Abstract Rationale Nerandomilast is a preferential inhibitor of phosphodiesterase 4B that has antifibrotic and immunomodulatory effects. In the FIBRONEER-IPF trial in patients with IPF and the FIBRONEER-ILD trial in patients with PPF, nerandomilast 9 mg bid and 18 mg bid reduced the decline in FVC at week 52 versus placebo (the primary endpoint). We investigated the effect of nerandomilast in the US patients in these trials. Methods Data from the FIBRONEER-IPF and FIBRONEER-ILD trials were pooled. In the US patients, we assessed change from baseline in FVC (mL) at week 52; time to first acute exacerbation of ILD, hospitalization for respiratory cause, or death up to the end of the trial (which took place after all patients completed an end-of-treatment visit); and time to death up to the end of the trial. We assessed adverse events over 52 weeks. Analyses were descriptive. Results Of 2353 patients in the pooled population, 335 (14.2%) were from the US (120 placebo, 114 nerandomilast 9 mg bid, 101 nerandomilast 18 mg bid). Of these patients, 184 (54.9%) took nintedanib and 59 (17.6%) took pirfenidone as background therapy. In both the overall pooled population and the US patients, the decline in FVC at week 52 was smaller with both doses of nerandomilast than placebo (Figure). Mean exposure to trial medication during the trial in the US subgroup was 15.0 months. In the US patients, the composite outcome of acute exacerbation of ILD, hospitalization for respiratory cause, or death was experienced by 35.0% of the placebo group, 27.2% of the nerandomilast 9 mg bid group (HR vs placebo, 0.88 95% CI: 0.55, 1.40) and 20.8% of the nerandomilast 18 mg bid group (HR vs placebo, 0.55 95% CI: 0.32, 0.93). Death occurred in 15.8% of the placebo group, 12.3% of the nerandomilast 9 mg bid group (HR vs placebo, 0.98 95% CI: 0.49, 1.96) and 6.9% of the nerandomilast 18 mg bid group (HR vs placebo, 0.45 95% CI: 0.19, 1.07). Adverse events led to discontinuation of trial medication in 14.2% of the placebo group, 10.5% of the nerandomilast 9 mg bid group and 7.9% of the nerandomilast 18 mg bid group. Diarrhea was the most frequent adverse event. Conclusions Consistent with observations in the overall population, in the US patients in the FIBRONEER trials, nerandomilast slowed decline in FVC, reduced the risk of clinically relevant outcomes including death, and was well tolerated. This abstract is funded by: The FIBRONEER-IPF and FIBRONEER-ILD trials were supported by Boehringer Ingelheim.
Flaherty et al. (2026) studied this question.