According to a phase I/II trial, short-term administration of ARO-HSD exhibited good tolerability  at doses ≤200 mg and decreased hepatic HSD17β13 mRNA and protein expression, which was followed by a decline in alanine aminotransferase (ALT). Researchers sought to assess the benefits of ARO-HSD in individuals having verified or clinically suspected non-alcoholic steatohepatitis (NASH) as well as in normal healthy volunteers.

In this proof-of-concept study, there were a total of 32 normal healthy volunteers and 18 NASH sufferers. On the first day, the double-blind normal healthy volunteers were subcutaneously given single increasing dosages of ARO-HSD (25, 50, 100, or 200 mg) or placebo. ARO-HSD (25, 100, or 200 mg) was administered subcutaneously to open-label patient cohorts on days one and twenty-nine. In order to assess the expression levels of HSD17β13 mRNA and protein, liver biopsies were done on patients prior to the dosage and on Day 71.

With no major adverse events or medication discontinuations, ARO-HSD therapy was well tolerated. Mild, transient injection site responses were the most often reported treatment-emergent adverse events. From baseline to Day 71, the mean alterations in liver HSD17β13 mRNA were -56.9% (25 mg), -85.5% (100 mg), and -93.4% (200 mg). HSD17β13 mRNA decrease across all pooled subjects was 78.6%.

Across dosages, there was a similar decline in hepatic HSD17β13 protein levels. In individuals, alanine aminotransferase (ALT) mean alterations from baseline to Day 71 were -7.7% (25 mg), -39.3% (100 mg), and -42.3% (200 mg). Therefore, ARO-HSD, an RNA interference therapeutic designed to selectively minimize HSD17β13 mRNA expression in hepatocytes, seems to be promising for NASH management.