Long-Term Elafibranor Treatment Leads to Biochemical, Symptomatic Improvements in PBC

New data from the ongoing ELATIVE open-label extension study highlight elafibranor’s long-term ability to improve liver health biomarkers, stabilize fibrosis, and reduce fatigue and itching symptoms in patients with primary biliary cholangitis (PBC).1

Jörn Schattenberg, MD, a director of the department of internal medicine II at Saarland University Medical Center, presented the findings at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025. The results demonstrated rapid, sustained, and reproducible responses in clinically relevant biomarkers of cholestasis and fibrosis as well as positive effects on cholestasis, sustained improvement in pruritus and fatigue, stabilization of markers of fibrosis.

“PBC does not impact all patients in the same way. Therefore, it is important for us to have access to data associated with long-term treatment benefit on the disease biomarkers and liver tests, as well as a positive impact on symptoms. These preliminary results, which indicate a potential improvement not only in pruritus, but also in fatigue, are very encouraging,” said. Cynthia Levy, MD, a professor of Medicine, Division of Digestive Health and Liver Diseases, at the University of Miami in a statement. “We need to regularly monitor our patients with PBC over their lifetime and this data from the ELATIVE trial confirms that elafibranor is an effective treatment, with a reassuring, well-characterized safety profile, over the long-term.”2

Elafibranor, a dual peroxisome proliferator-activated receptor-α/δ (PPARα/PPARδ) agonist, received accelerated approval from the US Food and Drug Administration (FDA) in June 2024 as a second-line therapy for adults with PBC who had an inadequate response or were unable to tolerate first-line ursodeoxycholic acid. The decision was based on results from the phase 3, multicenter, randomized, double-blind, placebo-controlled ELATIVE trial, which demonstrated significant reductions in ALP and favorable safety outcomes with elafibranor 80 mg once daily.3

In the phase 3 trial, 153 patients with PBC were randomly assigned into elafribanor 80 mg (n = 108) or placebo (n = 45) groups. The open-label extension enrolled these participants contingent upon completion of the trial’s double-blind period. For placebo recipients, baseline was defined as the last non-missing value before their first elafibranor dose. Those previously treated with elafibranor continued 80 mg once daily. In total, 138 patients enrolled in the open-label extension, and 115 remained through the May 2025 data cutoff.

Primary endpoints included biochemical response (ALP <1.67x upper limit of normal [ULN], with ≥15% reduction from baseline, and total bilirubin [TB] ≤ ULN), ALP normalization, and change in ALP, TB, albumin, gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), liver stiffness measurement (LSM), and enhanced liver fibrosis (ELF) score. Fatigue and pruritus were assessed in patients with baseline moderate to severe symptoms, defined by a Patient-Reported Outcomes Measurement Information System (PROMIS) T-score ≥60 or a Primary Biliary Cholangitis–40 (PBC-40) itch domain numeric rating scale (NRS) ≥4.

The findings presented at AASLD show sustained biochemical response rates in 72.1% of patients (31/43) through week 182, or >3 years into the study. Improvement in ALP occurred as early as week 4. By week 182, > 60% of patients had reductions of ≥40% from baseline (week 182: 67.4%; mean change in ALP, −47.1%), and 18.6% of patients (8/43) showed sustained normal ALP levels by week 182.

Biomarkers of hepatic function, such as TB and albumin, reported no significant change, while GGT and ALT decreased. Investigators noted the stabilization of fibrosis markers, LSM, and ELF. At week 4, there was an improvement of PROMIS-T-scores sustained to week 156 in those with moderate to severe fatigue (n = 25; mean, −8.5; standard deviation [SD], 10.3). Similarly, there was marked improvement in moderate to severe pruritus (n = 23; mean −4.1; SD, 2.3).

“In the ongoing ELATIVE® OLE, [elafibranor] has led to rapid, sustained, and reproducible responses in clinically relevant biomarkers of cholestasis and fibrosis, suggesting potential for slowing disease progression,” wrote Schattenberg and colleagues. “Positive effects on cholestasis, sustained improvement in pruritus and fatigue, stabilization of markers of fibrosis, and a consistent safety profile confirm ELA’s suitability for long-term PBC treatment.”

References

1. Schattenberg JM, Levy C, Akarca U, et al. Long-Term Outcomes of Elafibranor in the ELATIVE Open-Label Extension Study. Presented at: AASLD The Liver Meeting 2025; Nov 7–11, 2025; Washington, DC.

2. Ipsen. Ipsen to present two late‑breaking sessions at AASLD on new PBC data supporting IQIRVO®’s long‑term efficacy, safety, and mechanistic insights in fatigue. Ipsen; November 7, 2025. Accessed November 11, 2025. https://www.ipsen.com/press-releases/ipsen-to-present-two-late-breaking-sessions-at-aasld-on-new-pbc-data-supporting-iqirvos-long-term-efficacy-safety-and-mechanistic-insights-in-fatigue-3183662/

3. Kowdley KV, Bowlus CL, Levy C, et al. Efficacy and safety of elafibranor in primary biliary cholangitis. N Engl J Med. 2024;390(9):795‑805. doi:10.1056/NEJMoa2306185