Fatty acid synthase inhibitor reduces liver fat, markers of liver injury in NASH

TVB-2640, a fatty acid synthase inhibitor, significantly reduced liver fat and serum biomarkers of liver injury, fibrosis and inflammation in patients with nonalcoholic steatohepatitis according to research presented at The Digital International Liver Congress.

“Once daily, oral tablet of TVB-2640 appeared to be well-tolerated and had a good safety profile,” Rohit LoombaMD, MHSc, from the division of gastroenterology at the University of California at San Diego, said during his presentation. “[We] believe that these data provide justification for examining the efficacy of TVB-2460 in improving NASH resolution and fibrosis in biopsy-proven NASH patients.”

In a phase 2 trial, Loomba and colleagues randomly assigned 99 patients to either placebo or TVB-2640 (Sagimet Biosciences) at 25 mg or 50 mg daily in sequential cohorts, for 12 weeks. Changes in liver fat content by MRI- PDFF (proton density fat fraction) and percentage of patients with approximately a 30% decrease in liver fat at 12 weeks served as primary endpoints. Other endpoints included the effect on safety evaluations, serum ALT and AST, cholesterol, triglycerides, lipoproteins, eicosanoids and liver fibrosis markers.

According to researchers, most patients were Hispanic and 75% had diabetes. Twelve weeks of treatment with 25 mg TVB-2640 reduced liver fat with a mean relative difference of 18.2% compared with placebo. Seven patients treated with TVB-2640 achieved a 30% or more relative decrease.

“The mean relative liver fat reduction by week 12 by MRI-PDFF was 28.2% in the 50 mg group relative to placebo, which is an increase of 4.5%,” Loomba said. “There was a clear dose response.”

Loomba and colleagues observed a reduction in mean serum ALT in MRI-PDFF responders compared with a 9.3% increase in non-responders. In addition, responders showed a decrease in serum fibrosis and inflammation biomarkers. Plasma tripalmitin and reductions in liver fat showed a decreasing trend as well.

According to Loomba, no serious adverse events were reported, and any adverse events noted were mostly grade 1 or mild.