Cystic fibrosis · CFTR modulators
A CFTR potentiator in patients with cystic fibrosis and the G551D mutation
| Design | Randomised, double-blind, placebo-controlled trial |
|---|---|
| Treatment | Ivacaftor 150 mg twice daily |
| Control | Placebo |
| Population | Patients aged 12 and over with cystic fibrosis and at least one G551D-CFTR mutation |
| Follow-up | 48 weeks |
| Primary endpoint | Change from baseline in percentage predicted FEV1 through week 24 |
| Result | Percentage predicted FEV1 was 10.6 points higher with ivacaftor than placebo (p<0.001), evident by 2 weeks and sustained to 48 weeks. Pulmonary exacerbations were 55% less likely through week 48 (p<0.001). Respiratory symptom scores, weight and sweat chloride all improved substantially. |
| Secondary endpoints | Pulmonary exacerbations, respiratory symptoms, weight, sweat chloride |
Ivacaftor was associated with improvements in lung function at 2 weeks that were sustained through 48 weeks. Substantial improvements were also observed in the risk of pulmonary exacerbations, patient-reported respiratory symptoms, weight, and concentration of sweat chloride.
The trial authors, in the published abstract
The proof of principle for the whole modulator era, though G551D affects only about 4% of patients. The fall in sweat chloride is the striking part: a drug that measurably corrects the underlying channel defect, not the downstream disease. VX17-445-102 later brought that to the majority with Phe508del.
Ramsey BW, Davies J, McElvaney NG, et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med 2011 Nov 3;365(18):1663-72.