The pan-PPAR agonist lanifibranor improves cardiometabolic health in patients with metabolic dysfunction-associated steatohepatitis

Michael P. Cooreman (), Javed Butler, Robert P. Giugliano, Faiez Zannad, Lucile Dzen, Philippe Huot-Marchand, Martine Baudin, Daniel R. Beard, Jean-Louis Junien, Pierre Broqua, Manal F. Abdelmalek and Sven M. Francque
Additional contact information
Michael P. Cooreman: Inventiva
Javed Butler: Baylor Scott and White Research Institute
Robert P. Giugliano: Harvard Medical School
Faiez Zannad: Université de Lorraine
Lucile Dzen: Inventiva
Philippe Huot-Marchand: Inventiva
Martine Baudin: Inventiva
Daniel R. Beard: Translational Medicine Academy
Jean-Louis Junien: Inventiva
Pierre Broqua: Inventiva
Manal F. Abdelmalek: Mayo Clinic
Sven M. Francque: Antwerp University Hospital and University of Antwerp

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract Lanifibranor, a pan-PPAR agonist, improves liver histology in patients with metabolic dysfunction-associated steatohepatitis (MASH), who have poor cardiometabolic health (CMH) and cardiovascular events as major mortality cause. NATIVE trial secondary and exploratory outcomes (ClinicalTrials.gov NCT03008070) were analyzed for the effect of lanifibranor on IR, lipid and glucose metabolism, systemic inflammation, blood pressure (BP), hepatic steatosis (imaging and histological grading) for all patients of the original analysis. With lanifibranor, triglycerides, HDL-C, apolipoproteins, insulin, HOMA-IR, HbA1c, fasting glucose (FG), hs-CRP, ferritin, diastolic BP and steatosis improved significantly, independent of diabetes status: most patients with prediabetes returned to normal FG levels. Significant adiponectin increases correlated with hepatic and CMH marker improvement; patients had an average weight gain of 2.5 kg, with 49% gaining ≥2.5% weight. Therapeutic benefits were similar regardless of weight change. Here, we show that effects of lanifibranor on liver histology in MASH are accompanied with CMH improvement, indicative of potential cardiovascular clinical benefits.

Date: 2024
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DOI: 10.1038/s41467-024-47919-9

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