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

Background: Elafibranor, a dual peroxisome proliferator-activated receptor-α/δ agonist, is being investigated in primary biliary cholangitis (PBC). In the phase III ELATIVE trial (NCT04526665), elafibranor efficacy was assessed in patients with PBC with inadequate response or intolerance to ursodeoxycholic acid. PBC is characterised by elevated alkaline phosphatase (ALP) levels. As the disease progresses, total bilirubin (TB) levels increase. ALP and TB have prognostic value and form the basis of several clinical biochemical response criteria.

Aim: The primary endpoint (POISE trial endpoint criteria: ALP<1.67 x upper limit of normal [ULN], ALP reduction ≥15% from baseline [BL] and TB at or below 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.

Method: In the global, double-blind, placebo-controlled ELATIVE trial, patients were randomised 2:1 to once-daily elafibranor 80 mg or placebo. Biochemical response rates at Week 52 were analysed using POISE and Paris I;Paris II;Barcelona;Momah/Lindor; and complete biochemical response (normal ALP, TB, AST, alanine aminotransferase, albumin and international normalised ratio) criteria. Rotterdam criteria were used but are not reported as few patients had abnormal BL 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.

Results: 161 patients received elafibranor (n=108) or placebo (n=53). BL 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<0.0001);Barcelona (treatment benefit:54.7%;OR: infinity; 95% CI:20.22–infinity; p<0.0001);and Momah/Lindor (treatment benefit:42.8%;OR:15.42;95% CI:4.60–‍50.00; p<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).

Conclusion: 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.

präsentiert in der Sitzung: Autoimmunität und IgG4 vermittelte Erkrankungen im GI-Trakt

Freitag, 04. Oktober 2024, 10:30 – 12:00, Saal 5

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Artikel online veröffentlicht:
26. September 2024