Boehringer Ingelheim today announced new data from the global Phase III FIBRONEER™ program on nerandomilast, an investigational oral preferential PDE4B inhibitor, which is currently not approved for use. The new pooled analyses, the first to demonstrate a nominally significant reduction in risk of death across IPF and PPF, was presented in a poster at the European Respiratory Society (ERS) International Congress 2025 in Amsterdam. Nominal significance means that the trial results showed a clear trend that suggests a possible benefit; however, the evidence does not meet the strict criteria to declare it statistically significant.
Both phase III trials, FIBRONEER™-IPF and FIBRONEER™-ILD, had met their primary endpoint, demonstrating that nerandomilast slowed lung function decline in IPF and PPF, with similar discontinuation rates to placebo.2,3 Although both trials did not meet the key secondary endpoint (time to first acute IPF/ILD exacerbation, first hospitalization for respiratory cause, or death over duration of trial),2,3 the pooled analysis resulted in a nominally significant reduction in risk of death across IPF and PPF for the 18mg nerandomilast dose vs placebo in monotherapy and with background nintedanib.1 The trend was more pronounced in monotherapy.1
“The new pooled data zoom in on nerandomilast’s potential as monotherapy, pairing efficacy with a nominally significant reduction in the risk of death. While the findings are exploratory, they add to the growing body of evidence and may impact future research directions in pulmonary fibrosis,” said Marlies Wijsenbeek, Erasmus MC University Medical Centre. “The new findings go hand-in-hand with nerandomilast’s favorable safety and tolerability profile in previous studies. In a disease area with many patients discontinuing treatment,4 mostly related to limited tolerability of current therapies, this could really improve outcomes for patients.”
Findings of the pooled analysis
In both FIBRONEER™ trials, patients (FIBRONEER™-IPF, n=1177; FIBRONEER™-ILD, n=1176) were randomized to receive nerandomilast 9mg twice per day, 18mg twice per day, or placebo.2,3 The data was pooled and changes in FVC over 76 weeks and clinically relevant outcomes (acute exacerbations, respiratory hospitalization, and death) were analyzed. The analyses included the overall population and subgroups of patients by use of background therapy at baseline.1
In the overall trial population, a nominally significant reduction in the risk of death by 43% was observed in patients who received 18mg (HR 0.57 [CI: 0.41-0.78)].1 A nominally significant reduction in the risk of death, by 59%, was observed in patients who received 18mg nerandomilast without background therapy (HR 0.41 [CI: 0.24-0.70)].1 This downward trend was also seen in patients taking background nintedanib with a nominally significant reduction in the risk of death by 41% (HR 0.59 [CI: 0.37-0.94)].1
“For people living with pulmonary fibrosis, mortality remains unacceptably high, with every second person dying within 5 years of diagnosis,” said Shashank Deshpande, Chairman of the Board of Managing Directors and Head of Human Pharma at Boehringer Ingelheim. “As the first Phase III trial program to demonstrate a nominally significant reduction in the risk of death in progressive pulmonary fibrosis, FIBRONEER heralds a significant advance for this group of patients, who face a devastating diagnosis and very limited treatment options.”
In the pooled analysis, nerandomilast showed a favorable safety and tolerability profile, with a similar rate of discontinuation due to adverse events as placebo, consistent with the prior phase III results.1 The most frequent adverse event in the nerandomilast group without background therapy was diarrhea, reported in 14.6% in the placebo group, 17.5% in the nerandomilast 9 mg group, and 27.4% in the nerandomilast 18 mg group.1 Patients receiving either background nintedanib or pirfenidone reported diarrhea in 27.1% in the placebo group, in 41.9% in the 9mg nerandomilast group and in 47.7% in the 18mg nerandomilast group. In all patients, serious adverse events occurred in 44.7%, 39%, and 40.5% of patients treated with placebo, nerandomilast 9 mg, and nerandomilast 18 mg, respectively.1
These latest FIBRONEER™ findings reinforce nerandomilast’s potential as a new treatment for IPF and PPF.1
