TVB-2640 impresses in nonalcoholic steatohepatitis

Use of the fatty acid synthase (FASN) inhibitor TVB-2640 in the treatment of patients with nonalcoholic steatohepatitis (NASH) yields dose-dependent improvements in liver fat as well as biochemical, inflammatory, and fibrotic biomarkers, according to the results of the phase IIa trial 3V2640-CLIN-005 (FASCINATE-1).

FASCINATE-1 randomized 99 adult patients with NASH to receive TVB-2640 at 25 or 50 mg or placebo orally, once-daily for 12 weeks. All patients had ≥8 percent liver fat and evidence of liver fibrosis, as assessed by MRI-proton density fat fraction and MR-elastography or liver biopsy.

At week 12, the efficacy endpoint of liver fat decreased with TVB-2640, specifically by 9.6 percent in the 25-mg arm (n=30; least squares mean [LSM], –15.5 percent, 95 percent confidence interval [CI], –31.3 to –0.23; p=0.053) and by 28.1 percent in the 50-mg arm (n=28; LSM: –28.0 percent, 95 percent CI, –44.5 to –11.6; p=0.001). On the other hand, liver fat increased by 4.5 percent in the placebo arm.

Moreover, the number of patients who achieved a ≥30-percent relative reduction in liver fat was significantly higher in the active treatment arms than in the placebo arm (23 percent with 25 mg and 61 percent with 50 mg vs 11 percent; p<0.001).

Secondary analyses revealed improvements in metabolic, pro-inflammatory, and fibrotic markers.

In terms of safety, TVB-2640 was well tolerated. Adverse events were mostly mild in severity and did not significantly differ across the three treatment arms.