Introduction: 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 slowed disease progression, with a significant reduction in decline in FVC (mL) at week 52 versus placebo (the primary endpoint).
Objectives: To assess the effect of nerandomilast in subgroups by FVC % predicted at baseline in these trials.
Materials and Methods: The FIBRONEER-IPF and FIBRONEER-ILD trials enrolled patients with FVC ≥45% predicted. In a post-hoc analysis, we assessed the change from baseline in FVC (mL) at week 52 across subgroups by categories of FVC % predicted at baseline. Treatment-by-subgroup interaction p-values were calculated to assess potential heterogeneity in the effect of nerandomilast versus placebo across the subgroups in each trial.
Results: Overall, 1177 and 1176 patients received trial medication in FIBRONEER-IPF and FIBRONEER-ILD, respectively. At baseline of FIBRONEER-IPF, 52 patients (4.4%) had FVC ≤50% predicted, 336 (28.5%) had FVC >50%–≤70% predicted, 505 (42.9%) had FVC >70%–≤90% predicted, and 284 (24.1%) had FVC >90% predicted. At baseline of FIBRONEER-ILD, 121 patients (10.3%) had FVC ≤50% predicted, 489 (41.6%) had FVC >50%–≤70% predicted, 442 (37.6%) had FVC >70%–≤90% predicted, and 124 (10.5%) had FVC >90% predicted. There was no evidence of heterogeneity in the effect of nerandomilast versus placebo on change from baseline in FVC (mL) at week 52 in subgroups by FVC % predicted at baseline in FIBRONEER-IPF (interaction p=0.88 for nerandomilast 9 mg bid, p=0.75 for nerandomilast 18 mg bid) or FIBRONEER-ILD (interaction p=0.93 for nerandomilast 9 mg bid, p=0.76 for nerandomilast 18 mg bid) (Figure).
Conclusions: In patients with IPF and PPF, the effect of nerandomilast on slowing disease progression was consistent irrespective of baseline FVC % predicted, including in patients with well-preserved FVC (>90% predicted).