In a phase-2a clinical trial, the drug, now known as TVB-2640, significantly reduced excess liver fat and improved metabolic, inflammatory and fibrotic markers.
Sagimet Biosciences is developing the drug and funded the study. The U.S. Food and Drug Administration (FDA) granted TVB-2640 fast track designation for the treatment of NASH in March 2021 (https://bit.ly/3C3VHLs).
The FASCINATE-1 trial enrolled 99 adults with NASH and at least 8% liver fat and evidence of liver fibrosis. Participants were randomly allocated to placebo or 25 mg or 50 mg of TVB-2640, taken once daily by mouth for 12 weeks.
Over the 12 weeks, treatment with TVB-2640 led to significant, dose-dependent reductions in liver fat (the primary outcome) as assessed by MRI-proton density fat fraction (MRI-PDFF) imaging. The reduction in liver fat was 9.6% (P=0.053) with 25 mg TVB-2640 and 28.1% (P=0.001) with 50 mg cohort versus a 4.5% increase with placebo.
In addition, 23% of patients taking 25 mg TVB-2640 and 61% taking 50 mg (P<0.001) achieved at least a 30% relative reduction in liver fat compared with 11% of patients taking placebo, the study team led by Dr. Rohit Loomba of the University of California, San Diego, reports in Gastroenterology.
"TVB-2640 also elicited a rapid impact on de novo lipogenesis (DNL), hepatic fat, blood levels of pro-inflammatory/pro-fibrotic lipotoxic metabolites and markers of fibrogenesis, indicating the mechanism of action of this drug across multiple pathologic pathways," the company said in a news release.
"In contrast, the placebo population showed increases in liver fat, liver enzymes, liver cell injury, and cholesterol levels over the 12 weeks. Future studies will determine if a longer duration of treatment will result in an even greater response," it added.
"It is imperative that therapies either regress fibrosis or blunt the progression of it. Our data indicate TVB-2640's potential is two-fold: first, it reduces lipotoxic liver injury that drives fibrosis-inducing damage; and second, it has a direct effect on inflammatory stimuli and stellate cells in the liver," Dr. Loomba, who has financial ties to Sagimet, said in the news release.
"The positive results based on the 12-week study provide a compelling foundation for larger randomized clinical trials with histological endpoints. We are excited to continue the path towards finding a treatment for NASH patients, including the near-term initiation of the Phase 2b FASCINATE-2 trial," he added.
SOURCE: https://bit.ly/3BXEnaE Gastroenterology, online July 23, 2021.
By Reuters Staff
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