Table of Contents
EXECUTIVE SUMMARY
- Scope of the analysis
- Datamonitor insight into the cystic fibrosis market
- Contributing experts
- Related reports
CYSTIC FIBROSIS DISEASE BACKGROUND
- Overview of cystic fibrosis
- The vicious cycle of obstruction, inflammation and infection
- Cystic fibrosis patient segmentation
- Epidemiology of cystic fibrosis
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
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
TREATMENTS THAT TARGET THE UNDERLYING CAUSES OF CYSTIC FIBROSIS
- Gene therapies and gene manipulation
- Viral vectors
- Non-viral vectors
- Gene therapies in clinical development
- Gene manipulation therapies in early development
- Late-stage gene therapies recently discontinued
- Protein repair treatments
- Protein repair treatments for class I mutations
- Protein repair treatments for class II mutations
- Protein repair treatments for class III mutations
- 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)
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)
- Tobramycin (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
- Antibiotics in early development
- Academic institutes studying antibiotics
- Monoclonal antibodies for the treatment of bacterial infections
- Aurexis (tefibazumab, Inhibitex)
- KB001 (KaloBios)
- Aerucin (Aridis Pharmaceuticals)
- Immunization against bacterial infections
TREATMENTS THAT TARGET THE MUCUS IN THE CYSTIC FIBROSIS LUNG
- Mucolytics
- Pulmozyme (Genentech)
- Inhaled heparin as a mucolytic
- Hyperosmolar agents
- Bronchitol (mannitol, Pharmaxis)
- The Cystic Fibrosis Therapeutics Development Network is studying
hypertonic saline in infants
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
- 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
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 Tubingen)
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
- Nutritional supplements
- Academics studying nutritional supplements
BIBLIOGRAPHY
- Articles and reports
- Datamonitor reports
- Press releases
- Websites
APPENDIX
TABLES
- Table: Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)
mutations by class
- Table: Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mutation
arrays by country
- Table: Disease occurrence of cystic fibrosis per country in the seven
major markets, 2004
- Table: Epidemiology overview of cystic fibrosis in the six major markets,
2008
- Table: Review of different cystic fibrosis scoring systems
- Table: Overview of recent Cochrane reviews on the role of antibiotics in
cystic fibrosis
- Table: Reasons for poor compliance of cystic fibrosis patients with
different treatments
- Table: Age groups studied in Phase III trials for cystic fibrosis lung
disease
- Table: The five cystic fibrosis clinical trials currently ongoing or
recruiting with the highest number of patients (expected to be) enrolled, 2009
- Table: Advantages of orphan drug status in the US and Europe
- Table: Outcome measures in clinical trials of cystic fibrosis patients
- Table: Compounds that target the underlying cause of cystic fibrosis, 2009
- Table: Rough estimate of the number of cystic fibrosis patients within
each class of mutations, by country, 2009
- Table: Overview of three Phase II trials for denufosol tetrasodium for the
treatment of cystic fibrosis
- Table: Antibiotics in clinical development by the pharmaceutical industry
for the treatment of lung infections in cystic fibrosis, 2009
- Table: Compounds in development in PARI Pharma' s eFlow nebulizer, 2009
- Table: Phase III clinical trial summary for aztreonam lysine in cystic
fibrosis, 2009
- Table: Overview of ongoing clinical trials with Transave' s Arikace
(liposomal amikacin) in cystic fibrosis
- Table: Preclinical compounds in development for the treatment of lung
infections in cystic fibrosis, 2009
- Table: Antibiotics in development by academic institutes for the treatment
of lung infections in cystic fibrosis, 2009
- Table: Overview of clinical trials currently ongoing in academic
institutes with azithromycin in cystic fibrosis
- Table: Monoclonal antibodies in development for the treatment and or
prevention of lung infections in cystic fibrosis, 2009
- Table: Compounds that target the mucus in the cystic fibrosis lung, 2009
- Table: Clinical trial summary for Pulmozyme in young children with cystic
fibrosis
- Table: Phase II clinical trial summary for Bronchitol (mannitol) in cystic
fibrosis
- Table: Overview of Phase III trials currently ongoing with Bronchitol in
cystic fibrosis
- Table: Compounds that target inflammation in the cystic fibrosis lung, 2009
- Table: Overview of Phase I clinical trials currently ongoing with SB656933
in cystic fibrosis
- Table: Overview of the top five pancreatic enzyme replacement products in
the US, 2007
- Table: Pancreatic enzyme replacement therapies in development for cystic
fibrosis-related pancreatic insufficiency, 2009
- Table: Phase III efficacy results of Trizytek in the US cohort
- Table: Overview of nutritional supplements currently studied in cystic
fibrosis by academic institutes
FIGURES
- Figure: Median predicted survival age of cystic fibrosis patients in the
US, 1985 - 2006
- Figure: Several possible mechanisms explain the increased susceptibility
of the cystic fibrosis lung to infections
- Figure: Molecular consequences of mutations in the Cystic Fibrosis
Transmembrane Conductance Regulator (CFTR) gene
- Figure: Prevalence of the ΔF508 Cystic Fibrosis Transmembrane
Conductance Regulator (CFTR) mutation among cystic fibrosis patients, across
Europe
- Figure: Respiratory infections by age group in cystic fibrosis patients in
the US, 2006
- Figure: Age-specific prevalence of no, non-mucoid, and mucoid Pseudomonas
aeruginosa from birth to age 16
- Figure: Percentage of cystic fibrosis patients in the US with each
co-morbidity, 2006
- Figure: The cystic fibrosis diagnostic process for neonatal and newborn
screening
- Figure: Recommended general process for diagnosing cystic fibrosis in
individuals not diagnosed via neonatal or newborn screening
- Figure: Number of pipeline cystic fibrosis drugs by class and type of
sponsor, 2009
- Figure: Number of pipeline cystic fibrosis drugs by class and phase of
development, 2009
- Figure: Different approaches used over time with adenovirus vectors in
cystic fibrosis gene therapy
- Figure: Phase II design and primary outcomes of Ataluren (PTC124) in
cystic fibrosis
- Figure: Timeline of recent developments for denufosol tetrasodium in
cystic fibrosis, October 2007 - December 2008
- Figure: PARI Pharma' s eFlow nebulizer
- Figure: Overview of new formulations of antibiotics in clinical
development for cystic fibrosis, 2009
- Figure: Timeline of recent developments of aztreonam lysine for cystic
fibrosis, October 2006 - February 2009
- Figure: Cohorts in Phase I trial comparing TIP with TOBI, and the T326 dry
powder inhaler used in this trial
- Figure: Phase II design and primary outcome measure of
fosfomycin/tobramycin for inhalation
- Figure: Timeline of recent developments of Bronchitol for cystic fibrosis,
October 2007 - December 2008
- Figure: Possible causes and effects of low exhaled nitric oxide in cystic
fibrosis lungs
- Figure: Price per standard unit of the top five pancreatic enzyme
replacement therapies in the US, 2003 - 07
- Figure: Timeline of recent developments of Zentase for cystic
fibrosis-related pancreatic insufficiency, December 2007 - February 2009
- Figure: Timeline of recent developments of Trizytek for cystic
fibrosis-related pancreatic insufficiency, June 2007 - February 2009
|
Related Report
|
View Cart
