Nerandomilast Shown Safe, Effective in IPF Among US FIBRONEER-IPF Subgroup

US-based patients with idiopathic pulmonary fibrosis (IPF) had a slower decline in forced vital capacity (FVC) when they received nerandomilast (Jascayd; Boehringer Ingelheim) compared with placebo, a new subgroup analysis of the FIBRONEER-IPF trial showed.¹

The therapy also had an acceptable safety profile and tolerability, the investigators found. The findings were reported at the American College of Chest Physicians Annual Meeting, held October 19-22, in Chicago.

Nerandomilast is an orally administered preferential inhibitor of phosphodiesterase 4B that has been shown to have both antifibrotic and immunomodulatory effects. FIBRONEER-IPF was a major, 36-country, double-blind, placebo-controlled trial in which patients with IPF were randomized on a 1:1:1 basis to receive nerandomilast at a dose of 18 mg twice daily, a dose of 9 mg twice daily, or placebo. Most of the patients (77.7%) were taking nintedanib (Ofev; Boehringer Ingelheim) or pirfenidone (Esbriet; Genentech) at enrollment.²

The trial found that nerandomilast slowed the rate of FVC decline in both dosage cohorts compared to placebo, and that the most common adverse event in the nerandomilast groups was diarrhea.

In the new subgroup analysis, researchers looked specifically at how the therapy performed among patients in the US. Of the 1177 participants in the original trial, 196 were from the US. Among those patients, 70 received placebo, 70 were in the nerandomilast 9 mg twice-daily group, and 56 were in the 18 mg twice-daily group.

The US patients had a mean age of 73.1 years, and 81.6% were male. The baseline FVC was 76.5% predicted, and the diffusing capacity of the lung for carbon monoxide (DLco) was 50.9% predicted. Among the US patients, 53.6% took nintedanib and 30.1% took pirfenidone, the authors said.

After a year, the adjusted mean changes in FVC (mL) were 257.9 (standard error [SE], 33.6) in the placebo group, 152.7 (SE, 32.9) in the nerandomilast 9 mg group (difference vs placebo, 105.2 [95% CI, 13.0-197.4]), and 126.2 (SE, 36.9) in the nerandomilast 18 mg group (difference vs placebo, 131.7 [95% CI, 33.8-229.6]).

At the first database lock, 30% of US participants in the placebo group had experienced the composite endpoint of acute exacerbation, hospitalization for a respiratory cause, or death. That compared to 21.4% in the 9 mg group (HR vs placebo, 0.86 [95% CI, 0.44-1.69]), and 19.6% in the 18 mg group (HR vs placebo, 0.74 [95% CI, 0.36-1.54]). The median time of exposure to the therapy at the first database lock was 13.2 months, the authors said.

As in the broader trial population, diarrhea was the most commonly reported adverse event, with rates of 14.3%, 34.3%, and 42.9% in the placebo, 9 mg, and 18 mg groups, respectively. Yet, patients in the placebo group were most likely to discontinue due to adverse events (15.7%), compared with 12.9% in the 9 mg group and 10.7% in the 18 mg group.

The authors said their subgroup analysis aligned with the broader FIBRONEER-IPF trial.

“Among US patients receiving standard of care therapy for IPF, the addition of nerandomilast slows disease progression,” they concluded.

References

1. Oldham JM, Maher TM, Liu Y, et al. Effect of nerandomilast in US patients with idiopathic pulmonary fibrosis: subgroup analysis of the FIBRONEER-IPF Trial. Presented at: CHEST 2025 Annual Meeting; October 19-22, 2025; Chicago, IL.

2. Richeldi L, Azuma A, Cottin V, et al. Nerandomilast in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2025;392(22):2193-2202. doi:10.1056/NEJMoa2414108