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Introduction In the double-blind period (DBP) of the phase II ELMWOOD trial ( NCT05627362), elafibranor (ELA) was well tolerated and improved cholestasis biochemical markers in patients with PSC compared with placebo (PBO).1 We report interim data up to 28 weeks of the ongoing ELMWOOD OLE.Methods Patients completing the DBP on PBO, ELA 80mg, or ELA 120mg were eligible to enter the OLE and receive ELA 120mg. Endpoints were treatment-emergent adverse events (TEAEs) and mean change from DBP baseline in liver biochemistry and pruritus (per Worst-Itch Numeric Rating Scale [WI NRS]) to OLE Week (W)28, and in non-invasive tests (NITs) of fibrosis (enhanced liver fibrosis [ELF] and PRO-C3) to OLE W16.Results Of 64 patients who completed the DBP, 63 (98.4%) entered the OLE; 22 (100%) continued ELA 120mg treatment, and 20 (95.2%) and 21 (100%) crossed over from PBO and ELA 80mg in the DBP, respectively. At data cutoff (September 2024), TEAEs have been reported by 31/60 (51.7%) patients in the OLE; the most common TEAEs were COVID-19, nausea, pruritus, and weight increase (4/60 [6.7%] for each). TEAEs that led to treatment discontinuation have occurred in 3/60 (5.0%) patients (patient 1: diarrhea, nausea, and vomiting; patient 2: hepatocellular carcinoma; patient 3: nausea, pruritus, and agitation); all three patients had crossed over from PBO.Patients crossing over from PBO have had reductions in alkaline phosphatase (ALP) at OLE W4 (−36.1%; n=18) and W28 (−40.6%; n=5); patients initially on ELA 80mg and 120mg maintained ALP response or achieved further reductions to W28 (−35.6% [n=7] and −46.3% [n=8], respectively). At OLE W28, reductions have been seen in alanine aminotransferase, aspartate aminotransferase, total bilirubin, and γ-glutamyl transferase in patients crossing over from PBO (−21.0%, −2.5%, −10.0%, −16.9%; n=5); maintained response or further reductions have been seen in patients initially on ELA 80mg (−33.4%, −21.7%, −26.0%, −30.0%; n=7) and ELA 120mg (−27.5%, −6.5%, −17.0%, −37.2%; n=8).Reductions in WI NRS have been observed in all groups at OLE W28 (crossover PBO: −0.10; crossover ELA 80mg: −0.90; continuous ELA 120mg: −1.28). At OLE W16, patients initially on ELA 80mg or ELA 120mg have had further reductions in NIT of fibrosis (ELF: −0.16 and −0.15; PRO-C3: −20.6% and −14.4%); these markers have stabilized or reduced in patients initially on PBO (ELF: 0.05; PRO-C3: −9.3%).Conclusion(s) ELA 120mg has been well tolerated in patients with PSC in the ELMWOOD OLE. All groups show reductions in biochemical markers of cholestasis and pruritus. Patients crossing over from PBO show stabilization or reductions in NITs of fibrosis, while patients initially on ELA show further reductions in NITs of fibrosis with continued treatment.Reference Levy C, et al. J Hepatol. 2026;84:74–85.