SAN FRANCISCO — Results from a phase 2b trial showed that Aramchol— a stearoyl coenzyme desaturase A inhibitor — significantly reduced liver fat and improved histology with excellent safety and tolerability in patients with nonalcoholic fatty liver disease, according to data presented at The Liver Meeting 2018.
“Aramchol is a novel, first in class SCD1 modulator, targeted to the liver to reduce liver fat and collagen production,” Vlad Ratziu, MD, from Sorbonne University in France, said in his presentation. “In 1 year of study, Aramchol showed liver fat reduction, biochemical improvement, NASH resolution and fibrosis reduction in a dose response pattern.”
To assess the safety and efficacy of Aramchol (arachidyl amido cholanoic acid; Galmed Pharmaceuticals) for reduction of liver fat, Ratziu and colleagues enrolled 247 patients with overweight or obesity and prediabetes or diabetes who had biopsy-proven NASH.
The researchers randomly assigned patients to receive either 400 mg (n = 101) or 600 mg (n = 98) of Aramchol or placebo (n = 48). They assessed liver fat by magnetic resonance spectroscopy.
At 1 year follow-up, liver fat was significantly reduced in the 400 mg group (P = .045) and showed a nearly significant trend in the 600 mg group (P < .066) compared with placebo. The researchers observed an absolute reduction from baseline of 5% or higher in 47% of patients in the 600 mg group vs. 24% in the placebo group (OR = 2.77; 95% CI, 1.12-6.89) and 37% in the 400 mg, which “suggests a dose response,” Ratziu said.
NASH resolution without worsening of fibrosis occurred more often in the 600 mg group than the placebo group (16.7% vs. 5%; OR = 4.74; 95% CI, 0.99-22.66).
Both dose groups experienced significantly reduced alanine aminotransferase (P < .001), aspartate aminotransferase (P = .002) and HbA1c (P < .001) compared with placebo in a dose response manner.
Discontinuation due to adverse events was less than 5% and serious adverse events occurred in 10% of patients without a difference between dose groups. Weight remained neutral throughout the trial and no patients experienced changes in lipid parameters.
“Results place Aramchol 600 mg among advanced therapeutic candidates for NASH and support further testing in a phase 3 trial,” Ratziu concluded.
Ratziu V, et al. Abstract LB-5. Presented at: The Liver Meeting 2018; Nov. 9-13, 2018; San Francisco.
Disclosure: Ratziu reports financial connections with Galmed, Genfit, Gilead, Intercept and Novartis.