Abstract

Background

The antifibrotics (AF) nintedanib and pirfenidone slow, but do not stop, progression of idiopathic pulmonary fibrosis (IPF).

Clinical data indicate that BI 1015550, a preferential inhibitor of PDE4B, prevents FVC decline in IPF, with or without background AF.¹ Preclinical studies show a synergistic effect on inhibiting fibroblast proliferation when BI 1015550 is given with nintedanib.²

Methods

A post hoc analysis of the Phase 2 study that evaluated the efficacy and safety of BI 1015550 in IPF.¹ The adjusted mean change from baseline in FVC at Week 12 was assessed based on baseline background AF (nintedanib/pirfenidone).

Results

Patients received BI 1015550/placebo without AF (n=48/25), with nintedanib (n=26/17) or with pirfenidone (n=23/8).

The adjusted mean change in FVC at Week 12 in the BI 1015550 arm was +6.1 mL without AF, +23.4 mL with nintedanib and –18.8 mL with pirfenidone. The change in the placebo arm was –95.6 mL without AF, –82.0 mL with nintedanib and –80.1 mL with pirfenidone (Fig).

Adverse events (AE) were common when BI 1015550 or placebo were given with nintedanib (81% & 77%) or with pirfenidone (65% & 50%), with diarrhoea the most frequent AE, regardless of background AF.

Conclusion

BI 1015550 may have more pronounced added clinical benefit when taken with nintedanib than with pirfenidone on preventing FVC decline in IPF patients.

¹Richeldi N Engl J Med 2022.doi:10.1056/NEJMoa2201737

²Herrmann Front Pharmacol 2022;13:838449