Cystic fibrosis approach appears safe, worthy of study

Investigators examined the safety and adverse event profile of VX-770, an investigational agent that improves the function of mutant cystic fibrosis transmembrane conductance regulator (CFTR) protein. They also looked for evidence that VX-770 is associated with improvement in CFTR-mediated ion transport and pulmonary status.

The 39 adult patients in the study had cystic fibrosis, a G551D mutation on at least 1 CFTR allele, and a forced expiratory volume in 1 second of 40% of predicted value. The study was conducted in 2 parts, using different patients in each part. Each patient received oral VX-770 every 12 hours at doses ranging from 25 mg to 250 mg or placebo for 14 or 28 days, depending on the part of the study.

Adverse events occurred with similar frequency in the study groups, few adverse events were severe, and no patient withdrew from the study. Investigators observed significant within-patient improvements in respiratory (nasal potential difference) and nonrespiratory (sweat chloride concentration) biomarkers of CFTR function, as well as improvements in lung function (spirometric assessment) in patients taking VX-770. They noted that these findings are consistent with improved CFTR ion-channel function (Accurso FJ, et al. N Engl J Med. 2010;363[21]:1991-2003).

Only about 5% of cystic fibrosis patients in the United States have the G551D mutation targeted by this experimental medication. Nonetheless, this is an exciting step: drug development directed by identification of a specific genetic mutation and an understanding of how that mutation affects the structure and function of CFTR protein. As this process is repeated for the more than 1,000 identified mutations of the CFTR gene (especially the most common mutations), more and more focused therapies will be developed. For cystic fibrosis and for many other diseases, this will be the basis of personalized medical therapy based on genotype rather than phenotype of the person's disease.

-Michael Burke, MD