Nerandomilast in Patients with Idiopathic Pulmonary Fibrosis.

Summary

In a 52-week, double-blind phase 3 trial (n=1,177), nerandomilast attenuated FVC decline in IPF versus placebo, including in patients already receiving nintedanib or pirfenidone. Diarrhea was the most frequent adverse event; serious adverse events were balanced.

Key Findings

• Adjusted mean FVC change at week 52: −114.7 mL (18 mg), −138.6 mL (9 mg), −183.5 mL (placebo).
• Adjusted differences vs placebo: +68.8 mL (18 mg; 95% CI 30.3–107.4; P<0.001) and +44.9 mL (9 mg; 95% CI 6.4–83.3; P=0.02).
• 77.7% were on nintedanib or pirfenidone at enrollment; benefit observed across background therapy strata.
• Diarrhea occurred in 41.3% (18 mg), 31.1% (9 mg), 16.0% (placebo); serious adverse events were similar across groups.

Clinical Implications

Nerandomilast could be considered as an add-on or alternative antifibrotic option to slow lung function decline in IPF; monitoring for gastrointestinal adverse effects is required.

Limitations

• Primary endpoint was FVC change; effects on mortality or acute exacerbations were not established.
• Gastrointestinal side effects (notably diarrhea) were more frequent with nerandomilast.

Future Directions

Evaluate long-term outcomes (mortality, exacerbations), head-to-head comparisons with existing antifibrotics, and biomarker-driven responder analyses.