Nonalcoholic steatohepatitis (NASH), a chronic liver disease without an approved 
therapy, is associated with lipotoxicity and insulin resistance and is a major 
cause of cirrhosis and hepatocellular carcinoma. Aramchol, a partial inhibitor 
of hepatic stearoyl-CoA desaturase (SCD1) improved steatohepatitis and fibrosis 
in rodents and reduced steatosis in an early clinical trial. ARREST, a 52-week, 
double-blind, placebo-controlled, phase 2b trial randomized 247 patients with 
NASH (n = 101, n = 98 and n = 48 in the Aramchol 400 mg, 600 mg and placebo 
arms, respectively; NCT02279524 ). The primary end point was a decrease in 
hepatic triglycerides by magnetic resonance spectroscopy at 52 weeks with a dose 
of 600 mg of Aramchol. Key secondary end points included liver histology and 
alanine aminotransferase (ALT). Aramchol 600 mg produced a placebo-corrected 
decrease in liver triglycerides without meeting the prespecified significance 
(-3.1, 95% confidence interval (CI) -6.4 to 0.2, P = 0.066), precluding further 
formal statistical analysis. NASH resolution without worsening fibrosis was 
achieved in 16.7% (13 out of 78) of Aramchol 600 mg versus 5% (2 out of 40) of 
the placebo arm (odds ratio (OR) = 4.74, 95% CI = 0.99 to 22.7) and fibrosis 
improvement by ≥1 stage without worsening NASH in 29.5% versus 17.5% (OR = 1.88, 
95% CI = 0.7 to 5.0), respectively. The placebo-corrected decrease in ALT for 
600 mg was -29.1 IU l-1 (95% CI = -41.6 to -16.5). Early termination due to 
adverse events (AEs) was <5%, and Aramchol 600 and 400 mg were safe, well 
tolerated and without imbalance in serious or severe AEs between arms. Although 
the primary end point of a reduction in liver fat did not meet the prespecified 
significance level with Aramchol 600 mg, the observed safety and changes in 
liver histology and enzymes provide a rationale for SCD1 modulation as a 
promising therapy for NASH and fibrosis and are being evaluated in an ongoing 
phase 3 program.