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Potential of Denufosol as an Early Intervention Therapy for CF Lung Disease
Author(s) -
Navratil Tomas,
Schaberg Amy,
Tian Wei,
Durham Todd,
Evans Carole,
Lindroos Christina,
Barrus Susan,
Mathews Dave,
Barnes Matthew,
Ratjen Felix A.,
Moss Richard B.,
Accurso Frank J.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.31.9
Subject(s) - medicine , placebo , lung , disease , gastroenterology , activator (genetics) , pathology , receptor , alternative medicine
CF lung disease arises from ion transport defect. Disease origins in small airways before 1 yr of age necessitate early intervention. Denufosol (DEN), a novel chloride channel activator, stimulates Cl − transport, inhibits Na + absorption and increases ciliary beat frequency. A Phase 3, double‐blind, placebo (PL)‐controlled trial (TIGER‐1) was conducted in 352 CF pts to compare inhaled DEN 60 mg TID to PL for 24 wks. Pts were ≥ 5 yrs (mean 14.6 yrs) and had FEV 1 ≥ 75% predicted (mean 92%). Pulmonary function tests and exacerbations, QOL measures and systemic exposure of DEN were evaluated. This work examines endpoints relevant to DEN use as an early intervention agent. The ability to reach small airways was confirmed by significant improvement in FEF 25%–75% in pts ≤ 110% predicted FEV 1 (p=0.025). There was little to no systemic exposure to denufosol, no accumulation with chronic dosing, and no evidence of systemic AEs including liver enzyme levels, blood biochemistry and differential cell counts. DEN's mechanism of action addressing the basic defect, the lack of systemic exposure and ability to target small airways makes this a potentially promising therapy for early intervention in CF lung disease.