#NACFC2016 – Orkambi Therapy in Certain CF Patients Shows Long-term Lung Function Benefits

Cystic fibrosis (CF) patients carrying the F508del mutation in both CFTR gene copies maintained their lung function during more than two years of treatment with the combination drug Orkambi (ivacaftor/lumacaftor). The treatment also lowered the risk of acute exacerbations and improved patients’ weight.

The study, “Reduction in Rate of FEV1 Decline & Sustained Benefits w/Lumacaftor/Ivacaftor in Patients Aged ≥12 w/ CF Homozygous for F508del,” was presented at the 30th Annual North American Cystic Fibrosis Conference (NACFC) Oct. 27-29 in Orlando, Florida, during the “Clinical Advances in Cystic Fibrosis Research” session.

The PROGRESS trial was an extension study for patients who had participated in the earlier TRAFFIC (NCT01807923) and TRANSPORT (NCT01807949) studies of cystic fibrosis patients ages 12 or older. The initial trials explored the combination treatment for 24 weeks, and data from the additional 96 weeks of treatment in PROGRESS allowed researchers to analyze data for a continuous 120 weeks of treatment.

The main goal of the study was to investigate the safety of long-term treatment, but researchers could also analyze its effectiveness. Patients who had received active treatment during the first trials continued on the same doses, while those previously receiving a placebo were randomized to get one of two doses of the combination treatment.

At the meeting, researchers only reported data from patients treated with the approved dose of 400 mg lumacaftor and 250 mg Kalydeco every 12 hours.

Since the trial did not include placebo-treated controls, researchers compared data on lung function decline among participants, with values among patients homozygous for F508del in the U.S. CFF Patient Registry. Lung function was measured using forced expiratory volume during 1 second (FEV1).

A total of 340 patients were treated for 120 weeks or more, and 176 patients who were in the placebo group in the TRAFFIC or TRANSPORT trials received Orkambi for at least 96 weeks in the PROGRESS trial.

Side effects of the therapy were similar to what had been reported in the earlier trials, including difficulty breathing, cough, increased sputum, increase in blood pressure, and more. Respiratory adverse events most often occurred during the first week of treatment.

Researchers found that Orkambi decreased the estimated annual rate of lung function decline by 42 percent compared with controls; patients who received Orkambi had an annual rate of lung function decline of -1.33 percentage points per year, compared to -2.29 percentage points in the control group.

“These data suggest that the benefits of lumacaftor/ivacaftor are sustained through 96 weeks and indicate that the medicine may modify the progression of CF lung disease by treating its underlying cause,” Michael W. Konstan, MD, principal investigator of the study, vice dean for translational research at Case Western Reserve University School of Medicine and vice chair for clinical research at University Hospitals Rainbow Babies & Children’s Hospital, said in a press release.

The study was sponsored by Vertex Pharmaceuticals.