P23 Efficacy of elafibranor in primary biliary cholangitis: results from the variable double-blind period of ELATIVE®, a randomised, placebo-controlled phase III trial

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Introduction Primary biliary cholangitis (PBC) is a rare autoimmune cholestatic liver disease characterised by the destruction of interlobular bile ducts, resulting in cholestasis and biliary fibrosis. Elafibranor, a dual peroxisome proliferator-activated receptor-alpha/delta agonist, significantly improved prognostic biomarkers of cholestasis at Week 52 in patients with PBC in the phase III ELATIVE® trial.1 Here, we report the efficacy outcomes from ELATIVE® beyond Week 52. Methods In ELATIVE® (NCT04526665), patients with PBC and an inadequate response or intolerance to ursodeoxycholic acid, with alkaline phosphatase (ALP) ≥1.67 x upper limit of normal (ULN) and total bilirubin (TB) ≤2 x ULN, were randomised 2:1 to elafibranor 80mg or placebo once daily for ≥52 weeks. Patients continued their assigned regimen after Week 52 until all patients had completed the Week 52 visit or for a maximum of 104 weeks, whichever came first. We report efficacy outcomes beyond Week 52, during the variable double-blind period, with a focus on Week 78. Biochemical response, the primary endpoint at Week 52, was defined as ALP <1.67 x ULN, with ≥ 15% reduction from baseline, and TB ≤ULN. Data reported here are descriptive for patients with available data at Week 78. Results Among 161 randomised patients, 96/108 (89%) receiving elafibranor and 47/53 (89%) receiving placebo completed treatment to Week 52 (efficacy data reported previously1); 30/108 (28%) patients receiving elafibranor and 13/53 (25%) receiving placebo attended a Week 78 visit. At Week 78, the biochemical response endpoint was achieved in 19/27 (70%) patients receiving elafibranor compared with 0/13 (0%) patients receiving placebo. ALP normalisation occurred in 5/27 (19%) patients receiving elafibranor compared with 0/13 (0%) patients receiving placebo. Mean change from baseline to Week 78 in ALP was −135.3U/L in patients receiving elafibranor (n=26) versus 31.0U/L in patients receiving placebo (n=12). Mean change from baseline to Week 78 in TB was −1.2μmol/L in patients receiving elafibranor (n=25), while patients receiving placebo had a worsening of mean TB levels with an increase of 3.1μmol/L (n=12). Mean change from baseline to Week 78 in gamma glutamyl transferase (GGT) was −56.3U/L in patients receiving elafibranor (n=26) versus −10.3U/L in patients receiving placebo (n=12). Discussion Longer term treatment with elafibranor in patients with PBC through 78 weeks improved prognostic biomarkers of cholestasis beyond the positive efficacy outcomes previously reported through Week 52.1 Reference Kowdley KV. N Engl J Med. 2024;390(9):795–805. Study sponsor: GENFIT; secondary analysis and publication sponsor: Ipsen.

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