Gilead presents data from proof-of-concept study in NASH patients
Gilead Sciences presented today data from a proof-of-concept study of investigational combination therapies for patients with advanced fibrosis due to nonalcoholic steatohepatitis, combining the apoptosis signal-regulating kinase 1 inhibitor selonsertib with either the Acetyl-CoA carboxylase inhibitor GS-0976 or the selective, non-steroidal Farnesoid X receptor (FXR) agonist GS-9674. The data were presented at The International Liver Congress 2018 in Paris. More than 25 additional Gilead abstracts on NASH and other fibrotic liver diseases are also being presented, including data from predictive modeling studies using noninvasive tests for the diagnosis and monitoring of NASH that aim to reduce the need for liver biopsy. The proof-of-concept study included 70 patients. All patients in the study were diagnosed with NASH and liver fibrosis stages F2 to F3 based on biopsy, or by magnetic resonance elastography and MRI proton density fat fraction. The greatest changes observed after 12 weeks of treatment in the study were decreases in liver fat content, which occurred in regimens containing GS-0976. Improvements in liver biochemistry and/or markers of fibrosis were also observed across both combination arms of the study compared to baseline, the company said. In patients treated with selonsertib plus GS-0976, kinetic labeling revealed the largest reduction in the fractional synthesis rate of lumican, a marker of fibrogenesis. Similar rates of adverse events were observed between patients treated with single-agent and combination therapies. No patient discontinued treatment prematurely. "These encouraging results suggest that combination therapy with selonsertib and either GS-0976 or GS-9674 warrants further exploration in longer-term studies in patients with NASH and F3 and F4 fibrosis," said Stephen Harrison, MD, presenting author and Visiting Professor of Hepatology at the Radcliffe Department of Medicine, University of Oxford, UK. "Patients with advanced fibrosis due to NASH urgently need effective therapeutic options because they may face more serious health risks, including development of complications of end-stage liver disease, liver cancer and the need for liver transplantation. Combination therapy may be a way forward to achieving greater benefit for this patient population."