BI 1015550 Effective in Prevention of Decreased Lung Function in IPF Patients

Luca Richeldi, MD, PhD

New data suggests that the treatment of idiopathic pulmonary fibrosis (IPF) with BI 1015550- an oral preferential inhibitor of the phosphodiesterase 4 (PDE4) subtype- either alone or with an antifibrotic agent prevented a decrease in lung function.

The phase 2 data was published today in the New England Journal of Medicine to coincide with the American Thoracic Society 2020 International Conference taking place in San Francisco from May 13-18.

Currently, only 2 approved antifibrotic drugs- nintedanib and pirfenidone- are available to slow the progression of fibrosis in patients with IPF. This suggests that additional treatments could be used either with or instead of existing antifibrotic therapies.

Furthermore, PDE4 inhibition has been associated with positive anti-inflammatory and antifibrotic effects that researchers have deemed beneficial to patients with IPF.

An investigative team led by Luca Richeldi, MD, PhD, of the Catholic University of Sacred Heart, sought to determine the efficacy and safety of BI 1015550 in patients with IPF.

This multicenter, randomized, double-blind, phase 2 trial enrolled patients 40 years or older with a previous diagnosis of IPF, with patients with a usual interstitial pneumonia or a pattern of probable usual interstitial pneumonia on high-resolution computed tomography of the chest being deemed eligible for inclusion.

Patients with a forced vital capacity (FVC) were of at least 45% of the predicted value and a diffusing capacity of the lungs between 25% and less than 80% of the predicted value.

Those included in the study were permitted to continue the use of nintedanib or pirfenidone if they had been receiving a stable dose for at least 8 weeks leading up to screening.

The study utilized a total of 90 sites from 22 countries, of which eligible participants were selected and randomly assigned 2:1 to receive BI 1015550 at a dose of 18 mg twice daily or a matching oral placebo for 12 weeks.

Overall, 150 patients were deemed eligible for inclusion, with 147 undergoing randomization.At least 60 patients being randomly assigned to each group. The first patient underwent screening on August 12, 2020, and the last patient completed the trial on October 15, 2021.

The median change of FVC- the primary endpoint- among patients without background antifibrotic use was 5.7 ml (95% credible interval, –39.1 to 50.5) in the BI 1015550 group compared to –81.7 ml (95% credible interval, –133.5 to –44.8) in the placebo group.

Regarding patients with background antifibrotic use, median FVC was 2.7 ml (95% credible interval, –32.8 to 38.2) in the BI 1015550 group and –59.2 ml (95% credible interval, –111.8 to –17.9) in the placebo group.

Despite the relatively short nature of this trial, investigators felt it showed the stabilization of FVC with BI 1015550 therapy and provided a proof of concept for longer phase 3 trials. They added that a phase 3 trial would be necessary in evaluating these preliminary findings.

“The safety profile of BI 1015550, in combination with the observed effects on the FVC, warrants further research as a treatment for IPF and other forms of progressive pulmonary fibrosis,” the investigators wrote.