FTI Background
Cystic Fibrosis
Cystic Fibrosis CF) affects approximately 30,000 people in the United States (US) and 100,000 worldwide. CF is the most common life shortening genetic disorder in Caucasians, with a median age of death of 26.1 years in the US. CF is an autosomal recessive disorder characterized by progressive, obstructive pulmonary disease. Patients with CF are particularly susceptible to pulmonary infections with bacterial pathogens such as Pseudomonas aeruginosa (PA), methicillin-resistant Staphylococcus aureus (MRSA), methicillin-sensitive Staphylococcus aureus (MSSA), and Stenotrophomonas maltophilia, as well as Burkholderia and Achromobacter species.
Rationale for Development of Fosfomycin/Tobramycin Inhalation Solution (FTI)
CURx is developing a broad spectrum combination antibiotic consisting of fosfomycin (a phosphonic acid antibiotic with activity against gram-positive and gram-negative bacteria) and tobramycin (an aminoglycoside with potent gram-negative activity) for treatment of patients with CF. This fosfomycin/tobramycin inhalation solution (FTI) consists of a 4:1 ratio (wt/wt basis) of fosfomycin and tobramycin (F:T).
Fosfomycin/tobramycin inhalation solution is a potential option for treatment of CF lung infections. FTI is rapidly bactericidal for a variety of gram-negative and gram-positive respiratory pathogens commonly isolated from patients with CF and demonstrates enhanced bactericidal activity relative to its individual components. Data from gene expression, time-kill, and inhibition of macromolecular biosynthesis studies suggest that one explanation for the enhanced in vitro activity of F:T (4:1 [wt/wt]) is a result of increased tobramycin uptake . Furthermore, FTI demonstrates a reduced frequency of development of resistance relative to fosfomycin or tobramycin alone. It is important to note that the dose of tobramycin in FTI is lower than that of the approved dose of inhaled tobramycin in TIS, thereby suggesting the potential of FTI to minimize aminoglycoside toxicity from repeated long-term exposure to tobramycin.
Gilead had carried out clinical studies on FTI through Phase 2 before licensing FTI to CURx. We are now initiating all activities required for Phase 3 development and product registration, including product manufacturing and the design of a clinical program for review by the FDA.
CURx Scientific Advisory Board
Patrick Flume, MD
Professor of Medicine and Pediatrics and Director of the Cystic Fibrosis Center, Medical University of South Carolina, Charleston
Felix Ratjen, MD, FRCP(C)
Division Chief Respiratory and HE Sellers Chair in Cystic Fibrosis, Hospital for Sick Children, University of Toronto, Toronto
John LiPuma MD
Professor of Pediatrics (specialization in Cystic Fibrosis)Univ. of Michigan, Ann Arbor, MI
Nicole Mayer Hamblett PhD
Associate Professor in the Department of Pulmonary Medicine at the Seattle Children’s Hospital and Univ. of Washington School of Medicine, Seattle and Co-Director of the Cystic Fibrosis Therapeutic Network Coordinating Center
D.R. (Dutch) VanDevanter, PhD
Case Western Reserve University School of Medicine, Cleveland, OH
Cystic Fibrosis CF) affects approximately 30,000 people in the United States (US) and 100,000 worldwide. CF is the most common life shortening genetic disorder in Caucasians, with a median age of death of 26.1 years in the US. CF is an autosomal recessive disorder characterized by progressive, obstructive pulmonary disease. Patients with CF are particularly susceptible to pulmonary infections with bacterial pathogens such as Pseudomonas aeruginosa (PA), methicillin-resistant Staphylococcus aureus (MRSA), methicillin-sensitive Staphylococcus aureus (MSSA), and Stenotrophomonas maltophilia, as well as Burkholderia and Achromobacter species.
Rationale for Development of Fosfomycin/Tobramycin Inhalation Solution (FTI)
CURx is developing a broad spectrum combination antibiotic consisting of fosfomycin (a phosphonic acid antibiotic with activity against gram-positive and gram-negative bacteria) and tobramycin (an aminoglycoside with potent gram-negative activity) for treatment of patients with CF. This fosfomycin/tobramycin inhalation solution (FTI) consists of a 4:1 ratio (wt/wt basis) of fosfomycin and tobramycin (F:T).
Fosfomycin/tobramycin inhalation solution is a potential option for treatment of CF lung infections. FTI is rapidly bactericidal for a variety of gram-negative and gram-positive respiratory pathogens commonly isolated from patients with CF and demonstrates enhanced bactericidal activity relative to its individual components. Data from gene expression, time-kill, and inhibition of macromolecular biosynthesis studies suggest that one explanation for the enhanced in vitro activity of F:T (4:1 [wt/wt]) is a result of increased tobramycin uptake . Furthermore, FTI demonstrates a reduced frequency of development of resistance relative to fosfomycin or tobramycin alone. It is important to note that the dose of tobramycin in FTI is lower than that of the approved dose of inhaled tobramycin in TIS, thereby suggesting the potential of FTI to minimize aminoglycoside toxicity from repeated long-term exposure to tobramycin.
Gilead had carried out clinical studies on FTI through Phase 2 before licensing FTI to CURx. We are now initiating all activities required for Phase 3 development and product registration, including product manufacturing and the design of a clinical program for review by the FDA.
CURx Scientific Advisory Board
Patrick Flume, MD
Professor of Medicine and Pediatrics and Director of the Cystic Fibrosis Center, Medical University of South Carolina, Charleston
Felix Ratjen, MD, FRCP(C)
Division Chief Respiratory and HE Sellers Chair in Cystic Fibrosis, Hospital for Sick Children, University of Toronto, Toronto
John LiPuma MD
Professor of Pediatrics (specialization in Cystic Fibrosis)Univ. of Michigan, Ann Arbor, MI
Nicole Mayer Hamblett PhD
Associate Professor in the Department of Pulmonary Medicine at the Seattle Children’s Hospital and Univ. of Washington School of Medicine, Seattle and Co-Director of the Cystic Fibrosis Therapeutic Network Coordinating Center
D.R. (Dutch) VanDevanter, PhD
Case Western Reserve University School of Medicine, Cleveland, OH