P25 Elafibranor efficacy in primary biliary cholangitis according to biochemical response criteria in the phase III ELATIVE® trial

<h3></h3> ⁵Liver Institute Northwest, Seattle, USA <h3>Introduction</h3> In the phase III ELATIVE® trial (NCT04526665), the efficacy of elafibranor (a dual peroxisome proliferator-activated receptor-alpha/delta agonist) was assessed in patients with primary biliary cholangitis (PBC) and inadequate response or intolerance to ursodeoxycholic acid. PBC is characterised by elevated alkaline phosphatase (ALP) levels. During disease progression, total bilirubin (TB) levels increase. ALP and TB have prognostic value and form the basis of several clinical biochemical response criteria. The primary endpoint (POISE trial endpoint criteria: ALP &lt;1.67 x upper limit of normal [ULN], ALP reduction ≥15% from baseline and TB ≤ULN) was met by a significantly greater proportion of patients receiving elafibranor vs placebo (treatment benefit: 47.2%) at Week 52. Results from other binary biochemical response criteria, secondary outcomes in ELATIVE®, are presented here. <h3>Methods</h3> In the global, double-blind, placebo-controlled ELATIVE® trial, patients were randomised 2:1 to once-daily elafibranor 80mg or placebo. Biochemical response rates at Week 52 were analysed using POISE and: Paris I (ALP &lt;3 x ULN, aspartate aminotransferase [AST] &lt;2 x ULN and TB ≤1mg/dL); Paris II (ALP ≤1.5 x ULN, AST ≤1.5 x ULN and normal TB); Barcelona (ALP normalisation or reduction &gt;40% from baseline); Momah/Lindor (ALP ≤1.67 x ULN and TB ≤1mg/dL); and complete biochemical response (normal ALP, TB, AST, alanine aminotransferase, albumin and international normalised ratio) criteria. Rotterdam criteria (normalisation of TB and/or albumin) were used but are not reported as few patients had abnormal baseline TB or albumin (n=6). Exact Cochran-Mantel-Haenszel tests stratified by the randomisation factors were performed to examine the treatment benefit of elafibranor vs placebo. <h3>Results</h3> 161 patients received elafibranor (n=108) or placebo (n=53). Mean age was 57 (standard deviation: 9) years, and 96% of patients were female. Baseline ALP and TB levels were similar in each group. Responder rates consistently favoured elafibranor over placebo across Paris I (treatment benefit: 22.0%; odds ratio [OR]: 2.85; 95% confidence interval [CI]: 1.34–7.18; P=0.0061); Paris II (treatment benefit: 37.5%; OR: 16.65; 95% CI: 4.59–91.76; P&lt;0.0001); Barcelona (treatment benefit: 54.7%; OR: infinity; 95% CI: 20.22-infinity; P&lt;0.0001); and Momah/Lindor (treatment benefit: 42.8%; OR: 15.42; 95% CI: 4.60–50.00; P&lt;0.0001) criteria. A complete biochemical response was observed in 10 patients (9.3%) receiving elafibranor; none receiving placebo (OR: infinity; 95% CI: 1.51-infinity; P=0.0305). <h3>Discussion</h3> Elafibranor provided a consistent and significantly greater biochemical response in patients with PBC compared with placebo after one year of treatment using several prognostic scoring systems. Study sponsor: GENFIT; publication sponsor: Ipsen.