is highly variable, and only large players are able to cope with the need for annual updates and the costly manufacturing process. However, driven by the increasing pandemic threat, the market is growing fast and predicted to more than double in size by 2016.

Scope

• Strategic analysis of the current influenza market across the US, Japan, France, Germany, Italy, Spain and the UK and of key companies in the sector
• Thorough assessment of underlying commercial and clinical influencers shaping the influenza vaccine market
• Patient-based forecasts for the influenza vaccine market taking into account recommended vaccination groups and coverage rates in the 7 major markets
• In-depth comparative analysis of both seasonal and pandemic influenza vaccine pipeline candidates and discussion of their future potential

Report Highlights

The demand for influenza vaccines is highly variable and the time window for the vaccination is limited to just a few months per year. This, in combination with the need for annual updates and the long planning cycles required due to the lengthy egg-based manufacturing process, makes the flu vaccine market a highly challenging sector.

The pandemic threat has acted as an important driver for the seasonal vaccine market. Rising public awareness of influenza has increased the demand for seasonal vaccination. Government funding provided for pandemic research is also benefiting seasonal vaccine development through technology transfer.

With Novartis' cell-based Optaflu currently awaiting EU approval and ProteinSciences' baculovirus-based FluBlØk in phase III, new production techniques available are shaping up to change market dynamics. Further advances include adjuvanted vaccines, and, in earlier development stages, DNA- and universal vaccine candidates.

Reasons to Purchase

• Review the clinical and commercial factors driving new product decisions in influenza vaccines and the strategies of key players in the market
• Gain insight through a patient-based forecast and a thorough analysis of the seasonal and pandemic influenza vaccine pipeline
• Understand where concerns, unmet needs and future opportunities lie by learning about the views of key influenza vaccine opinion leaders

Table of Contents

• About the Infectious Diseases Pharmaceutical Analysis team
• CHAPTER 1 EXECUTIVE SUMMARY
  • Scope of the analysis
  • Key metrics
• CHAPTER 2 EPIDEMIOLOGY
  • Incidence
  • Risk groups
  • Transmission and symptoms
  • Diagnosis
  • Virus subtypes
  • Prevention and treatment
    • Vaccination prevents influenza infection
    • Antivirals can provide symptom relief and accelerate recovery
  • Antigenic shift and drift
  • Seasonal influenza epidemics
  • Influenza pandemics
    • Recent pandemics - fearsome lessons
    • Current pandemic status - waiting for the wave
    • H5N1 - the next pandemic virus?
    • Pandemic scenario - dramatic outlook for public health and economy
    • Preparing for disaster - national and international pandemic planning
• CHAPTER 3 MARKET DEFINITION AND OVERVIEW
  • Market size and growth estimates
  • Current vaccine classes
    • Trivalent inactivated vaccines
    • Life-attenuated influenza vaccines
  • Vaccine manufacturing
    • Egg-based manufacturing is lengthy and inflexible
    • Cell-based manufacturing would offer big advantages
      • MDCK (Madin Darby Canine Kidney Cells)
      • Vero cells
      • Per.C6 cells
      • Although highly promising, cell culture-based manufacturing still needs further development
  • Influenza vaccine supply - a yearly gamble
    • The number of vaccine manufacturers is fluctuating
    • Manufacturing capacities are expanding, but still not sufficient to meet global needs
    • Manufacturing problems can have a dramatic impact - the Chiron case
    • Influenza vaccine demand fluctuates considerably and is hard to predict
      • Time shifts between supply and vaccination schedules lead to fading demand as the flu season progresses
      • Changes in recommendations and subjective perception of risk have a significant impact on demand
      • Vaccination coverage rates vary among countries
    • Complex distribution pathways can delay timely vaccine supply
  • Country analysis
    • US - actively encouraging increased vaccination and influenza research
      • Pull - enlarging the national market size
      • Push - supporting the entry of additional products and suppliers
    • EU5 - slowly waking up to the influenza challenge
      • A European Influenza Task Force could improve co-ordination between European countries and the industry
      • Flu vaccines are cheaper in Europe than in the US
      • Reimbursement policies favor risk groups
    • Japan - low awareness and distrust hamper vaccine uptake
      • Japan has a low vaccination coverage due to low awareness and unfavorable reimbursement rates
      • Pandemic preparedness is a central concern of the Japanese government
  • Unmet needs in influenza vaccines
    • Pandemic vaccines could moderate the impact of a flu pandemic
    • Extending of manufacturing capacities would guarantee sufficient vaccine supply
    • Adjuvants could lead to better efficacy of vaccines in the elderly and reduce the amount of antigen needed for immunization
    • Faster manufacturing techniques would make vaccine production more flexible
    • Universal vaccines could eliminate the need for yearly updates
    • Needle-free administration methods would make vaccination more convenient
• CHAPTER 4 CURRENT PLAYERS AND THEIR STRATEGIES
  • Overview
  • Sanofi pasteur - expanding market leadership
    • Current position
      • Fluzone (Vaxigrip)
    • Strategic development
      • Cell-culture-based manufacturing - high hopes for Per.C6
      • Capacity - leading the field
      • Adjuvants - falling behind?
      • Pandemic vaccines - first-to-market in the US?
      • Strategic outlook
  • Novartis Vaccines - recovering from Chiron' s failure
    • Current position
      • Fluvirin
      • Agrippal S1
      • Fluad
      • Begrivac
    • Strategic development
      • Expanding reach - acquisition of Chiron provided access to influenza vaccine market
      • Cell-culture-based manufacturing - first-to-market with Optaflu?
      • Capacity - new facilities in the US and Europe set to increase production
      • Adjuvants - MF59, a new paradigm?
      • Pandemic vaccines - Europe as stepping stone
      • Strategic outlook
  • GSK - the lucky third
    • Current position
      • Fluarix
      • FluLaval/Fluviral
    • Strategic development
      • Expanding reach - acquisition of ID Biomedical opens gate to the US market
      • Cell-culture-based manufacturing - lagging behind the competition
      • Capacity - acquisition of Wyeth' s Marietta facility set to speed up cell-based manufacturing
      • Adjuvants -acquisition of Corixa provides access to novel technologies
      • Pandemic vaccines - first and second generation candidates show promising prospects
      • Strategic outlook
  • MedImmune - new hope in pediatric treatment
    • Current position
      • FluMist
    • Strategic development
      • Expanding reach - positioning and market penetration as main issues
      • Cell-culture-based manufacturing - catching up with the giants
      • Capacity - fill/finish as critical bottleneck
      • Pandemic vaccines - joining forces with NIAID
      • Strategic outlook
  • CSL - preparing to enter the US market
    • Current position
      • Fluvax
    • Strategic development
      • Expanding reach - US launch likely in the near future
      • Capacity - doubling production for the US market
      • Pandemic vaccines - slim chances to match the competition
      • Strategic outlook
  • Solvay - failing to commercialize on Influvac TC
    • Current position
      • Influvac
      • Invivac/Inflexal V
    • Strategic development
      • Cell-culture-based manufacturing - Influvac TC loses competitive advantage due to manufacturing delay
      • Capacity - it' s all about cell-based production
      • Pandemic vaccines - projects still in early stages
      • Strategic outlook
• CHAPTER 5 PATIENT-BASED FORECAST ANALYSIS
  • patient-based forecasting model
  • Limitations of the patient-based forecasting model
• CHAPTER 6 R&D APPROACH
  • Classification of pipeline products
    • Seasonal influenza vaccines
    • Pandemic influenza vaccines
  • Clinical trial design in influenza vaccine studies
• CHAPTER 7 PIPELINE ANALYSIS SEASONAL INFLUENZA
  • Pipeline overview for seasonal influenza
    • Late-stage pipeline summary
    • Comparative assessment
    • Definition of current comparator therapy
      • Seasonal influenza vaccine gold standard: Fluzone
  • Optaflu (Novartis Vaccines)
    • Drug overview
    • Clinical trial data
      • Phase III trial (EU) - comparison of safety, tolerability and immunogenicity of influenza vaccines in adults and elderly
    • Patient potential
    • Marketing factors
    • Satisfaction of unmet needs
    • drug assessment summary
  • FluBlØk (Protein Sciences/UMN Pharma)
    • Drug overview
    • Clinical trial data
      • Phase II/III - immunogenicity and safety of trivalent recombinant baculovirus-expressed hemagglutinin influenza vaccine in healthy adults
      • Phase IIb - dose-related safety and immunogenicity of a trivalent baculovirus-expressed influenza-virus hemagglutinin vaccine in elderly adults
    • Patient potential
    • Marketing factors
    • Satisfaction of unmet needs
    • drug assessment summary
  • Flu Improved (GlaxoSmithKline)
    • Drug overview
    • Clinical trial data
      • Phase II trial (EU) - Study to evaluate the immunogenicity and the safety of an adjuvanted influenza vaccine candidate
    • Patient potential
    • Marketing factors
    • Satisfaction of unmet needs
    • drug assessment summary
  • Seasonal flu vaccines (Sanofi pasteur)
    • Flu Micro-Injection
    • Flu Infants
    • Flu vaccine - new formulation
  • FluInsure (GlaxoSmithKline)
    • Drug overview
    • Clinical trial data
    • Patient potential
    • Marketing factors
    • Satisfaction of unmet needs
    • drug assessment summary
  • Immunostimulant seasonal influenza vaccine (Iomai)
    • Drug overview
    • Clinical trial data
    • Patient potential
    • Marketing factors
    • Satisfaction of unmet needs
    • drug assessment summary
  • Late-stage pipeline vaccines developed outside the seven major markets
    • Influsome-Vac (NasVax)
    • LAIV (BioDiem, Nobilon)
  • Early-stage vaccines for prevention of seasonal influenza
    • DNA vaccines
      • PowderMed - Pfizer' s entry route into the vaccine business
    • Universal vaccines
  • Late-stage development compounds recently discontinued
    • InfluJect (Baxter) - an uncertain future
• CHAPTER 8 PIPELINE ANALYSIS PANDEMIC INFLUENZA
  • Pipeline overview for pandemic influenza
    • Late-stage pipeline summary
    • Comparative assessment
    • Definition of current comparator therapy
  • H5N1 vaccines
    • Sanofi pasteur
      • H5N1 influenza virus vaccine
    • GSK
      • Daronrix
      • H5N1-007
    • Novartis Vaccines
      • Focetria
    • Baxter
      • H5N1 pandemic vaccine
    • CSL
      • H5N1 Pandemic Vaccine
  • H9N2 vaccines
    • Novartis Vaccines
      • H9N2 pandemic vaccine
    • GSK
      • H9N2 pandemic vaccine
    • Crucell
      • H9N2 pandemic vaccine
  • H2N2 vaccines
    • GSK
      • H2N2 pandemic vaccine
  • Early-stage vaccines for prevention of pandemic influenza
• APPENDIX A - BIBLIOGRAPHY
• APPENDIX B
  • Limitations of IMS data
  • About
    • About Healthcare
  • Healthcare' s therapy area capabilities
    • About the Infectious Diseases analysis team
    • Key therapy team members
      • Holger Rovini, Head of Respiratory and Infectious Diseases
      • Hedwig Kresse, Associate Analyst, Infectious Diseases
    • Disclaimer
  • List of Tables
    • Table 1: Key influenza parameters for the seven major markets
    • Table 2: Companies developing cell-based manufacturing and US funding for cell culture development
    • Table 3: Current and future production capacity of key influenza vaccine manufacturers
    • Table 4: Influenza vaccination rates in the US, 2004
    • Table 5: Influenza vaccine catalog prices by manufacturer, US. 2005-06
    • Table 6: Influenza pandemic contracts announced to date
    • Table 7: Key needle-free influenza vaccine administration methods in development, 2007
    • Table 8: Acquisitions in the influenza vaccine space, 2005-06
    • Table 9: Fluzone dosages
    • Table 10: Fluvax dosages by age group
    • Table 11: Late-stage pipeline seasonal influenza, February 2007
    • Table 12: drug assessment parameters
    • Table 13: Fluzone (Sanofi pasteur) - product profile
    • Table 14: Fluzone formulations, 2006-07
    • Table 15: Fluzone - efficacy in children aged 6-24 months
    • Table 16: Optaflu (Novartis) - product profile
    • Table 17: Optaflu - clinical trial summary
    • Table 18: FluBlØk (Protein Sciences) - product profile
    • Table 19: FluBlØk - clinical trial summary
    • Table 20: Flu Improved (GSK) - product profile
    • Table 21: Flu Improved - clinical trial summary
    • Table 22: FluInsure (GSK) - product profile
    • Table 23: FluInsure - clinical trial summary
    • Table 24: Immunostimulant seasonal influenza vaccine (Iomai) - product profile
    • Table 25: Early-stage seasonal and universal influenza vaccines, February 2007
    • Table 26: Key DNA flu vaccines in development
    • Table 27: Recently discontinued late-stage influenza vaccines
    • Table 28: Pandemic influenza - late-stage pipeline overview
    • Table 29: H5N1 influenza virus vaccine (Sanofi pasteur) - product profile
    • Table 30: Daronrix (GSK) - product profile
    • Table 31: H5N1-007 (GSK) - product profile
    • Table 32: Focetria (Novartis) - product profile
    • Table 33: H5N1 pandemic vaccine (Baxter) - product profile
    • Table 34: H5N1 pandemic vaccine (CSL) - product profile
    • Table 35: H9N2 pandemic vaccine (Novartis) - product profile
    • Table 36: H9N2 pandemic vaccine (GSK) - product profile
    • Table 37: H9N2 pandemic vaccine (Crucell) - product profile
    • Table 38: H2N2 pandemic vaccine (GSK) - product profile
    • Table 39: Early stage pipeline pandemic influenza vaccines, February 2007
  • List of Figures
    • Figure 1: Drivers and restrictors in the influenza vaccine market
    • Figure 2: Influenza vaccine market size forecast (7MM), 2006-16
    • Figure 3: pipeline assessment summary - seasonal influenza vaccines
    • Figure 4: pipeline assessment summary - pandemic influenza vaccines
    • Figure 5: Global annual influenza disease burden
    • Figure 6: Population at high risk of influenza infection or influenza-associated complications
    • Figure 7: Influenza A virus: structure and electron micrograph
    • Figure 8: Antigenic drift versus antigenic shift
    • Figure 9: Recommended vaccination schedule and months of peak influenza activity, US 1976-2006
    • Figure 10: Development of a pandemic influenza virus
    • Figure 11: Overview over influenza pandemics in the 20th century
    • Figure 12: WHO and CDC classification systems for pandemic threat
    • Figure 13: Emergence of new Influenza A subtypes, 1977-2006
    • Figure 14: Cumulative number of confirmed human cases of avian Influenza A/(H5N1)
    • Figure 15: Spread of H5N1 in poultry, wild birds and humans, 1996-2006
    • Figure 16: Current spread of H5N1 in poultry and wild birds, January 2007
    • Figure 17: Geographical spread of influenza vaccine sales, 2006
    • Figure 18: Growth drivers of the flu vaccine market
    • Figure 19: TIV and LAIV - key common and differentiating factors
    • Figure 20: Steps of the influenza vaccine manufacturing process and involved stakeholders
    • Figure 21: Egg-based vaccine manufacturing
    • Figure 22: Comparative analysis of MDCK, Vero and Per.C6 cells
    • Figure 23: Vaccine providers for the US market, 2000-06
    • Figure 24: Vaccine manufacturers in the seven major markets, 2006
    • Figure 25: Global influenza vaccine manufacturing capacity, 1994-2006
    • Figure 26: Influenza vaccine manufacturing facilities, 2006
    • Figure 27: High-risk individuals recommended for flu vaccination, US. 2004-05
    • Figure 28: Chiron - share price in response to events, Aug 2004- May 2005
    • Figure 29: Expected, delivered and demanded influenza vaccine supply for the US, 2004-05 season
    • Figure 30: Influenza vaccine supply versus demand in the US, 1980-2006
    • Figure 31: Flu vaccine supply and demand in relation to population recommended for vaccination, US 2003-06
    • Figure 32: Supply versus demand in a typical flu season
    • Figure 33: Global influenza vaccination coverage, 2002-03 season
    • Figure 34: Drivers and restrictors for influenza vaccination
    • Figure 35: US influenza vaccine distribution network
    • Figure 36: Use of different providers for influenza vaccination, US, 2005-06
    • Figure 37: US government strategies to foster growth of the national flu vaccine market
    • Figure 38: US average prices per dose in multi-dose vials, TIVs, 2002-06
    • Figure 39: Unmet needs in influenza vaccines
    • Figure 40: Leading players in the influenza vaccine market, US and EU5, 2005
    • Figure 41: Sanofi pasteur - influenza vaccine strategy
    • Figure 42: Novartis Vaccines - influenza vaccine strategy
    • Figure 43: GSK - influenza vaccine strategy
    • Figure 44: MedImmune - influenza vaccine strategy
    • Figure 45: CSL - influenza vaccine strategy
    • Figure 46: Solvay - influenza vaccine strategy
    • Figure 47: Influenza vaccine clinical trial process
    • Figure 48: assessment of seasonal influenza pipeline vaccines
    • Figure 49: Fluzone - strengths and weaknesses
    • Figure 50: Comparison of seroprotection rates between Optaflu and Agrippal in EU Phase III trial, 2006
    • Figure 51: Optaflu - competitive positioning analysis for seasonal influenza, 2007
    • Figure 52: FluBlØk: - efficacy results of Phase IIb trial
    • Figure 53: FluBlØk - competitive positioning analysis for seasonal influenza, 2007
    • Figure 54: Flu Improved - competitive positioning analysis for seasonal influenza, 2007
    • Figure 55: FluInsure - competitive positioning analysis for seasonal influenza, 2007
    • Figure 56: Iomai' s immunostimulant seasonal influenza vaccine - competitive positioning analysis for seasonal influenza, 2007
    • Figure 57: Pandemic versus pre-pandemic vaccination strategy
    • Figure 58: drug assessment summary - pandemic influenza pipeline vaccines
    • Figure 59: competitive positioning analysis of H5N1 influenza virus vaccine (Sanofi pasteur) for pandemic influenza, 2007
    • Figure 60: competitive positioning analysis of Daronrix (GSK) for pandemic influenza, 2007
    • Figure 61: competitive positioning analysis of H5N1-007 (GSK) for pandemic influenza, 2007
    • Figure 62: competitive positioning analysis of Focetria (Novartis) for pandemic influenza, 2007
    • Figure 63: competitive positioning analysis of H5N1 pandemic vaccine (Baxter) for pandemic influenza, 2007
    • Figure 64: competitive positioning analysis of H5N1 pandemic vaccine (CSL) for pandemic influenza, 2007
    • Figure 65: competitive positioning analysis of H9N2 pandemic vaccine (Novartis) for pandemic influenza, 2007
    • Figure 66: competitive positioning analysis of H9N2 pandemic vaccine (GSK) for pandemic influenza, 2007
    • Figure 67: competitive positioning analysis of H9N2 pandemic vaccine (Crucell) for pandemic influenza, 2007
    • Figure 68: competitive positioning analysis of H2N2 pandemic vaccine (GSK) for pandemic influenza, 2007