Long-term efficacy and safety of elafibranor in primary biliary cholangitis: Interim results from the open-label extension of the ELATIVE trial up to 3 years

Background: Elafibranor (ELA) significantly improved biomarkers of cholestasis at Week (W)52 in patients (pts) with primary biliary cholangitis (PBC) in the phase III ELATIVE trial (NCT04526665).

Aim: To report up to 3-year interim results from the ongoing ELATIVE open-label extension (OLE).

Method: Pts completing the ELATIVE double-blind period (DBP) were eligible to enter the OLE receiving ELA 80 mg daily. For pts who received placebo (PBO) in the DBP, baseline (BL) was set as the last non-missing value before the first OLE ELA dose; for pts who received ELA in the DBP, BL was the DBP start. Endpoints reported include biochemical response (alkaline phosphatase [ALP]<1.67xULN, 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;safety analyses evaluated events in the OLE.

Result: At data cutoff (June 2024), 153 pts had received ELA; 108 received ELA and 45 received PBO in the DBP. 138 pts entered the OLE. Pts receiving continuous ELA had data up to W156. At BL for each group, pts crossing over from PBO had increased mean ALP and TB vs pts receiving continuous ELA (335.8U/L vs 321.3U/L; 0.64mg/dL vs 0.57mg/dL).In pts receiving continuous ELA, 34/61(56%) at W104 and 11/13(85%) at W156 had biochemical response; ALP normalization occurred in 8/61(13%) at W104 and 5/13(39%) at W156. In pts crossing over from PBO, 21/41(51%) had biochemical response and 9/41(22%) had ALP normalization at W52. LSM and ELF scores showed a trend for stability in pts receiving continuous ELA for≥104 weeks (median change from BL in LSM: W104:−0.2 kPa[n=48],W156:−0.5 kPa[n=11];ELF:W104:0.0[n=41],W156:−0.6[n=9]).Improvement in pruritus was sustained in pts with moderate-to-severe pruritus at BL receiving continuous ELA (mean change from BL in PBC WI-NRS:W104:−3.1[n=21], W156:−4.4[n=5]; PBC-40 Itch: W104:−3.0[n=22],W156:−4.6[n=5]; 5-D Itch:W104:−5.0[n=22], W156:−7.0[n=5]). No new safety signals were identified.

Conclusion: In the ongoing ELATIVE OLE, ELA led to sustained improvements in biomarkers of cholestasis and pruritus and stabilization of fibrosis up to W156 and remained well tolerated. Pts crossing over from PBO had similar results at W52 to those who received ELA in the DBP.

 

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Publication History

Article published online:
04 September 2025