Icosabutate reduces relevant markers, fibrosis in NASH

Icosabutate improved markers of liver injury, inflammation and fibrosis in patients with nonalcoholic steatohepatitis, according to a study presented at the International Liver Congress.

“Icosabutate (ICO) is a pharmaceutically modified fatty acid based on the N-3 polyunsaturated fatty acid structure where the chemical modification prevents it from being incorporated into triglyceride particles easily in the intestines, so it gets absorbed directly into the portal vein and thus increases liver exposure,” Arun Sanyal, MD, Virginia Commonwealth University, said. “It shuts down the production of lipoxygenase ... which are specifically increased in NASH.”

In a placebo-controlled, phase 2b study, researchers dosed 90 patients with NASH with either ICO 300 mg, ICO 600 mg or placebo through 16 weeks to assess biomarkers of liver injury, inflammation, fibrogenesis, glycemic control and lipid metabolism. According to interim analysis results, there were rapid, sustained and significant dose-dependent decreases among both dosage groups in alanine aminotransferase (–19 U/L and –25.4 U/L, respectively), aspartate aminotransferase (–9.4 U/L and –13.5 U/L), gamma-glutamyl transpeptidase (–16.9 U/L and –28.6 U/L) and alkaline phosphatase (–12.7 U/L and –19.6 U/L). Researchers noted patients dosed with ICO 600 mg also had significant reductions in PRO-C3 (–4.6 ng/mL) and enhanced liver fibrosis score (–0.6) as well as a 52% decrease in high-sensitivity C-reactive protein. Overall, treatment was well tolerated among all groups.

“This drug works on the interface of oxidative stress of which is inflammation fibrosis, and all of those downstream elements did show improvement while the steatosis did not really change,” Sanyal said. “We are very encouraged by these initial findings, but of course the final proof will come when we have the histology data for the full trial at the end of 1 year.”