Boehringer Ingelheim has presented new findings from its Phase III FIBRONEER program showing that nerandomilast may reduce the risk of death in patients with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF).

The pooled data were shared at the European Respiratory Society (ERS) International Congress 2025 in Amsterdam, which took place from 27 September to 1 October.

Nerandomilast is a selective inhibitor targeting phosphodiesterase 4B (PDE4B) and is currently under regulatory review. The US Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for IPF in 2022 and extended it to PPF in April 2025. An FDA decision on the New Drug Application for IPF is anticipated in the fourth quarter of 2025, with a separate application for PPF already submitted. Reviews are also ongoing in the European Union (EU), the UK, and China.

Phase III data

The analysis combined results from two global Phase III studies, FIBRONEER-IPF (NCT05321069) and FIBRONEER-ILD (NCT05321082), that evaluated nerandomilast with and without background antifibrotic treatment.

Both studies had previously met their primary endpoint, demonstrating that the drug slowed lung function decline as measured by forced vital capacity (FVC). However, they did not meet the key secondary endpoint of reducing acute exacerbations, hospitalizations, or death during the trial period.

When pooled, the data suggested a nominally significant reduction in mortality risk. Patients receiving the higher 18mg dose of nerandomilast showed a 43% reduction in the risk of death compared to placebo. Among those treated with nerandomilast without background therapy, the effect was even more pronounced, with a 59% reduction in mortality risk. A similar downward trend was also observed in patients taking background nintedanib, where the reduction reached 41%.

“Mortality remains unacceptably high in pulmonary fibrosis, with half of patients dying within five years of diagnosis,” said Shashank Deshpande, Chairman of the Board of Managing Directors and Head of Human Pharma at Boehringer Ingelheim. “These results represent the first Phase III trial program to demonstrate a nominally significant reduction in the risk of death in progressive pulmonary fibrosis.”

Nominal significance indicates a clear trend toward benefit, though the results fall short of the statistical rigor required to confirm a definitive survival advantage.

Dr. Marlies Wijsenbeek of Erasmus MC University Medical Centre, who presented the results, said the data highlight nerandomilast’s potential, particularly as a monotherapy. “The new pooled data zoom in on nerandomilast’s potential as monotherapy, pairing efficacy with a nominally significant reduction in the risk of death,” she said. “While exploratory, they add to the growing body of evidence and may impact future research directions in pulmonary fibrosis.”

Safety Profile and Tolerability

Across both trials, nerandomilast demonstrated a safety profile consistent with prior studies. Discontinuation rates due to adverse events were similar between the nerandomilast and placebo arms. The most frequent side effect was diarrhea, reported in up to 27.4% of patients taking the higher 18mg dose without background therapy, compared to 14.6% in the placebo group. Rates were higher among patients receiving background antifibrotic treatment. Serious adverse events occurred in 39% and 40.5% of patients in the 9mg and 18mg nerandomilast groups, respectively, versus 44.7% in the placebo arm.

Importantly, tolerability has been a limiting factor for many existing pulmonary fibrosis therapies. A favorable safety profile could prove pivotal in long-term disease management, where adherence remains a challenge.

Other late-stage therapy in IPF is Celea Therapeutics’ deupirfenidone, for which Phase III trials are currently planned. The trial met its primary endpoint using a prespecified Bayesian analysis, showing a 98.5% probability that pooled deupirfenidone arms were superior to placebo in slowing FVC decline.

In early development, Cereno Scientific’s CS014, a novel HDAC inhibitor, cleared Phase I with clean safety/tolerability and pharmacokinetics reaching exposures predicted to impact fibrosis biology, paving the way for a Phase II start in the first half of 2026.