What can we expect from PPAR agonists in the treatment of NASH?
PPAR (Peroxisome proliferator-activated receptor) agonists have great promise in the therapeutic landscape of NASH (Non-alcoholic steatohepatitis). The role of PPARs in general have been demonstrated to have a significant role in lipid metabolism, glucose metabolism, inflammation, endothelial revascularization as well as the activation of hepatic stellate cells. So the therapeutic landscape of PPARs in the treatment of NASH has already demonstrated not only for the improvement in the cardio metabolic profile of a patient with NASH, but we’ve learned in use of pioglitazone both in diabetics and non-diabetics that the use of pioglitazone has had an improvement in necro inflammation of NASH greater than two point reduction in the Na score without worsening of fibrosis as well as NASH resolution both in diabetes and non-diabetes.We also learned from the dual PPARS.
Lanifibranor; a pan-PPAR agonist
Lanifibranor which is a PPAR alpha delta compound in the golden 505 trial. The use of Lanifibranor or dose of 120 milligrams for a duration of a year improved NASH and patients who at baseline had a NASH activity score of greater than or equal to four. We’re also very excited about the role of PPARS; Lanfibranor which will have the ability to work on lipid metabolism and glucose metabolism. The gamma element of the PPAR can have a direct liver anti-inflammatory effect on the liver and potentially even on fibrosis. Lanifibranor is currently in phase two clinical trial.So time will tell what the outcome of that but generally the signal even in meta analysis that evaluated PPARS as a class for the treatment of NAFLD to NASH have demonstrated an anti-steatotic, anti-inflammatory and have promised to potentially demonstrate an anti-fibrotic benefit.