Ivacaftor in cystic fibrosis: the first disease modifying agent

The exact magnitude of cystic fibrosis (CF) in India is not known, as it is often misrepresented and underdiagnosed. CF is caused by a mutation in the gene that encodes for the CF transmembrane conductance regulator (CFTR) protein whose dysfunction leads to multiorgan manifestations. Most CF mutations either reduce the number of CFTR channels at the cell surface or impair the channel function. Current treatments (mucolytics, antibiotics and anti-inflammatory agents) target the secondary effects of CFTR dysfunction and help to ameliorate the symptoms but do not address the basic defect of the disease. Ivacaftor is a first-in-class oral CFTR potentiator that increases the CFTR channel opening. In clinical trials, ivacaftor has shown improved pulmonary function, normalization of sweat chloride concentration, substantial weight gain as well as acceptable safety profile. The most frequent adverse effects associated with ivacaftor include headache, oropharyngeal pain, upper respiratory tract infection, nasal congestion, abdominal pain and nasopharyngitis. FDA has approved this agent for the treatment of CF in patients aged 6 years or older with at least one copy of the G551D mutation in the CFTR gene. Searches of medline, cochrane database, medscape, SCOPUS and clinicaltrials.org were made for terms like CFTR potentiator, cystic fibrosis, and ivacaftor. Relevant journal articles from last 5 years were chosen. [Int J Basic Clin Pharmacol 2012; 1(3.000): 225-229]