C103-03 Effect of Nerandomilast on Risk of Death in Patients With Idiopathic Pulmonary Fibrosis (IPF) and Progressive Pulmonary Fibrosis (PPF)

Abstract Rationale 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 decline in forced vital capacity (FVC) at week 52 versus placebo (primary endpoint). We assessed the effect of nerandomilast on time to death. Methods Data from FIBRONEER-IPF and FIBRONEER-ILD were pooled. The primary analysis of time to death was based on deaths (except deaths after lung transplant) that occurred until the final database lock, which took place after all patients had completed an end-of-treatment visit. We assessed time to death based on events that occurred while patients were on-treatment plus 7, 30, 60, or 90 days afterwards, time to death or lung transplant, and time to respiratory-related death. We performed a tipping point analysis to assess how large deviations from the assumption that missing data were missing at random would need to be to lose statistical significance. Results Among 2353 patients, mean exposure to trial medication was 15.0 months and mean observation period was 16.7 months. Overall, 2250 (95.6%) patients completed the planned observation period and had confirmed vital status. Compared with placebo, the hazard ratio for death was 0.67 (95% CI: 0.49, 0.90) for nerandomilast 9 mg bid and 0.57 (95% CI: 0.41, 0.78) for nerandomilast 18 mg bid. The risks of death while on-treatment and the risk of death or lung transplant were lower with nerandomilast versus placebo (Figure). Respiratory-related death occurred in 9.0%, 5.5% and 4.6% of patients in the placebo, nerandomilast 9 mg bid and nerandomilast 18 mg bid groups, respectively, giving hazard ratios of 0.59 (95% CI: 0.40, 0.86) for nerandomilast 9 mg bid and 0.51 (95% CI: 0.34, 0.77) for nerandomilast 18 mg bid. The tipping point analysis showed that the effect of nerandomilast versus placebo on time to death would only lose statistical significance in extreme scenarios such as if 0 of the 26 patients with missing data in the placebo group, 9 of the 36 patients with missing data in the nerandomilast 9 mg bid group and 20 of the 41 patients with missing data in the nerandomilast 18 mg bid group died on the day of discontinuation. Conclusions Based on pooled data from the FIBRONEER trials, nerandomilast was associated with a reduced risk of death. Analyses of on-treatment data, the potential impact of missing data and respiratory-related deaths supported the robustness of this finding. This abstract is funded by: The FIBRONEER-IPF and FIBRONEER-ILD trials were supported by Boehringer Ingelheim.