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

<h3>Introduction</h3> 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. <h3>Methods</h3> 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 &lt;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. <h3>Results</h3> 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). <h3>Discussion</h3> 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 <h3>Reference</h3> Kowdley KV. <i>N Engl J Med</i>. 2024;<b>390</b>(9):795–805. Study sponsor: GENFIT; secondary analysis and publication sponsor: Ipsen.