FIBRONEER-ILD: Novel PDE4B Inhibitor Slows FVC Decline in Progressive Pulmonary Fibrosis

Nerandomilast significantly slowed lung function decline in patients with progressive pulmonary fibrosis (PPF), according to results from the phase 3 FIBRONEER-ILD trial.¹

In the 52-week, double-blind study, patients who received nerandomilast had a significantly smaller drop in forced vital capacity (FVC) compared with placebo, whether or not they were taking background nintedanib. Patients taking nerandomilast 18 mg or 9 mg twice daily saw adjusted mean FVC declines of 98.6 mL and 84.6 mL, respectively, compared with 165.8 mL in the placebo group. These differences were statistically significant at 67.2 mL and 81.1 mL, respectively (P < .001). The findings were published in The New England Journal of Medicine and presented the American Thoracic Society (ATS) 2025 International Conference alongside the FIBRONEER-IPF study.²

The trial enrolled 1176 patients across 44 countries with fibrosing ILDs other than idiopathic pulmonary fibrosis (IPF), such as autoimmune ILDs, hypersensitivity pneumonitis, and unclassifiable fibrosing ILDs.¹ Notably, 43.5% were on background nintedanib therapy, the only approved treatment for PPF to date. Efficacy was consistent regardless of background therapy.

Patients taking nerandomilast, an oral phosphodiesterase 4B (PDE4B) inhibitor, also experienced numerically fewer acute exacerbations, respiratory-related hospitalizations, or deaths compared with those taking placebo. While this composite key secondary end point did not reach statistical significance, the association was stronger in the 18-mg group (HR, 0.77; 95% CI, 0.59-1.01; P = .06) than the 9-mg group (HR, 0.88; 95% CI, 0.68-1.14; P = .34).

However, mortality alone was significantly lower in both nerandomilast groups compared with placebo, occurring in:

• 6.1% of patients on nerandomilast 18 mg (HR, 0.48; 95% CI, 0.30-0.79)
• 8.4% of patients on nerandomilast 9 mg (HR, 0.60; 95% CI, 0.38-0.95)
• 12.8% of patients on placebo

Adverse events were common but mostly mild to moderate; rates of serious adverse events and treatment discontinuations were similar across all groups. Diarrhea was the most frequently reported issue, occurring in 36.6% of the 18-mg group, 29.5% of the 9-mg group, and 24.7% of the placebo group, but less than 2% of patients discontinued the PDE4B inhibitor for this reason.

Importantly, patient-reported outcomes such as dyspnea, cough, and fatigue scores on the Living with Pulmonary Fibrosis questionnaire did not differ significantly between groups after 1 year of treatment.

The FIBRONEER-ILD results build on findings from the FIBRONEER-IPF trial, which showed similar benefits of nerandomilast in patients with IPF, a distinct yet related fibrosing ILD population.² Together, researchers say the trials support the potential role of nerandomilast as a new oral option for patients across a broader spectrum of progressive fibrotic lung diseases.

“In contrast to the current drugs, which can't be used in combination because of difficulty with tolerability, nerandomilast can be used in combination with existing antifibrotic drugs,” Toby Maher, MD, PhD, professor of clinical medicine, Keck School of Medicine at USC, told The American Journal of Managed Care^® (AJMC^®) in an exclusive interview at ATS 2025.³ “Certainly, looking at the data and from my experience of being involved in the trial, it looks like nerandomilast is much better tolerated than either of the 2 existing therapies, so it's a very exciting option for patients in the future.”

References

1. Maher TM, Assassi S, Azuma A, et al. Nerandomilast in patients with progressive pulmonary fibrosis. N Engl J Med. Published online May 19, 2025. doi:10.1056/NEJMoa2503643

2. Klein HE. Nerandomilast slows lung function decline in patients with IPF. AJMC. May 19, 2025. Accessed May 20, 2025. https://www.ajmc.com/view/nerandomilast-slows-lung-function-decline-in-patients-with-ipf

3. Steinzor P, Maher T. FIBRONEER trials show nerdanomilast's promise as new treatment option for IPF/PPF: Toby Maher, MD, PhD. AJMC. May 20, 2025. Accessed May 20, 2025. https://www.ajmc.com/view/fibroneer-trials-show-nerdanomilast-s-promise-as-new-treatment-option-for-ipf-ppf-toby-maher-md-phd