A post-hoc analysis of the Phase 3 RECAP trial shows that long-term treatment with Esbriet (pirfenidone) is safe and similarly effective in patients with advanced idiopathic pulmonary fibrosis (IPF) as in those with less advanced disease.
The study, “Effect of pirfenidone in patients with more advanced idiopathic pulmonary fibrosis,” was published in the journal Respiratory Research.
Esbriet, marketed by Genentech, is a small molecule that halts the uncontrolled deposition of collagen fibers that lead to the destruction of healthy lung tissue.
Patients with more advanced IPF are usually excluded from clinical trials testing Esbriet — such as the Phase 3 ASCEND (NCT01366209), and the CAPACITY 1 (NCT00287729) and CAPACITY 2 (NCT00287716) trials.
Patients who completed any of these trials were allowed to participate in the Phase 3 RECAP (NCT00662038) study assessing Esbriet’s safety and efficacy (administered in doses of 2,403 mg per day). There were no restrictions on disease severity for entry into the RECAP trial, and the study included both patients with less and more advanced disease as assessed by two measures of lung function: forced vital capacity (FVC) and carbon monoxide diffusing capacity (DLco).
In the post-hoc analysis of the RECAP study, researchers evaluated the therapy’s efficacy and safety in patients with more advanced IPF — defined as a predicted FVC of less than 50%, and/or DLco less than 35% — and those with less advanced disease, with predicted FVC equal or higher than 50%, and DLco equal or higher than 35%.
In total, 596 patients who completed the CAPACITY trials were included in this analysis: 187 patients were considered to have advanced disease, whereas 409 were at a less advanced disease stage.
Out of the 187 patients with advanced disease, 100 patients were treated with Esbriet in the previous CAPACITY trial, and 87 patients with a placebo. For those with less advanced disease, 225 received Esbriet and 184 got the placebo.
During 180 weeks of follow-up, the mean duration of Esbriet exposure was 102.3 weeks for the more advanced stage, and 138.1 weeks for the less advanced disease group.
Researchers evaluated Esbriet’s efficacy by calculating the annual decline rate of predicted FVC: patients in the advanced group previously treated with Esbriet had a FVC decline of 3.8% and those who received a placebo had a FVC decline of 3.4%. Similar values were found in the less advanced stage group, with a 3.9% decline in FVC for both patient groups.
In terms of safety, nearly all patients in both groups suffered at least one side effect during treatment. Side effects included respiratory issues — cough, dyspnea (shortness of breath), respiratory tract infections, and bronchitis — as well as nausea, diarrhea, dizziness, and headaches.
Side effects due to IPF progression were higher in patients with advanced disease (56.1% for dyspnea; 58.3% for IPF worsening) compared with patients with less advanced disease (39.6% for dyspnea; 27.4% for IPF worsening). Discontinuation rates were also higher for the advanced stage group (71.7%) than in those with less advanced disease (43.3%).
Overall, “longer-term pirfenidone (Esbriet) treatment resulted in a similar rate of lung function decline and safety profile in patients with more advanced versus less advanced IPF,” the researchers wrote.
“These data suggest that pirfenidone is efficacious, well tolerated, and a feasible treatment option in patients with more advanced IPF,” the team concluded.