院内感染用ワクチンのパイプライン分析

Overview

Introduction

As the reimbursement status for the cost of hospital-acquired infections is under pressure by payors, interest in preventing these complications at the outset is growing. Nosocomial vaccines offer one route of prevention. This report assesses the clinical pipeline candidates five key nosocomial pathogens and their potential market environment including target population size estimates.

Scope

• In-depth analysis of epidemiology, spread, costs and reimbursement linked to nosocomial infections across the major Western markets
• Thorough general and pathogen-specific assessment of the market potential for the major 5 classes of nosocomial vaccines
• In-depth discussion and sizing estimates of potential target groups for nosocomial vaccines by pathogen
• Review of alternative strategies for infection prevention and comparison with vaccination

Report Highlights

The increasing incidence and severity of nosocomial infections has sparked an interest in preventive strategies such as vaccination. High costs and reimbursement cuts associated with nosocomial infections provide a strong incentive for healthcare stakeholders to invest in infection prevention, providing a strong rationale for vaccine development.

In the highly cost-conscious nosocomials market, a prudent definition of vaccination target groups will be crucial to satisfy the stringent cost-benefit analysis. Whereas patients undergoing planned hospital stays will benefit from vaccination, alternative prevention methods may be preferable for immuno-compromised, newborn and acute patients.

Datamonitor believes that C. difficile vaccines will have the easiest route to market due to the large and well-defined target population and a high unmet need. Vaccines against S. aureus and P. aeruginosa could prove valuable in selected target groups, whereas there is only a limited potential for vaccines against S. epidermidis and enterococcus.

Reasons to Purchase

• Review the epidemiological, clinical and economical factors driving new product decisions in nosocomial vaccine development.
• Gain insight into the pipeline through a discussion of key candidates in clinical development for five nosocomial pathogens.
• Understand and identify key market opportunities by reviewing sizing estimates for key target populations by pathogen.

• ABOUT DATAMONITOR HEALTHCARE
  • About the Infectious Diseases analysis team
• CHAPTER 1 EXECUTIVE SUMMARY
  • Objective of the analysis
  • Datamonitor insight into the nosocomial vaccines market
  • Contributing experts
  • Related reports
  • Upcoming related reports
• NOSOCOMIAL INFECTIONS - OVERVIEW OF EPIDEMIOLOGY AND KEYTARGETS FOR VACCINE DEVELOPMENT
  • Summary
  • Patients undergoing hospital stays face an elevated riskof infection
  • Nosocomial infections are a key health concern across the7MM
  • The risk of infection is highest in intensive care units
  • Nosocomial pneumonia and bloodstream infections have thehighest mortality rates
  • S. aureus, P. aeruginosa, S. epidermidis, enterococcus spp.and C. difficile are the most promising vaccine targets
• CHAPTER 2 FACTORS TO CONSIDER FOR THE ASSESSMENT OF THEOPPORTUNITY FOR NOSOCOMIAL VACCINES
  • Summary
  • A multitude of factors determine the market opportunityfor nosocomial vaccines
  • Costs associated with nosocomial infections vary betweentypes of infections
    • Multiple costs arise through nosocomial infections
    • Most costs are directly associated with the increasinglength of hospital stay
  • Reimbursement regulations for costs related to nosocomialinfections differ across the seven major markets
    • US - Medicare changes on the horizon increase thefinancial pressure on hospitals
      • Despite common belief, US hospitals lose money onnosocomial infections
      • Medicare will cut reimbursement for certain nosocomialinfections from October 2008
    • Japan' s prospective payment system needs further amendmentto incentivize hospitals effectively
    • Most major European markets operate DRG systems; however,levels of impact differ between countries
      • France
      • Germany
      • Italy
      • Spain
      • The UK
  • Various strategies exist for prevention and prophylaxis ofnosocomial infections
    • Antibiotic resistance and worse clinical outcome provide astrong rationale for prevention of nosocomial infections
    • There are three key approaches for prevention ofnosocomial infection aiming at different target populations
    • Hygiene and infection-control-based strategies
      • Advantages of hygiene and infection control strategiesinclude a significant reduction in infection rates and hospital costs
      • Disadvantages include lack of efficacy and problemsregarding implementation
      • Recommendations surrounding infection prevention varyacross the 7MM
    • Immunoglobulins
      • Fast protection and the chance to vaccinate patientsundergoing unplanned hospitalization are the key advantages ofimmunoglobulin-based strategies
      • Unclear efficacy along with limited tolerance and highcosts are key concerns linked to immunoglobulin-based preventionstrategies
      • Infections caused by staphylococci and Pseudomonas are themain focus of the nosocomial immunoglobulin pipeline
    • Vaccines
      • Long-lasting immunity is the key advantage of vaccinesover other methods of prophylaxis
      • Setbacks include efficacy and implementation ofvaccination in some key target populations
• CHAPTER 3 STAPHYLOCOCCUS AUREUS
  • Summary
  • Disease background - S. aureus causes a wide variety ofinfections, often initiated with commensal carriage of the pathogen
  • Treatment options - S. aureus resistance patternsdetermine the choice of drug
  • Resistance development - MRSA has become a crucial concernin both hospital and community
  • Epidemiology - elderly and surgical patients are theprincipal risk groups for S. aureus infection
    • Key risk groups
    • Epidemiology and spread of disease
  • Rationale for vaccine development - high incidence andincreasing resistance levels drive interest in vaccines
  • Market potential - a large population would be eligiblefor vaccination across the 7MM
    • Target population and market opportunity
      • Patients undergoing elective hospital operations
      • Dialysis
      • Elderly aged 65 years and over
      • Others
  • Pipeline - StaphVAX failure dampens hopes for rapid launchof a S. aureus vaccine
    • Summary
    • StaphVAX (Nabi Biopharmaceuticals)
      • Product profile
      • Clinical trial overview
      • Datamonitor assessment
    • V710 (Merck & Co/Intercell)
      • Product profile
      • Clinical trial data
      • Datamonitor assessment
    • SA75 (VRI plc)
      • Product profile
      • Clinical trial data
      • Datamonitor assessment
  • Assessment of the overall potential of S. aureus vaccines- good prospects, but significant challenges remain
• CHAPTER 4 STAPHYLOCOCCUS EPIDERMIDIS
  • Summary
  • Disease background - S. epidermidis is mainly associatedwith medical devices
  • Treatment options - many antibacterial drugs are activeagainst S. epidermidis
  • Resistance development - resistance levels arecomparatively low, but have been increasing
  • Epidemiology - patients undergoing implant surgery are atgreatest risk of infection
    • Key risk groups
    • Epidemiology and spread of disease
  • Rationale for vaccine development - protection against thenext potential "superbug"
  • Market potential - orthopedic, ophthalmic and cardiacsurgery patients would benefit most from vaccination
    • Target population and market opportunity
      • Implant and device surgery
      • Dialysis
  • Pipeline - no competition for Nabi
    • Summary
    • EpiVAX (Nabi Biopharmaceuticals)
  • Assessment of the overall potential of S. epidermidisvaccines - a combination vaccine with S. aureus is the way forward
• CHAPTER 5 PSEUDOMONAS AERUGINOSA
  • Summary
  • Disease background - P. aeruginosa causes a wide range ofdifferent infections
  • Treatment options - resistances set a limit on therapyapproaches
  • Resistance development - increasing non-response to alarge variety of drugs makes prevention a key interest
  • Epidemiology - P. aeruginosa is a critical pathogen in theICU
    • Key risk groups
    • Epidemiology and spread of disease
  • Rationale for vaccine development - resistance is the keydriver, but vaccine design will be challenging
  • Market potential - patients with severe respiratorydiseases and those at risk of an ICU stay are key target populations
    • Target population and market opportunity
      • Cystic fibrosis patients
      • Chronic obstructive pulmonary disease (COPD)
      • Patients undergoing planned surgery with subsequentpre-planned or highly likely ICU stay
      • Others
  • Pipeline - after many pipeline failures, IC43 lookspromising
    • Summary
    • IC43 (Intercell)
      • Product profile
      • Clinical trial data
  • Assessment of the overall potential for P. aeruginosavaccines
• CHAPTER 6 CLOSTRIDIUM DIFFICILE
  • Summary
  • Disease background - C. difficile causes severe diarrheaand colitis
  • Treatment - antibiotic drugs are available, but manypatients relapse
  • Resistance development - emergence of strain 027 isassociated with worse clinical outcomes
  • Epidemiology - the elderly are at greatest risk of C.difficile infection
    • Key risk groups
    • Epidemiology and spread of disease
      • The UK
      • The US
      • Germany
    • Economic burden
  • Rationale for vaccine development - high clinical need isthe key driver
  • Market potential - annual peak sales exceeding $1.5billion are realistic in the elderly population
    • Target population
    • Commercial opportunity
      • Initial market: people in institutionalized care
      • Long-term opportunity: vaccination of all people turning65
  • C. difficile vaccines pipeline - no competition forAcambis in sight
    • Summary
    • C. difficile vaccine (Acambis)
      • Product profile
      • Clinical trial data
      • Datamonitor assessment
  • Assessment of the overall potential for C. difficilevaccines - C. difficile is a highly promising target for nosocomialvaccination
• CHAPTER 7 ENTEROCOCCUS SPP.
  • Summary
  • Disease background - E. faecalis and E. faecium are keycauses of enterococcal infections
  • Treatment - resistances have limited the efficacy ofavailable antibiotic options
  • Resistance development - VRE is emerging as severe concern
  • Epidemiology - incidence and mortality of enterococcalinfections are increasing
    • Key risk groups
    • Epidemiology and spread of disease
  • Rationale for vaccine development
  • Market potential - it will be hard to construct a viablecost-efficacy case for enterococcal vaccination
    • Target population and commercial opportunity
  • Pipeline - no clinical candidates are developed forenterococcal infections yet
    • Summary
  • Assessment of the overall potential for enterococcalvaccines - alternative prevention strategies have better potential
• APPENDIX A
  • Bibliography
• APPENDIX B
  • Report methodology
  • About Datamonitor
    • About Datamonitor Healthcare
    • About the Infectious Diseases analysis team
    • Key therapy team members
      • Holger Rovini, Head of Respiratory and Infectious Diseases
      • Hedwig Kresse, Senior Analyst, Infectious Diseases
    • Disclaimer
• List of Tables
  • Table 1: Costs associated with nosocomial infections
  • Table 2: Antibodies against nosocomial infectionspipeline, March 2008
  • Table 3: S. aureus - Annual incidence estimates ofoverall elective hospital operations and key subtypes in the 7MM, 2008
  • Table 4: S. aureus - Annual incidence estimates ofdialysis in the 7MM, 2008
  • Table 5: S. aureus - elderly recurrent and totalpopulation sizes in the 7MM, 2008 (million)
  • Table 6: S. aureus vaccine pipeline, January 2008
  • Table 7: StaphVAX - product profile, 2008
  • Table 8: StaphVAX - end-stage renal disease trials,January 2008
  • Table 9: StaphVAX - orthopedic surgery trials, January2008
  • Table 10: StaphVAX - cardiovascular surgery trials, 2008
  • Table 11: StaphVAX - lot comparison trial, January 2008
  • Table 12: V710 - product profile, 2008
  • Table 13: V710 - clinical trial overview, January 2008
  • Table 14: SA75 - Product profile, 2008
  • Table 15: S. epidermidis - annual incidence estimates ofkey types of orthopedic/ophthalmic surgery in the 7MM, 2008
  • Table 16: S. epidermidis - annual incidence estimates ofkey types of cardiac surgery in the 7MM, 2008
  • Table 17: S. epidermidis - annual incidence estimates ofdialysis in the 7MM, 2008
  • Table 18: S. epidermidis vaccine pipeline, January 2008
  • Table 19: EpiVAX - Product profile, 2008
  • Table 20: P. aeruginosa - Annual incidence estimates ofcystic fibrosis in the 7MM, 2008
  • Table 21: P. aeruginosa - prevalence estimates ofdifferent stages of COPD in the 7MM, 2008
  • Table 22: Breakdown of patients at elevated risk of ICUstay (median hospital stay >7 days) by type of procedure and admissionin England, 2006
  • Table 23: Pseudomonas aeruginosa- total vaccinationtarget population sizes (7MM)
  • Table 24: P. aeruginosa vaccines - overview of keybacterial targets and candidates, 2008
  • Table 25: P. aeruginosa vaccines - clinical pipeline,January 2008
  • Table 26: Estimated incidence of C. difficile infectionsacross the 7MM
  • Table 27: C. difficile - total recurrent vaccinationtarget population sizes in the 7MM, 2008 (million)
  • Table 28: C. difficile - commercial opportunity andcost-efficacy estimate for vaccination in people undergoinginstitutionalized care in the 7MM, 2008
  • Table 29: C. difficile - commercial opportunity forannual and cumulative catch-up vaccination in all elderly aged 65 andolder in the 7MM, 2008
  • Table 30: C. difficile vaccine pipeline, January 2008
  • Table 31: C. difficile vaccine (Acambis) - productprofile, 2008
  • Table 32: Enterococcal vaccine pipeline, January 2008
• List of Figures
  • Figure 1: Number of deaths by leading cause of death inthe US, 2004
  • Figure 2: Nosocomial infections -most common types ofinfection in the US, 2007
  • Figure 3: Estimated number of healthcare-associatedinfections by subpopulation and major site of infection in the US, 2002
  • Figure 4: Rates of healthcare-associated infections bysubpopulation and major site of infection in the US, 2002
  • Figure 5: Origin of infection in ICU patients in the 5EU, 1992
  • Figure 6: Deaths associated with healthcare-associatedinfections in the US, 2002
  • Figure 7: Key ICU infections by causative pathogen inGermany, Spain, France, 2003/2005
  • Figure 8: Factors influencing the assessment of themarket opportunity for nosocomial vaccination in the 7MM, 2008
  • Figure 9: Nosocomial infections - additional days spentin hospital by type of infection
  • Figure 10: Hospital costs, reimbursement and losses forcentral-line BSI and pneumonia - Allegheny General Hospital in the US,2006
  • Figure 11: Drawbacks of antibiotic therapy andvalue-added of preventive strategies in nosocomial infections
  • Figure 12: Patient groups likely to benefit fromdifferent infection prevention strategies
  • Figure 13: Advantages and disadvantages of hygiene andinfection control-based strategies in the prevention and control ofnosocomial infections
  • Figure 14: Efficacy assessment of recommended preventivemeasures for the four most frequent types of nosocomial infection
  • Figure 15: Advantages and disadvantages ofimmunoglobulin-based strategies in the prevention and control ofnosocomial infections
  • Figure 16: Advantages and disadvantages of vaccinationstrategies in the prevention and control of nosocomial infections
  • Figure 17: MRSA - hospital discharges mentioning MRSA inthe US, 1993-2005
  • Figure 18: MRSA - hospital discharges per 100,000population by age group in the US, 2004
  • Figure 19: MRSA - prevalence among all S. aureusinfections in the 5EU, 1999-2006
  • Figure 20: MRSA -proportion of MRSA in ICUs versus otherhospital departments in the 5EU, 2006
  • Figure 21: MRSA - incidence in Japan, 1999-2005(sentinel reporting system)
  • Figure 22: S. aureus - incidence in the 5EU, 2001-06(sentinel reporting)
  • Figure 23: S. aureus - sizing estimates of key targetpopulations eligible for vaccination in the 7MM, 2008
  • Figure 24: Target group expansion model for S. aureusvaccination
  • Figure 25: S. aureus vaccine development - summary ofdrivers and resistors, 2008
  • Figure 26: S. epidermidis - sizing estimates of keytarget populations eligible for vaccination in the 7MM, 2008
  • Figure 27: S. epidermidis vaccine development - summaryof drivers and resistors, 2008
  • Figure 28: P. aeruginosa - antibiotic resistance levelsacross Europe, 2006
  • Figure 29: P. aeruginosa - bacteremia laboratory reportsin the UK, 1990-2004 (voluntary reporting)
  • Figure 30: P. aeruginosa - infections in Japan,1999-2005 (sentinel reports from ~470 hospitals)
  • Figure 31: P. aeruginosa - infections in ICUs inGermany, 2000 and 2005
  • Figure 32: P. aeruginosa - sizing estimates of keytarget populations eligible for vaccination in the 7MM, 2008
  • Figure 33: P. aeruginosa - potential annual cost savingsthrough vaccination in cystic fibrosis patients in the 7MM, 2003
  • Figure 34: P. aeruginosa vaccine development - summaryof drivers and resistors, 2008
  • Figure 35: C. difficile infection - course of disease
  • Figure 36: Age and sex distribution of C. difficilereports in the UK, January-December 2006 (voluntary surveillance)
  • Figure 37: C. difficile reports for patients aged 65years and over in the UK, 2000-06 (mandatory and voluntary reports)
  • Figure 38: Deaths related to C. difficile infection inEngland & Wales, 2001-06
  • Figure 39: C. difficile infections per 100,000 hospitaldischarges in the US, 1993-2003
  • Figure 40: Annual Clostridium difficile-relatedmortality rates per million population in the US, 1999-2004
  • Figure 41: C. difficile infections per 100,000in-hospital patients in Germany, 2000-04
  • Figure 42: C. difficile - possible target groupexpansion strategy for recurrent opportunity in the 7MM, 2008 (million)
  • Figure 43: C. difficile - market opportunity forvaccination in the 7MM, 2008
  • Figure 44: C. difficile vaccine development - summary ofdrivers and resistors, 2008
  • Figure 45: Vancomycin-resistant enterococci among ICUpatients in the US, 1995-2004
  • Figure 46: E. faecalis /E. faecium susceptibility tovancomycin in England and Wales, 1990-2005
  • Figure 47: E. faecium - vancomycin resistance in Europe,2001-06
  • Figure 48: Enterococcal infections by age group in theUK, 2005
  • Figure 49: Enterococcal bacteremia reports by type inthe UK, 2002-06
  • Figure 50: Enterococcal vaccine development - summary ofdrivers and resistors, 2008