A drug for fixing a crucial defective protein in cystic fibrosis improved patients' lung function and sweat chloride levels, according to early results from a small randomized study.
The investigational oral drug, VX-770, is still in phase II trials. But preliminary findings in 20 patients—particularly the impact on sweat chloride levels—are drawing cautious optimism.
“These [results] are an extraordinary endorsement of our hypothesis—that small molecules can correct the basic defect and affect the clinical indicators of cystic fibrosis,” said Robert J. Beall, Ph.D., president and CEO of the Cystic Fibrosis Foundation, in a statement.
VX-770 targets defective Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) proteins in sweat duct epithelial cells. Dysfunctional CFTR proteins are believed to cause the fluid and salt imbalance that characterizes CF patients' airways.
The first part of the phase IIa trial included 20 patients who carry the G551D mutation in the CFTR gene. About 4% of CF patients in the United States carry the G551D mutation. Patients participated in two 14-day treatment periods. In addition to standard CF therapies, they received either placebo or one of three VX-770 dosage levels during each 14-day period.
At the end of 14 days, patients who received the highest dose of VX-770 (150 mg twice daily) experienced an average 10.1% increase in forced expiratory volume in 1 second (FEV1), compared with an average FEV1 decrease of less than 1% in placebo patients.
For patients on high-dose VX-770, sweat chloride levels fell from an average 95.5 mmol/L at baseline to 53.2 mmol/L after 14 days of treatment. Patients on placebo had no significant change in sweat chloride levels. Sweat chloride levels for CF patients typically are greater than 60 mmol/L, compared with normal values of less than 40 mmol/L in people without CF. The adverse events rate was similar between the groups. One patient had two serious adverse events, which researchers deemed were not related to VX-770.
The second stage of the drug's phase IIa trial is slated to begin later this year, and will enroll 16 patients for 28 days of randomized, placebo-controlled treatment. A phase IIb trial may begin in 2009, said the foundation. Vertex Pharmaceutical Inc. is developing VX-770 and a second compound, VX-809, with funding support from the Cystic Fibrosis Foundation.