Interstitial lung disease · Antifibrotics in IPF
Nerandomilast in Patients with Idiopathic Pulmonary Fibrosis
| Design | Phase 3, double-blind, placebo-controlled RCT with two doses |
|---|---|
| Treatment | Nerandomilast 18 mg or 9 mg twice daily, on top of background antifibrotic therapy |
| Control | Placebo |
| Population | 1177 patients with idiopathic pulmonary fibrosis, 77.7% already taking nintedanib or pirfenidone |
| Follow-up | 52 weeks |
| Primary endpoint | Absolute change from baseline in FVC at week 52 |
| Result | FVC change -114.7 mL (95% CI -141.8 to -87.5) with nerandomilast 18 mg, -138.6 mL (-165.6 to -111.6) with 9 mg, and -183.5 mL (-210.9 to -156.1) with placebo. Adjusted difference versus placebo 68.8 mL (30.3 to 107.4, p<0.001) for 18 mg and 44.9 mL (6.4 to 83.3, p=0.02) for 9 mg. Diarrhoea was the most frequent adverse event. |
| Secondary endpoints | Time to first acute exacerbation, hospitalisation, death |
In patients with idiopathic pulmonary fibrosis, treatment with nerandomilast resulted in a smaller decline in the FVC than placebo over a period of 52 weeks.
The trial authors, in the published abstract
The important design feature is that three quarters of participants stayed on pirfenidone or nintedanib, so the effect is additive rather than a replacement. That is the first time an IPF drug has been shown to add to what patients are already taking.
Richeldi L, Azuma A, Cottin V, et al. Nerandomilast in Patients with Idiopathic Pulmonary Fibrosis. N Engl J Med 2025 Jun 12;392(22):2193-2202.