IN a Phase III clinical trial, nerandomilast, an oral phosphodiesterase 4B inhibitor, was associated with a smaller decline in lung function over 52 weeks in patients with progressive pulmonary fibrosis, when compared with placebo. The findings provide data on nerandomilast’s performance in a broader population beyond idiopathic pulmonary fibrosis, where it had previously been studied.
The randomized, double-blind study enrolled 1176 patients who received either nerandomilast 18 mg twice daily, nerandomilast 9 mg twice daily, or placebo. Participants were stratified based on background use of nintedanib and fibrotic pattern on high-resolution computed tomography. The primary endpoint was the absolute change from baseline in forced vital capacity (FVC) at 52 weeks.
Results showed an adjusted mean change in FVC of −98.6 ml in the 18 mg group, −84.6 ml in the 9 mg group, and −165.8 ml in the placebo group. Compared with placebo, the adjusted difference in FVC was 67.2 ml for the 18 mg group (95% CI, 31.9 to 102.5; P<0.001) and 81.1 ml for the 9 mg group (95% CI, 46.0 to 116.3; P<0.001). Background use of nintedanib was reported in 43.5% of patients. Diarrhea was the most common adverse event, occurring in 36.6% of the 18 mg group, 29.5% of the 9 mg group, and 24.7% of the placebo group. Serious adverse events occurred at similar rates across all groups. The authors conclude that nerandomilast was associated with a smaller reduction in FVC compared to placebo over 52 weeks, though long-term clinical outcomes and broader applicability require further evaluation. Reference: Maher TM et al. Nerandomilast in Patients with Progressive Pulmonary Fibrosis. N Engl J Med. 2025. doi:10.1056/NEJMoa2503643
