Late-Breaking Data Suggest Nerandomilast Beneficial for Patients with IPF and PPF

In new phase 3 findings from the FIBRONEER-IPF and FIBRONEER-ILD studies, nerandomilast met its primary endpoint in both studies evaluating responses in patients with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF).1

These late-breaking data, announced at the American Thoracic Society (ATS) International Conference in San Francisco, were detailed in a release by Boehringer Ingelheim that highlights the phase 3 findings on nerandomilast, an investigational oral, preferential inhibitor of phosphodiesterase 4B (PDE4B).1

The phase 3 FIBRONEER-IPF trial (NCT05321069) and the FIBRONEER-ILD trials (NCT05321082) were both randomized, double-blind, placebo-controlled analyses that investigators conducted to determine the efficacy and safety of nerandomilast over a minimum of 52 weeks among individuals living with IPF and PPF, respectively.1

In both studies—authored by such investigators as Toby Maher, MD, PhD, professor of Clinical Medicine at USC’s Keck School of Medicine—nerandomilast demonstrated statistically significant benefits among those treated on the 9 mg and 18 mg doses by achieving the primary study’sendpoint: a reduction in the absolute decline in forced vital capacity (FVC) [mL] from the point of baseline through the 52-week mark compared to placebo. FVC is a key indicator of pulmonary function.

Maher and colleagues further concluded that rates of drug discontinuation resulting from adverse events were comparable between treatment and placebo cohorts in both of the studies. In FIBRONEER-IPF, the drug was permanently discontinued due to adverse events among only 14.0% of those on 18 mg of nerandomilast, 11.7% of those on 9 mg, and 10.7% of those in the placebo arm.

In the FIBRONEER-ILD study, discontinuation of the medication took place in 10.0% of trial subjects on the 18 mg dose of the drug, 8.1% on 9 mg, and 10.2% of those in the placebo arm. Notably, Maher et al found no differences between the nerandomilast and placebo groups in the incidence of key adverse events of special interest, including depression, vasculitis, suicidal ideation, or drug-induced liver injury.

In both analyses, their key secondary composite endpoint—which included time to the first hospitalization due to a respiratory cause, first acute exacerbation of IPF or ILD, or death—was not attained. However, within the FIBRONEER-ILD trial, a numerically lower percentage of patients receiving nerandomilast experienced death compared to those in the placebo group.

"After several challenges in the scientific community to bring forward new clinical data, IPF and PPF continue to take a devastating toll on patients,” Maher said in a statement.1 “Having two phase III trials meet the primary endpoint is a major breakthrough for the scientific community, highlighting nerandomilast’s potential to have a meaningful impact on patients’ unmet needs, being studied as mono therapy or in combination with current treatments.”

Nerandomilast remains an investigational drug. It has not yet been given regulatory approval, as its safety and efficacy have not been confirmed.

References

1. Global phase III trials demonstrate that nerandomilast slowed lung function decline in IPF and PPF, with similar discontinuation rates to placebo. Boehringer Ingelheim. May 19, 2025. Accessed May 19, 2025. https://www.boehringer-ingelheim.com/human-health/lung-diseases/pulmonary-fibrosis/phase-3-trials-nerandomilast-slowed-lung-function-decline-ipf-and-ppf.