Elafibranor Shows Sustained Long-Term Efficacy and Safety in PBC: New 2-Year Placebo-Controlled and 3-Year Extension Data

Key Takeaway

In the phase III ELATIVE trial, elafibranor maintained robust biochemical efficacy in patients with PBC and inadequate response or intolerance to UDCA, with 64.3% achieving biochemical response at Week 104 versus 0% with placebo. Longer-term open-label data showed sustained responses through 156 weeks, stable non-invasive fibrosis measures, numerical improvements in fatigue and pruritus, and no new safety signals with exposure up to 182 weeks.

Why It Matters

What changed: The pivotal 52-week ELATIVE data established elafibranor’s efficacy; these results now provide the longest placebo-controlled follow-up reported for an approved PBC therapy, extending randomized data to 104 weeks and treatment observations to approximately 3 years. Biochemical response remained durable, while patients crossing from placebo reproduced the treatment effect after starting elafibranor.

Who it applies to: Patients with PBC who have an inadequate response or intolerance to UDCA, particularly those requiring long-term second-line therapy. Nearly all trial participants were receiving concomitant UDCA.

Does it change practice? Not immediately, the study does not establish a new indication or treatment algorithm. Rather, it strengthens confidence in long-term elafibranor use, showing that its biochemical benefit does not appear to attenuate with time and that longer exposure has not revealed an important new safety signal. The symptom findings are encouraging, particularly for pruritus, but remain supportive rather than definitive.

Limitations: Later time points included substantially fewer patients, only 28 elafibranor and 11 placebo patients remained at Week 104, and just 20 continuous-treatment patients contributed Week-156 biochemical data. The open-label extension was an exploratory snapshot rather than a prespecified interim analysis, with potential survivor/informative-dropout bias; symptom analyses involved small subgroups, and stable LSM/ELF should not be interpreted as evidence of an antifibrotic effect.

Bottom Line

Elafibranor’s biochemical response appears durable through approximately 3 years, with reassuring longer-term tolerability and no evidence of efficacy waning. These data reinforce its role as a long-term second-line PBC therapy, but they do not yet demonstrate improved fibrosis or clinical outcomes.

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Kowdley KV, Bowlus CL, Levy C, et al. J Hepatol. Published online August 27, 2026. doi:10.1016/j.jhep.2026.08.016