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 twice daily and 18 mg twice daily (hereafter nerandomilast 9 mg and 18 mg, respectively) reduced the decline in forced vital capacity at week 52 compared with placebo (primary end-point). We assessed the effects of nerandomilast up to the final database lock. Methods Time to first acute exacerbation of interstitial lung disease, hospitalisation for respiratory cause or death (key secondary end-point) and other time-to-event end-points were assessed. Results 1176 patients, of whom 512 were taking background nintedanib, received nerandomilast or placebo. At the final database lock, the mean± sd exposure to trial medication was 15.1±5.7 months and the mean± sd observation period was 17.0±4.1 months. Compared with placebo, the hazard ratio for the key secondary end-point was 0.78 (95% CI 0.61–1.00) for nerandomilast 9 mg and 0.77 (95% CI 0.60–0.99) for nerandomilast 18 mg; hazard ratios were lower among patients not taking nintedanib (0.69 (95% CI 0.49–0.97) and 0.65 (95% CI 0.46–0.92), respectively) than among those taking background nintedanib (0.90 (95% CI 0.63–1.30) and 0.93 (95% CI 0.65–1.34), respectively). For death, the hazard ratio versus placebo was 0.51 (95% CI 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 and nerandomilast 18 mg 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.