Most people with cystic fibrosis have mutations in the CFTR gene that prevent sufficient quantities of the assembled channels from making it to the cell membrane surface. That's a hard problem to fix. However, a small minority (4-5%) have mutations on the G551D allele that impair the function of the CFTR ion channel once it makes it to the membrane. Ivacaftor (VX-770) is an oral drug that somehow helps CFTR channels at the cell membrane stay open.
Ramsey et al report results of a phase 3 clinical trial testing the VX-770 in cystic fibrosis patients over age 12 with the G551D CFTR mutation. They randomized 161 patients to receive either ivacaftor 150 mg b.i.d. or placebo for 48 weeks.
- Ivacaftor improved FEV1 percent predicted by an absolute 10.6 percentage points (e.g., 50% before, to 60.6% predicted after).
- Even better, those taking ivacaftor had 55% fewer exacerbations of cystic fibrosis.
- They also had better scores on quality-of-life questionnaires, gained an average of 6 pounds more than controls.
- There were no differences in adverse events; serious adverse events were less frequent in the ivacaftor group.
The improvements in lung function were sustained throughout the study and at its termination at 48 weeks.
Great news, for those patients with this particular mutation -- about 5% of the 70,000 people worldwide affected by cystic fibrosis, or around 3,500 people. The study was sponsored by Vertex Pharmaceuticals, who make the investigational drug VX-770.
Ramsey BW et al. A CFTR Potentiator in Patients with Cystic Fibrosis and the G551D Mutation. N Engl J Med 2011;365:1663-1672.