Abstract
IntroductionElafibranor significantly improved biomarkers of cholestasis at Week 52 in patients with primary biliary cholangitis (PBC) in the phase III ELATIVE® trial (NCT04526665). We report up to 3-year interim results from the ongoing ELATIVE® open-label extension (OLE).MethodsPatients completing the ELATIVE® double-blind period (DBP) were eligible to enter the OLE receiving elafibranor 80 mg daily. For patients who received placebo (PBO) in the DBP, baseline (BL) was set as the last non-missing value before the first OLE elafibranor dose, for patients who received elafibranor in the DBP, BL was the DBP start. Endpoints reported include biochemical response (alkaline phosphatase [ALP] <1.67 x ULN, with ≥15% reduction from BL and total bilirubin [TB] ≤ULN), ALP normalization, change in liver stiffness measurement (LSM) and enhanced liver fibrosis (ELF) score, and change in pruritus (PBC Worst Itch Numeric Rating Scale [WI-NRS], PBC-40 Itch, and 5-D Itch) in those with moderate-to-severe pruritus at BL (PBC WI-NRS ≥4). Results presented descriptively, and safety analyses evaluated events in the OLE.ResultsAt data cutoff (June 2024), 153 patients had received elafibranor, 108 received elafibranor and 45 received PBO in the DBP. 138 patients entered the OLE. Patients receiving continuous elafibranor had data up to Week 156. At BL for each group, patients crossing over from PBO had increased mean ALP and TB versus patients receiving continuous elafibranor (335.8 U/L versus 321.3 U/L, 0.64 mg/dL versus 0.57 mg/dL).In patients receiving continuous elafibranor, 34/61 (56%) at Week 104 and 11/13 (85%) at Week 156 had biochemical response, ALP normalization occurred in 8/61 (13%) at Week 104 and 5/13 (39%) at Week 156. In patients crossing over from PBO, 21/41 (51%) had biochemical response and 9/41 (22%) had ALP normalization at Week 52. LSM and ELF scores showed a trend for stability in patients receiving continuous elafibranor for ≥104 weeks (median change from BL in LSM: Week 104: −0.2 kPa [n=48], Week 156: −0.5 kPa [n=11], ELF: Week 104: 0.0 [n=41], Week 156: −0.6 [n=9]). Improvement in pruritus was sustained in patients with moderate-to-severe pruritus at BL receiving continuous elafibranor (mean change from BL in PBC WI-NRS: Week 104: −3.1 [n=21], Week 156: −4.4 [n=5], PBC-40 Itch: Week 104: −3.0 [n=22], Week 156: −4.6 [n=5], 5-D Itch: Week 104: −5.0 [n=22], Week 156: −7.0 [n=5]). No new safety signals were identified.Conclusion(s)In the ongoing ELATIVE® OLE, elafibranor led to sustained improvements in biomarkers of cholestasis and pruritus and stabilization of fibrosis up to Week 156 and remained well tolerated. Patients crossing over from PBO had similar results at Week 52 to those who received elafibranor in the DBP.Study FundingPublication sponsorIpsen; study sponsors: Ipsen/GENFIT.