Kalydeco’s Safety and Benefits Studied in CF Patients with Severe Lung Disease

Treatment with Kalydeco (ivacaftor) improved lung function, exercise capacity, and sweat chloride concentration in cystic fibrosis (CF) patients with severe lung disease, a small retrospective analysis shows.

The study, “Effectiveness of ivacaftor in severe cystic fibrosis patients and non‐G551D gating mutations,” was published in the journal Pediatric Pulmonology.

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene — the cause of CF — result in the production of a faulty CFTR protein, a “gate” protein that controls the movement of charged salts, such as chloride, in and out of cells. As a result, the mutations cause the “gate” to be stuck closed.

Kalydeco is an approved treatment developed by Vertex Pharmaceuticals that targets the underlying cause of CF in people with specific mutations. The therapy rescues the CFTR protein function by keeping the CFTR gate open longer.

However, since clinical trials for Kalydeco often exclude CF patients with severe lung involvement, the therapy’s effects in this patient population requires further analysis.

In the study, a team of researchers in Italy performed a retrospective observational analysis of 13 patients with CF (six males, mean age of 29 years) with severe lung disease who were treated with Kalydeco. Their access to the therapy was made possible through a compassionate use program in Italy. Patients carried non‐G551D gating mutations in the CFTR gene.

Ask questions and share your knowledge of Cystic Fibrosis in our forums.

Severe lung disease was defined as: a percent predicted forced expiratory volume in one second (ppFEV1, a measure of how much air can be exhaled in one second after a deep inhaled breath) of less than 40% in the six months before the analysis; or being on a lung transplant waiting list, or with a fast worsening trend of lung function.

Researchers analyzed clinical data, including measures of lung function, six minute walk distance test (6MWT, which assesses exercise capacity and endurance), weight, height, and a sweat test that measures the salt (chlorine) concentration in sweat, among other parameters. This data were collected one year before and after starting treatment with Kalydeco. Patients in the study received Kalydeco for an average of 320 days.

Results showed after one year of Kalydeco treatment, the mean ppFEV1 increased from 35.1% to 46.6%, corresponding to an absolute increase in lung function of 11.5%. Patients’ ability to walk also increased significantly, from 535.1 meters (585 yards) to 611.6 meters (686 yards), as measured in the 6MWT after one year of treatment.

Pulmonary exacerbations (the acute worsening of lung symptoms) were significantly lessened, dropping by a factor of two, from 57 exacerbations to 28 following a year of Kalydeco treatment. Moreover, 38.5% of the patients (five of the 13) were free from exacerbations during the year after starting Kalydeco.

Patients’ weight also had a marked increase, from 52.7 kg (116 pounds) to 55.6 kg (122 pounds), and the results of the sweat test showed that the sweat chloride concentration decreased significantly, from 99.5 mmol/L (millimoles per liter) to 39.3 mmol/L after one year of treatment, a value clearly below the 60 mmol/L threshold that is used for CF diagnosis.

Overall, the findings suggest that treatment with Kalydeco is safe and “resulted in clinically and statistically significant and sustained improvements in multiple parameters in patients with CF carrying non‐G551D gating mutations and severe lung disease, pointing out that drugs modulating CFTR can benefit patients with CF with severe lung disease,” the team concluded.