A3 adenosine receptor agonist safe, effective for treating NAFLD

Namodenoson, an A3 adenosine receptor (A3AR) agonist, shows clinical activity against nonalcoholic fatty liver disease (NAFLD) with or without nonalcoholic steatohepatitis (NASH), according to data from a phase II study.

This study randomized 60 patients with NAFLD (alanine aminotransferase [ALT] ≥60 IU/L) to receive oral namodenoson 12.5 mg (n=21) or 25 mg (n=19) or placebo (n=20), administered twice daily for 12 weeks. The total follow-up was 16 weeks.

The primary efficacy endpoint of serum ALT decreased over time in a dose-dependent manner in the namodenoson groups. The change from baseline (CFB) in ALT with the 25-mg namodenoson regimen at 12 weeks trended towards significance relative to placebo (p=0.066).

Likewise, there was a dose-dependent decrease in serum aspartate aminotransferase (AST) levels in the namodenoson group. Compared with placebo, the 25-mg regimen produced a clinically meaningful change in AST from baseline to 12 weeks (p=0.03).

At week 12, ALT normalized in 31.6 percent of the patients in the namodenoson 25-mg arm and in 20.0 percent in the placebo arm (p=0.405). At week 16, the proportion of patients who achieved this outcome increased to 36.8 percent in the former and decreased to 10.0 percent in the latter (p=0.038).

A3AR expression levels were stable over time across the three treatment arms. Namodenoson at either dose was well tolerated, with no drug-emergent severe adverse events (AEs), drug-drug interactions, hepatotoxicity, or deaths.

There were three AEs deemed possibly related to study treatment, namely myalgia (12.5 mg), muscular weakness (25 mg), and headache (25 mg).