Inventiva announced the publication of results in Journal of Hepatology Reports from its Phase 2b NATIVE clinical trial and preclinical studies, evaluating lanifibranor's effects on liver sinusoidal endothelial cells (LSECs) in MASLD and MASH. The study showed that LSEC capillarization, a key driver in liver disease progression, was associated with fibrosis and inflammation in MASLD/MASH patients.
Treatment with lanifibranor for 24 weeks in the NATIVE trial resulted in a dose-dependent reduction of CD34 staining on liver biopsies, suggesting a decrease in LSEC capillarization. Preclinical models further demonstrated that lanifibranor's effects extend beyond capillarization reversal, normalizing intrahepatic vascular resistance (IHVR) and portal vein pressure.
These findings indicate that lanifibranor's pan-PPAR agonist mechanism may prevent portal hypertension by addressing both intra-hepatic conditions like fibrosis and LSEC dysfunction, as well as extra-hepatic conditions such as mesenteric vasculature expansion. The observed effects were superior to those seen with single PPAR agonists, reinforcing lanifibranor's potential to prevent progression to cirrhosis.
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