C103-14 Predicting Long-Term Survival Benefit of Nerandomilast in Patients With Idiopathic Pulmonary Fibrosis

Abstract Rationale In the FIBRONEER-IPF trial, nerandomilast 9 mg bid and 18 mg bid slowed progression of IPF compared with placebo. At the end of the trial (median observation time: 17 months), nerandomilast 9 mg bid and 18 mg bid had a numerical benefit on the risk of death versus placebo when used as monotherapy (HR 0.56 95% CI: 0.21, 1.49 and 0.26 95% CI: 0.07, 0.91, respectively). When used with background nintedanib, nerandomilast 18 mg bid also had a numerical benefit on survival (HR 0.64 95% CI: 0.30, 1.37). We used a parametric survival model to estimate the effect of nerandomilast on long-term survival. Methods Seven parametric models were fit to survival data from patients not taking background antifibrotic therapy (nintedanib or pirfenidone) and from patients taking background nintedanib in the FIBRONEER-IPF trial. The Weibull distribution was selected as the most appropriate model based on model fit statistics (AIC & BIC) and clinical plausibility. Survival data over 30 years were modelled. The analysis assumed that the effect of nerandomilast on survival would remain consistent and did not account for treatment discontinuations. The US general population was used as a reference population. Results In patients not taking background antifibrotic therapy, median (Q1, Q3) survival was estimated as 3.7 (2.4, 5.3) years for placebo, 5.8 (3.2, 9.8) years for nerandomilast 9 mg bid and 9.1 (4.0, 19.5) years for nerandomilast 18 mg bid. In patients taking background nintedanib, median (Q1, Q3) survival was estimated as 4.6 (2.9, 6.5) years for placebo, 5.1 (3.3, 7.8) years for nerandomilast 9 mg bid and 6.0 (3.5, 9.5) years for nerandomilast 18 mg bid. Estimated survival curves are shown in the Figure. Conclusions A model that extrapolated survival data from the FIBRONEER-IPF trial suggests a 2.5-fold increase in median survival with nerandomilast 18 mg bid monotherapy compared with no therapy and a 1.3-fold increase in median survival with nerandomilast 18 mg bid in combination with nintedanib compared to nintedanib alone. Further evidence on the long-term effect of nerandomilast on survival may come from the open-label extension trial (FIBRONEER-ON) and real-world studies. This abstract is funded by: The FIBRONEER-IPF trial was supported by Boehringer Ingelheim.