Gilead has presented promising Phase II results for its experimental NASH drug GS-0976, showing significant reductions in the build up of liver fat and a marker of fibrosis.
GS-0976 is an inhibitor of acetyl-coA carboxylase (ACC), which plays a role in one of several biologically relevant pathways associated with disease progression in NASH, catalysing the first step in the synthesis of fatty acids that contribute to hepatic steatosis (fat build-up in the liver) and, subsequently, inflammation and liver fibrosis.
In the trial, patients receiving the higher 20mg dose of the drug demonstrated statistically significant decreases in liver fat content (measured by MRI-PDFF) compared to placebo after 12 weeks of treatment (-28.9 versus -8.4, respectively).
A significant decrease in TIMP-1, a serum marker associated with liver fibrosis, was also observed, with -7.9 recorded for the treatment group and -1.5 for the placebo arm.
However, in other measures, including liver stiffness, serum ALT and PIII-NP, a serum marker of fibrogenesis, no statistically significant differences were observed between the treatment and placebo arms of the study, the firm said.
“In patients with advanced fibrosis, NASH may lead to severe complications including end-stage liver disease, hepatocellular carcinoma and the requirement for liver transplantation,” noted Rohit Loomba, MD, MHSc, lead study author, Director of the NAFLD Research Center, Director of Hepatology, Professor of Medicine, and Vice Chief of the Division of Gastroenterology at University of California San Diego School of Medicine.
“Unfortunately, there are no treatments available for these patients. In this first randomised, placebo-controlled, Phase II study of an ACC inhibitor in NASH, the data suggest that GS-0976 has the potential to play an important role in treating patients with this disease.”
The data were presented at The Liver Meeting 2017 in Washington, DC.