Stakeholder Opinions: Cystic Fibrosis - Big unmet needs, small steps

Abstract

Overview

Introduction

Overview of disease, current treatment options and future outlook for cystic fibrosis patients

Table of Contents

• ABOUT DATAMONITOR HEALTHCARE
  • About the Respiratory & Infectious Disease (RID)analysis team
• CHAPTER 1 EXECUTIVE SUMMARY
  • Scope
  • Datamonitor insight into the disease market
• CHAPTER 2 DISEASE BACKGROUND
  • Cystic fibrosis has a low prevalence, mainly concentratedin Caucasians
    • Cystic fibrosis affects mainly Caucasians
    • The cystic fibrosis population is aging
    • Gender does not play a significant role in the occurrenceof cystic fibrosis
    • Mortality is decreasing depending on age-group and genemutation
  • Etiology of cystic fibrosis
    • The chances of a child born with CF is 25% if both parentsare carriers of the mutated gene
    • Most common mutation inhibits chloride ion movement
    • Cystic fibrosis classifications can be based on symptoms,clinical history, chest X-rays, and/or genotypes
  • Cystic fibrosis symptoms affect several organs but havemost significant impact on the lungs
    • Bacterial pathogens play a key role in infection andinflammation of cystic fibrosis lungs
    • Thickening of mucus in pancreas and intestines leads tomaldigestion, malabsorption, and obstructions
    • Cystic fibrosis patients suffer from reproductive tractsymptoms
    • Skeletal symptoms are caused by nutritional problems andadverse effects of steroids
    • Liver symptoms due to obstruction may require livertransplant
    • Common co-morbidities include diabetes, bone disease andnasal polyps
• CHAPTER 3 DIAGNOSIS
  • Most cystic fibrosis sufferers are diagnosed by age three
    • Diagnosis of cystic fibrosis in adulthood is increasing
    • Cystic fibrosis patients diagnosed as adults enjoyimproved prognosis
  • Most important diagnostic test remains 40-year-old sweattest
    • Antenatal and neonatal screening is not always standard
    • Other tests can only confirm cystic fibrosis diagnosis
  • Diagnostic cystic fibrosis guidelines do not providesufficient detail
  • Diagnostic complications include late, mis- andunder-diagnosis
  • Current diagnostic tests offer opportunity for improvement
  • Factors influencing changes in diagnosis rates
• CHAPTER 4 TREATMENT OPTIONS
  • Mucolytics battle only symptoms
    • DNase
    • N-acetylcysteine (NAC)
    • Hypertonic saline
  • Antibiotics are mainstay treatment but cant entirelyclear infections
    • Difference between antibiotic therapy in CF patients andnon-CF patients lies in higher doses and longer treatment
    • Antibiotics used to treat infections in cystic fibrosis
  • Prescription of anti-inflammatories is contradictory toevidence
    • Corticosteroids
    • Non-steroidal anti-inflammatory drugs (NSAID)
    • Macrolides
    • Additional therapies with possible anti-inflammatoryeffects
  • Nutritional supplements focus on enzymes and vitamins
  • Physiotherapy is most important non-pharmacologicaltherapy
  • Oxygen therapy and surgery are last resorts
  • Most physicians rely on center-specific treatmentguidelines
  • Patient-compliance is key barrier to many treatmentoptions
• CHAPTER 5 FUTURE TRENDS
  • Ion channel therapy is the only promise in the pipeline
    • Gene therapy is in the far future
    • P. aeruginosa vaccines might provide valuable adjuncttherapy
• CHAPTER 6 REFERENCES
• APPENDIX 1 OPINION LEADER AND STAKEHOLDER TRANSCRIPTS
  • UK opinion leader
  • UK opinion leader
  • US opinion leader
  • German opinion leader
  • Disclaimer
• List of Tables
  • Table 1: Disease occurrence of cystic fibrosis in 2004,per country
  • Table 2: Incidence of cystic fibrosis mutations in theYorkshire population (UK)
  • Table 3: The severity of disease in cystic fibrosispatients in a pediatric and an adult center, according their lung function
  • Table 4: The modified Chrispin-Norman chest radiographscoring system for cystic fibrosis lung disease
  • Table 5: The Shwachman score for cystic fibrosisseverity classification
  • Table 6: Percentage of patients with co-morbiditiesaccording to key opinion leaders from a pediatric and an adult CF center,and the CFF Patient Registry (2004)
  • Table 7: Age of cystic fibrosis diagnosis in a pediatricand an adult CF center
  • Table 8: Cystic fibrosis pipeline overview, Phase III toPhase I, 2006
  • Table 9: Cystic fibrosis gene therapy pipeline overview,Phase II to Phase I, 2006
• List of Figures
  • Figure 1: There is variance in ethnic group epidemiologyof CF in the US
  • Figure 2: The percentage of adult cystic fibrosispatients is rising
  • Figure 3: Cystic fibrosis occurs at a similar rate inboth genders
  • Figure 4: Survival of cystic fibrosis patients has beenincreasing since 1980
  • Figure 5: Cystic fibrosis mortality has decreasedbetween 1985 and 1996 with highest benefit for 6-10 year old patients
  • Figure 6: When both parents carry the mutated gene, thechance of a child with cystic fibrosis is 25%
  • Figure 7: CFTR mutation inhibits chloride ion movement
  • Figure 8: Classification of cystic fibrosis lung diseasebased on FEV1 % predicted
  • Figure 9: Functional classification of CFTR alleles
  • Figure 10: CFTR function determines disease severity
  • Figure 11: The most important symptoms of cysticfibrosis are respiratory symptoms
  • Figure 12: The vicious cycle of obstruction,inflammation and infection in cystic fibrosis lungs
  • Figure 13: Median percent predicted FEV1 decreases ascystic fibrosis patients get older
  • Figure 14: Severity of cystic fibrosis lung diseasediffers for children and adults
  • Figure 15: There are several possible mechanisms thatexplain the increased susceptibility of cystic fibrosis lungs to pulmonaryinfection
  • Figure 16: Diverse bacterial infections colonize cysticfibrosis patients at different ages (US, 2004)
  • Figure 17: P. aeruginosa and S. aureus are most commonbacterial infections (US, 2004)
  • Figure 18: Co-morbidities increase when cystic fibrosispatients become older
  • Figure 19: Most cystic fibrosis patients are diagnosedby age three
  • Figure 20: Establishing the diagnosis of CF comprises ofseveral criteria
  • Figure 21: Diagnostic algorithm, 2003
  • Figure 22: Diagnosis of cystic fibrosis is discussedsuperficially in the "Standards of care" (CF Trust, 2001)
  • Figure 23: Overview of cystic fibrosis treatment options
  • Figure 24: Mucolytics
  • Figure 25: Antibiotics
  • Figure 26: Anti-inflammatories
  • Figure 27: Anti-inflammatory drugs and antibioticsinfluence vicious cycle in different ways
  • Figure 28: Macrolides could theoretical alter cysticfibrosis disease progress in different ways
  • Figure 29: Physiotherapy in cystic fibrosis focuses onthree main areas
  • Figure 30: Number of people with cystic fibrosis whoreceived lung transplants increased between 1992 and 2004 (US)
  • Figure 31: Adjusted patient survival after lungtransplant* in cystic fibrosis patients decreases every year (US, 2004)
  • Figure 32: Percentages of children who met some of theguidelines* in 2004 is higher than percentages of adults
  • Figure 33: Comparison of current and future cysticfibrosis therapies highlights the lack of a cure in the short term
  • Figure 34: Most projects in the cystic fibrosis pipelineare antibiotics or enzymes and are in Phase II
  • Figure 35: Gene therapy tgAAVCF by Targeted Geneticfailed in early 2005
  • Figure 36: Aerugen splits the antigenic O-polysaccharidewhich is transferred to exotoxin A