Nerandomilast in progressive pulmonary fibrosis: data from the whole follow-up period of the FIBRONEER-ILD trial

Background In the FIBRONEER-ILD trial in patients with progressive pulmonary fibrosis (PPF), nerandomilast 9 mg bid and 18 mg bid reduced the decline in forced vital capacity at week 52 compared with placebo (the primary endpoint). We assessed the effects of nerandomilast up to the final database lock. Methods Time to first acute exacerbation of ILD, hospitalisation for respiratory cause, or death (key secondary endpoint) and other time-to-event endpoints were assessed. Results 1176 patients, of whom 512 were taking background nintedanib, received nerandomilast or placebo. At final database lock, mean ( sd ) exposure to trial medication was 15.1 (5.7) months and mean ( sd ) observation period was 17.0 (4.1) months. Compared with placebo, the hazard ratio (95% CI) for the key secondary endpoint was 0.78 (0.61, 1.00) for nerandomilast 9 mg bid and 0.77 (0.60, 0.99) for nerandomilast 18 mg bid; hazard ratios were lower among patients not taking nintedanib (0.69 0.49, 0.97 and 0.65 0.46, 0.92, respectively) than among those taking background nintedanib (0.90 0.63, 1.30 and 0.93 0.65, 1.34, respectively). For death, the hazard ratio (95% CI) versus placebo was 0.51 (0.34, 0.78) for both nerandomilast doses. Adverse events led to discontinuation of trial medication in 12.5%, 12.0% and 12.3% of the placebo, nerandomilast 9 mg bid and nerandomilast 18 mg bid groups, respectively. Conclusions In the FIBRONEER-ILD trial in patients with PPF, nerandomilast reduced the risk of clinically important outcomes, including death, over the whole trial. Nerandomilast had a favourable safety and tolerability profile.