Long-Term Efficacy and Symptom Relief With Elafibranor in PBC, With Andreas Kremer, MD, PhD

Management of symptoms in primary biliary cholangitis (PBC) has long been one of the most challenging aspects of care. While existing therapies have proven their efficacy for slowing disease progression and reducing cholestasis, many patients continue to struggle with burdensome symptoms of pruritus and fatigue.

Treatment options for these symptoms have been limited, largely off-label, and often hampered by safety, tolerability, or drug-drug interaction concerns. As clinicians become more attentive to patient-reported outcomes, it has become increasingly evident that many patients have not received adequate care for their high symptom burden.

“Historically, we have not managed these symptoms well. We have not asked our patients intensively, because our therapeutic arsenal was very much limited,” Andreas Kremer, MD, PhD, the head of hepatology at University Hospital Zurich, explained to HCPLive.

Against this backdrop, the emergence of novel peroxisome proliferator-activated receptor (PPAR) agonists offers a meaningful step forward. Among them, elafibranor, a dual PPAR-α/δ agonist, has generated significant interest due to its dual impact on biochemical response and symptom improvement, as emphasized in data from multiple abstracts presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025.

BMI and Elafibranor Efficacy

The first study examined the effect of BMI on elafibranor pharmacokinetics and its efficacy in healthy, overweight, and obese subgroups of the phase 3 ELATIVE trial and found BMI had no clinically relevant effect on exposure to elafibranor or GFT1007 in patients with PBC. Additionally, in the elafibranor arm of ELATIVE, biochemical response rates at week 52 were 56.3%, 46.4% and 44.8% in the healthy weight, overweight and obese subgroups, respectively. Mean changes in ALP levels from baseline to week 52 in the elafibranor arm were –41.5%, –41.8% and –32.3% for elafibranor in the healthy weight, overweight and obese subgroups respectively.

Association Between Symptoms and Cholestatic Biomarkers

Another abstract presented at AASLD assessed the association between improvements in symptoms and cholestatic biomarkers. At baseline, 46/108 and 58/108 patients receiving elafibranor and 20/53 and 30/53 receiving placebo had moderate to severe fatigue according to PFSF 7a and PBC-40 Fatigue scores, respectively. Improvements in PFSF 7a scores were seen within 4 weeks with elafibranor compared with placebo (mean change from baseline, −3.7; SE, 0.9 vs −0.7; SE, 0.9), with further improvements to week 52 (−6.5; SE, 1.2 vs −2.6; SE, 1.6). Changes in PBC-40 Fatigue scores with elafibranor were similar to placebo at week 4 (−2.7; SE, 0.7 vs −2.6; SE, 1.1) but improved to week 52 (−3.6; SE, 1.0 vs −2.1; SE, 1.0).

At baseline, 44/108 patients receiving elafibranor and 22/108 receiving placebo had moderate to severe pruritus. PBC-40 Itch and 5-D Itch improved within 4 weeks with elafibranor versus PBO (−1.4; SE, 0.5 and −2.9; SE, 0.7 vs −0.6; SE, 0.4 and −1.7; SE, 0.8) and continued to week 52 (−2.5; SE, 0.5 and −4.3; SE, 0.7 vs −0.2; SE, 0.7 and −1.7; SE, 1.0).

Proteomic Research on Elafibranor and Fatigue

A third abstract presented at AASLD builds upon a previous analysis presented at the European Association for the Study of the Liver (EASL) Congress 2025, examining the relationship between changes in expression of 10 proteins with a potential role in fatigue or mitochondrial function and fatigue severity with elafibranor. In the study, investigators assessed serum samples collected from patients in the phase 3 ELATIVE trial at baseline and week 52.

Results showed treatment with elafibranor led to expression changes of proteins linked to fatigue or mitochondrial function, significantly correlated with each other and with fatigue improvement and suggesting that PPARα/δ agonism beneficially impacts fatigue-associated pathways linked to mitochondrial function.

“We have seen more and more data that long term safety and efficacy is present for this drug,” Kremer told HCPLive. “It works for up to several years in regard to the anticholestatic and anti-inflammatory properties as measured by laboratory parameters, and we see a long term efficacy in symptom burden improvement, which is very reassuring for such a drug.”

Editors’ Note: Relevant disclosures for Kremer include AbbVie, AstraZeneca, Bayer, CymaBay, Gilead, GlaxoSmithKline, Intercept, Mirum, Takeda, Ipsen, and others.

References

1. Kremer A, Levy C, Bowlus C, et al. The efficacy of elafibranor is not affected by body mass index in patients with primary biliary cholangitis. Presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025. Washington, DC. November 7-11, 2025.

2. Kremer A, Jones D, Levy C, et al. Changes in fatigue and pruritus in patients with primary biliary cholangitis treated with elafibranor are largely independent from improvements in serum biomarkers. Presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025. Washington, DC. November 7-11, 2025.

3. Brooks A. Elafibranor Benefits Fatigue-Related Pathways Linked to Mitochondrial Function in PBC. HCPLive. November 9, 2025. Accessed November 11, 2025. https://www.hcplive.com/view/elafibranor-benefits-fatigue-related-pathways-linked-mitochondrial-function-pbc