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Introduction Elafibranor (ELA) led to significant biochemical improvements in patients with PBC in the phase III ELATIVE® trial ( NCT04526665); its long-term effects on liver fibrosis are still being evaluated.1 N-terminal type III collagen propeptide (PRO-C3) is a fibrogenic activity marker, supplementing other non-invasive tests (NITs) for fibrosis, including enhanced liver fibrosis (ELF) and liver stiffness measurement (LSM).2 We report data exploring changes in PRO-C3 levels with elafibranor treatment in patients with PBC.Methods Patients completing the ELATIVE® double-blind period (DBP) were eligible to enter the open label extension (OLE) and receive daily ELA 80mg. Baseline (BL) values for this analysis were set as the last value before the first ELA dose, whether that was at the start of randomization or start of OLE. Changes over time in PRO-C3, ELF, and ELF components (HA, PIINP, and TIMP-1) were assessed. Correlations between the NITs (PRO-C3, ELF, and LSM), and between NITs and alkaline phosphatase (ALP) and total bilirubin (TB) at BL were performed.Results At data cutoff (June 2024), 153 patients had received ELA; 108 started ELA in the DBP and were followed for 156 weeks (continuous ELA), and 52 patients received placebo (PBO) for 52 weeks, 45 of whom switched to ELA in the OLE for 78 weeks (crossover ELA). Mean PRO-C3 values at DBP BL for the ELA and PBO groups, and OLE BL for the crossover ELA group were 51.4µg/L, 46.7µg/L, and 48.5µg/L, respectively. There was a trend for decline in PRO-C3 among patients who received ELA in the DBP at Week (W) 52 (mean -3.9; n=93), while values increased overall in those on PBO (+2.8; n=45). Patients on continuous ELA had stable values, maintained or decreased to W156 (-9.9; n=13). In those who switched to ELA in the OLE, there was a decrease from BL of similar magnitude to that in patients on ELA during the DBP (mean [standard error]: continuous ELA -3.9 [1.3] µg/L at W52 vs crossover ELA -5.4 [1.8] µg/L at W104). Similar changes were observed in ELF scores. 2 In analyses of the ELF score components, no clear trends or separation from PBO were observed. There was a moderate correlation between PRO-C3 and ELF (0.69) and LSM (0.59). There were weak-to-moderate correlations between TB and ELF (0.28), PRO-C3 (0.31), and LSM (0.38), and between ALP and ELF (0.37), PRO-C3 (0.35), and LSM (0.30).Conclusion(s) Long-term PRO-C3 data from ELATIVE® support previous findings that ELA stabilizes NITs for fibrosis in patients with PBC; the relationship between NITs and clinical outcomes will be assessed with continued data from the ongoing OLE. PRO-C3 correlates well with established NITs in PBC, therefore serving as a potentially useful marker of disease progression.References Kowdley KV, et al. N Eng J Med. 2024;390:795–805.Kowdley, KV, et al. Hepatology. 2025;81:60.