Among patients in the United States who receive standard-of-care therapy for idiopathic pulmonary fibrosis, adding nerandomilast slows disease progression. In the US subgroup of the FIBRONEER-IPF trial, nerandomilast demonstrated clinically relevant benefits in preserving lung function, with acceptable safety and tolerability.
Nerandomilast is a preferential phosphodiesterase 4B inhibitor with antifibrotic and immunomodulatory effects. In the Phase 3 FIBRONEER-IPF trial in patients with IPF, nerandomilast 9 mg twice daily and 18 mg twice daily reduced FVC decline over 52 weeks compared to placebo, with acceptable safety and tolerability.
The researchers analyzed the outcomes of 70 US patients randomized to receive placebo, 70 patients who received nerandomilast 9 mg twice daily, and 56 who received nerandomilast 18 mg twice daily, stratified using nintedanib/pirfenidone versus neither. The primary measure was the change in FVC from baseline at week 52, time to first acute exacerbation, hospitalization for respiratory illness, or death, up to the first database lock, which occurred after the last patient had completed the week 52 visit.
The mean participant age at baseline was 73.1 years, and 81.6% were male. Forced vital capacity (FVC) was 76.5% predicted, and diffusing capacity of the lungs for carbon monoxide (DLCO) was 50.9% predicted. Overall, 53.6% of patients took nintedanib and 30.1% took pirfenidone.
Nerandomilast Slowed FVC Decline Compared to Placebo
Adjusted mean changes in FVC at week 52 showed declines of 257.9 mL in the placebo group, 152.7 mL in the nerandomilast 9 mg twice daily group, and 126.2 mL in the nerandomilast 18 mg twice daily group. The difference versus placebo was 105.2 mL for the 9 mg dose and 131.7 mL for the 18 mg dose.
The mean exposure to trial medication until the first database lock was 13.2 months. Up to that time, the composite endpoint of acute exacerbation, hospitalization for respiratory illness, or death involved 30.0% of the placebo group, 21.4% of the nerandomilast 9 mg group (HR vs placebo, 0.86), and 19.6% of the nerandomilast 18 mg group (HR vs placebo, 0.74).
The composite endpoint of acute exacerbation, hospitalization for respiratory cause, or death was experienced by 30.0% of the placebo group, 21.4% of the nerandomilast 9 mg twice daily group, and 19.6% of the nerandomilast 18 mg twice daily group.
Over 52 weeks, the most frequent adverse event was diarrhea, reported in 14.3%, 34.3%, and 42.9% of patients in the placebo, nerandomilast 9 mg, and nerandomilast 18 mg groups, respectively. Adverse events caused 15.7%, 12.9%, and 10.7% of the placebo, nerandomilast 9 mg, and nerandomilast 18 mg groups, respectively, to discontinue the medication.
Reference
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, October 19-22, 2025; Chicago.
