Pipeline and Commercial Insight: Influenza Vaccines - Pandemic threat revitalizes the sector

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