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Diseases

Stakeholder Opinions: Cystic Fibrosis - A pipeline full of hope

Healthcare

Publication Date March 2009
Publisher Datamonitor
Product Type Report
Pages 232
ISBN Number not applicable
Product Code DAT01724

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Summary

Introduction

With cystic fibrosis patients still dying prematurely and only two products currently approved for the treatment of this disease, the market is wide open for new entrants. Not only will novel symptomatic treatments and re-formulations lead to improved treatment paradigms, truly disease-modifying compounds are in late-stage development and will significantly change the market.

Scope

Disease background, segmentation and epidemiology of cystic fibrosis in the US and five major European countries

  • Summary of the drug classes currently used for the treatment of cystic fibrosis lung disease and cystic fibrosis-related pancreatic insufficiency
  • An overview of unmet needs, the cystic fibrosis pipeline and clinical trial design
  • In-depth outline of around 85 compounds studied for the treatment of cystic fibrosis by the pharmaceutical industry and academic institutes

Highlights

It is clear that, although cystic fibrosis only affects around 52,000 patients in the five major European countries and the US, the pipeline is highly active with over 50 pharmaceutical companies involved. As many as 13 of the compounds studied by the pharmaceutical industry are currently in late-stage development.

The promise of gene therapy has yet to materialize, and mutation specific correcting therapy is eagerly anticipated. There are at least four protein repair treatments in clinical development for three different classes of mutations, although it is likely that combination strategies are required in order to enhance their efficacy.

Disease-modifying treatments that are not mutation-specific include alternative chloride channel activators and epithelial sodium channel inhibitors. Compounds in the former class are furthest along in development; however, it is likely that a combination of the two classes will be necessary for full correction of the airway surface liquid.

Reasons to Purchase

  • Understand and capitalize on clinical unmet needs in the market through both lifecycle management of marketed drugs and new product development
  • Assess the cystic fibrosis pipeline both through background reading and via the interactive Excel-based pipeline summary
  • Identify physician awareness and perceptions surrounding future treatments and new developments for cystic fibrosis

Contents

  • ABOUT DATAMONITOR HEALTHCARE
    • About the Infectious Disease and Respiratory (ID&R) pharmaceutical analysis team
  • CHAPTER 1 EXECUTIVE SUMMARY
    • Scope of the analysis
    • Datamonitor insight into the cystic fibrosis market
    • Contributing experts
    • Related reports
  • CHAPTER 2 CYSTIC FIBROSIS DISEASE BACKGROUND
    • Overview of cystic fibrosis
    • The vicious cycle of obstruction, inflammation and infection
    • Cystic fibrosis patient segmentation
    • Segmentation by mutation: most patients suffer from a ?F508 mutation
    • Segmentation by bacterial colonization: Staphylococcus aureus and Pseudomonas aeruginosa are the most common bacterial infections in the cystic fibrosis lung
    • Segmentation by race: cystic fibrosis is most prevalent in Caucasians
    • Segmentation by gender: gender does not impact risk of cystic fibrosis
    • Segmentation by co-morbidities: diabetes and bone disease are most common co-morbidities
    • Epidemiology of cystic fibrosis
  • CHAPTER 3 DIAGNOSIS AND TREATMENT OF CYSTIC FIBROSIS
    • Diagnosis of cystic fibrosis
    • Clinical scoring systems in cystic fibrosis
    • Current treatment of cystic fibrosis
    • Mucolytics
    • Antibiotics
    • Anti-inflammatories
    • Pancreatic enzyme replacement therapy (PERT)
    • Nutritional supplements
    • Unmet needs in cystic fibrosis
    • Causative therapy of cystic fibrosis is on top of everyone's list
    • New antibiotics are needed to fight infections more successfully
    • Easier and less frequent drug administration may improve compliance
    • Lack of a cystic fibrosis animal model hampers preclinical development
    • More pediatric clinical trials are needed
  • CHAPTER 4 R&D APPROACH
    • The cystic fibrosis pipeline is highly active
    • Cystic Fibrosis Foundation plays an important role in the development of new drugs
    • Clinical trial design in cystic fibrosis
    • There are a limited number of cystic fibrosis patients available for clinical trials
    • Orphan drug status has certain advantages
    • Endpoints in cystic fibrosis clinical trials
  • CHAPTER 5 TREATMENTS THAT TARGET THE UNDERLYING CAUSES OF CYSTIC FIBROSIS
    • Gene therapies and gene manipulation
    • Viral vectors
    • Non-viral vectors
    • Gene therapies in clinical development
    • pGM169/GL67A (academic institutes)
    • DNA nanoparticles (Copernicus Therapeutics)
    • Gene manipulation therapies in early development
    • Late-stage gene therapies recently discontinued
    • Protein repair treatments
    • Protein repair treatments for class I mutations
    • Ataluren (PTC124, PTC Therapeutics/Genzyme)
    • Protein repair treatments for class II mutations
    • Miglustat (Actelion)
    • VX-809 (Vertex Pharmaceuticals)
    • Curcumin (Seer Pharmaceuticals)
    • Other protein repair treatments for class II mutations
    • Protein repair treatments for class III mutations
    • VX-770 (Vertex Pharmaceuticals)
    • Alternative chloride channel activators
    • Denufosol tetrasodium/INS37217 (Inspire Pharmaceuticals)
    • Duramycin (lancovutide, Moli1901, AOP Orphan Pharmaceuticals/Lantibio)
    • Other alternative chloride channel activators
    • Epithelial sodium channel (ENaC) inhibitors
    • QAU145 (Novartis)
    • 552-02 (Parion Sciences)
    • GS-9411 (Gilead Sciences/Parion Sciences)
    • INO-4995 (ISM Therapeutics)
    • Aerolytic (AER 002, Aerovance)
  • CHAPTER 6 TREATMENTS THAT TARGET INFECTIONS COMMON IN THE CYSTIC FIBROSIS LUNG
    • Antibiotics for the treatment of infections
    • Many new developments come in PARI Pharma's eFlow nebulizer
    • At least six direct competitors may threaten TOBI's monopoly in the near future
    • Aztreonam lysine (Gilead/PARI Pharma)
    • Marketing factors
    • Status update
    • Clinical trial data
    • Tobramycin (Novartis)
    • Tobramycin inhalation powder (TIP, Novartis/Nektar Therapeutics)
    • TOBI in the eFlow nebulizer (Novartis/PARI Pharma)
    • TOBI for young children (Novartis)
    • MP-376 (nebulized levofloxacin, Mpex Pharmaceuticals/PARI Pharma)
    • Cipro Inhale (dry powder ciprofloxacin, Bayer/Nektar Therapeutics)
    • GS 9310/11 (nebulized combination of fosfomycin and tobramycin, Gilead)
    • Liposomal formulations
    • ARD-3100 (ciprofloxacin, Aradigm/Tekmira Pharmaceuticals)
    • Arikace (TR-02/amikacin, Transave/PARI Pharma)
    • Antibiotics in early development
    • Zysolin (nanoparticle-encapsulated formulation of tobramycin, AlphaRx)
    • Bacteriophages (Biocontrol and MondoBiotech)
    • P113D (Demegen)
    • Panaecin (Gallium nitrate, Aridis Pharmaceuticals)
    • Academic institutes studying antibiotics
    • Intranasal tobramycin
    • Azithromycin
    • Linezolid
    • Itraconazole
    • Amiloride
    • Monoclonal antibodies for the treatment of bacterial infections
    • Aurexis (tefibazumab, Inhibitex)
    • KB001 (KaloBios)
    • Aerucin (Aridis Pharmaceuticals)
    • Immunization against bacterial infections
  • CHAPTER 7 TREATMENTS THAT TARGET THE MUCUS IN THE CYSTIC FIBROSIS LUNG
    • Mucolytics
    • Pulmozyme (Genentech)
    • Inhaled heparin as a mucolytic
    • VR496 (inhaled heparin, Vectura)
    • PGX-200 (inhaled heparin, ParinGenix)
    • Hyperosmolar agents
    • Bronchitol (mannitol, Pharmaxis)
    • Marketing factors
    • Clinical trial data
    • The Cystic Fibrosis Therapeutics Development Network is studying hypertonic saline in infants
  • CHAPTER 8 TREATMENTS THAT TARGET INFLAMMATION IN THE CYSTIC FIBROSIS LUNG
    • Nebulized alpha-1 antitrypsin therapy to target neutrophil elastase
    • AAT (nebulized alpha-1 antitrypsin, Kamada/PARI Pharma)
    • AZD9668 (AstraZeneca)
    • Respriva (nebulized alpha-1 antitrypsin, Arriva Pharmaceuticals)
    • Influencing airway inflammation by augmenting the nitric oxide pathway
    • INOmax (inhaled nitric oxide, Ikaria)
    • Pyruvate (N115, EmphyCorp)
    • Academic institutes studying compounds that augment the nitric oxide pathway
    • Nebulized L-arginine (The Hospital for Sick Children)
    • Pioglitazone (University of Southern California)
    • Simvastatin (University Hospitals of Cleveland and Akron's Children's Hospital)
    • AZD1236 (matrix metalloproteinase inhibitor, AstraZeneca)
    • Xolair (omalizumab, Novartis)
    • Other anti-inflammatory compounds in early development
    • SB656933 (IL-8/CXCR2 antagonist, GlaxoSmithKline)
    • Triolex (HE-3286, Hollis-Eden Pharmaceuticals)
    • Academic institutes studying other anti-inflammatory compounds
    • Antioxidants
    • Sildenafil (Viagra, University of New Mexico)
    • Digitoxin (FDA's Office of Orphan Products Development)
  • CHAPTER 9 OTHER APPROACHES TO TREATING CYSTIC FIBROSIS LUNG DISEASE
    • Aerosolized surfactant replacement therapy (Discovery Labs)
    • Spiriva (tiotropium, Boehringer Ingelheim)
    • RGN-457 (thymosin beta-4, RegeneRx Biopharmaceuticals)
    • Amitriptyline (University Hospital Tbingen)
  • CHAPTER 10 TREATMENTS THAT TARGET CYSTIC FIBROSIS-RELATED PANCREATIC INSUFFICIENCY
    • Pancreatic enzyme replacement therapies
    • Companies performing FDA-required clinical trials for marketed products
    • New pancreatic enzyme replacement therapies
    • Zentase (EUR-1008, Eurand)
    • Trizytek (ALTU-135, Cystic Fibrosis Foundation Therapeutics)
    • Exinalda (Biovitrum/AstraZeneca)
    • Nutritional supplements
    • Academics studying nutritional supplements
  • BIBLIOGRAPHY
    • Articles and reports
    • Datamonitor reports
    • Press releases
    • Websites
  • APPENDIX
    • Contributing experts
    • About Datamonitor
    • About Datamonitor Healthcare
    • Datamonitor Healthcare's therapy area capabilities
    • About the Disease analysis team
    • Disclaimer
  • List of Tables
    • Table 1: Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mutations by class
    • Table 2: Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mutation arrays by country
    • Table 3: Disease occurrence of cystic fibrosis per country in the seven major markets, 2004
    • Table 4: Epidemiology overview of cystic fibrosis in the six major markets, 2008
    • Table 5: Review of different cystic fibrosis scoring systems
    • Table 6: Overview of recent Cochrane reviews on the role of antibiotics in cystic fibrosis
    • Table 7: Reasons for poor compliance of cystic fibrosis patients with different treatments
    • Table 8: Age groups studied in Phase III trials for cystic fibrosis lung disease
    • Table 9: The five cystic fibrosis clinical trials currently ongoing or recruiting with the highest number of patients (expected to be) enrolled, 2009
    • Table 10: Advantages of orphan drug status in the US and Europe
    • Table 11: Outcome measures in clinical trials of cystic fibrosis patients
    • Table 12: Compounds that target the underlying cause of cystic fibrosis, 2009
    • Table 13: Rough estimate of the number of cystic fibrosis patients within each class of mutations, by country, 2009
    • Table 14: Overview of three Phase II trials for denufosol tetrasodium for the treatment of cystic fibrosis
    • Table 15: Antibiotics in clinical development by the pharmaceutical industry for the treatment of lung infections in cystic fibrosis, 2009
    • Table 16: Compounds in development in PARI Pharma's eFlow nebulizer, 2009
    • Table 17: Phase III clinical trial summary for aztreonam lysine in cystic fibrosis, 2009
    • Table 18: Overview of ongoing clinical trials with Transave's Arikace (liposomal amikacin) in cystic fibrosis
    • Table 19: Preclinical compounds in development for the treatment of lung infections in cystic fibrosis, 2009
    • Table 20: Antibiotics in development by academic institutes for the treatment of lung infections in cystic fibrosis, 2009
    • Table 21: Overview of clinical trials currently ongoing in academic institutes with azithromycin in cystic fibrosis
    • Table 22: Monoclonal antibodies in development for the treatment and or prevention of lung infections in cystic fibrosis, 2009
    • Table 23: Compounds that target the mucus in the cystic fibrosis lung, 2009
    • Table 24: Clinical trial summary for Pulmozyme in young children with cystic fibrosis
    • Table 25: Phase II clinical trial summary for Bronchitol (mannitol) in cystic fibrosis
    • Table 26: Overview of Phase III trials currently ongoing with Bronchitol in cystic fibrosis
    • Table 27: Compounds that target inflammation in the cystic fibrosis lung, 2009
    • Table 28: Overview of Phase I clinical trials currently ongoing with SB656933 in cystic fibrosis
    • Table 29: Overview of the top five pancreatic enzyme replacement products in the US, 2007
    • Table 30: Pancreatic enzyme replacement therapies in development for cystic fibrosis-related pancreatic insufficiency, 2009
    • Table 31: Phase III efficacy results of Trizytek in the US cohort
    • Table 32: Overview of nutritional supplements currently studied in cystic fibrosis by academic institutes
  • List of Figures
    • Figure 1: Median predicted survival age of cystic fibrosis patients in the US, 1985-2006
    • Figure 2: Several possible mechanisms explain the increased susceptibility of the cystic fibrosis lung to infections
    • Figure 3: Molecular consequences of mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene
    • Figure 4: Prevalence of the ?F508 Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mutation among cystic fibrosis patients, across Europe
    • Figure 5: Respiratory infections by age group in cystic fibrosis patients in the US, 2006
    • Figure 6: Age-specific prevalence of no, non-mucoid, and mucoid Pseudomonas aeruginosa from birth to age 16
    • Figure 7: Percentage of cystic fibrosis patients in the US with each co-morbidity, 2006
    • Figure 8: The cystic fibrosis diagnostic process for neonatal and newborn screening
    • Figure 9: Recommended general process for diagnosing cystic fibrosis in individuals not diagnosed via neonatal or newborn screening
    • Figure 10: Number of pipeline cystic fibrosis drugs by class and type of sponsor, 2009
    • Figure 11: Number of pipeline cystic fibrosis drugs by class and phase of development, 2009
    • Figure 12: Different approaches used over time with adenovirus vectors in cystic fibrosis gene therapy
    • Figure 13: Phase II design and primary outcomes of Ataluren (PTC124) in cystic fibrosis
    • Figure 14: Timeline of recent developments for denufosol tetrasodium in cystic fibrosis, October 2007-December 2008
    • Figure 15: PARI Pharma's eFlow nebulizer
    • Figure 16: Overview of new formulations of antibiotics in clinical development for cystic fibrosis, 2009
    • Figure 17: Timeline of recent developments of aztreonam lysine for cystic fibrosis, October 2006-February 2009
    • Figure 18: Cohorts in Phase I trial comparing TIP with TOBI, and the T326 dry powder inhaler used in this trial
    • Figure 19: Phase II design and primary outcome measure of fosfomycin/tobramycin for inhalation
    • Figure 20: Timeline of recent developments of Bronchitol for cystic fibrosis, October 2007-December 2008
    • Figure 21: Possible causes and effects of low exhaled nitric oxide in cystic fibrosis lungs
    • Figure 22: Price per standard unit of the top five pancreatic enzyme replacement therapies in the US, 2003-07
    • Figure 23: Timeline of recent developments of Zentase for cystic fibrosis-related pancreatic insufficiency, December 2007-February 2009
    • Figure 24: Timeline of recent developments of Trizytek for cystic fibrosis-related pancreatic insufficiency, June 2007-February 2009