Now we move to PPAR (peroxisome proliferator-activated receptors) Alpha Delta agonist – the dual agonist Elafibranor. Elafibranor was targeted to patients with NASH (non-alcoholic steatohepatitis) without cirrhosis. In their phase 2 studies, there were 40% diabetic and Elafibranor 80 milligrams or 120 milligrams studied. They’ll note the type of the twelve should be 120 milligrams versus Placebo. There were 90 patients per group and they studied for one year. So, a very nice favorable effect on LDL cholesterol, reduced by 30 milligram per deciliter and that would correspond to 20% to 30% reduction. That’s really superb, almost like a low intensity statin response. Triglyceride went down by 20 milligram per deciliter and HDL went up by a small amount. They found that Hemoglobin A1c decreased by higher doses in that diabetic subgroup. Free fatty acids Fibrinogen insulin all decreased but most not dose dependent.
Elafibranor: Primary & secondary outcomes
So the primary outcome was the resolution of NASH without fibrosis, worsening by liver biopsy that was not achieved in the total group. However, there were more favorable results with the post-hoc modified outcome. That’s actually considered a more rigorous outcome. In a post time subgroup with high NAFLD (non-alcoholic fatty liver disease) activity. The idea then would be one with more active people with more active disease who would respond to the treatment.
Now the RESOLVE-IT study; the interim results were reported by the company GENFIT. So they enrolled patients with NASH or at risk for NASH with fibrosis by biopsy a high NASH score and the Fibrosis score of between 1 to 4 moderate. So Elafibranor 120mg was studied and with the intention to treat cohorts, there are over a thousand participants. 2:1 Elafibranor and Placebo. The primary outcome was resolution of NASH without increase in Fibrosis measured at 72 weeks or later or total mortality or liver disease or Cirrhosis. So the results were somewhat disappointing as the primary liver outcome – there was 19% in the Placebo group versus 24% in the Elafibranor and the P-value was .066 which is not significant. However, that might be considered a trend worth continuing. The secondary outcome of Fibrosis was in 22% of Placebo versus 24% Elafibranor though not significant or trending at all. It was reported without showing the data that there was no effect on lipids hemoglobin A1c in the diabetics. Now this study is being evaluated very closely and we’ll see more as these studies continue.