Aldafermin reduces liver fat, improves fibrosis in NASH

Aldafermin decreased liver fat and trended toward fibrosis improvement among patients with non-alcoholic steatohepatitis, according to a study published in Gastroenterology.

“Finally, this is the first report to date evaluating the longitudinal change in NASH histology in response to a therapeutic agent in 24 weeks, the shortest time period for a placebo-controlled trial thus far,” Stephen A. Harrison, MD, from the Radcliffe department of medicine at the University of Oxford and colleagues wrote. “The speed and magnitude at which such histological change can happen indicate that fibrosis and NASH may be more plastic and malleable than previously thought.”

Harrison and colleagues performed a double-blind study of 78 patients with NASH. They assigned patients to either subcutaneous placebo (n = 25) or aldafermin 1 mg (n = 53) daily for 24 weeks. The change in absolute liver fat content from baseline to week 24 served as the primary outcome. Other outcomes of concern were serum markers and histological measures of fibrosis improvement and NASH resolution.

Results showed the aldafermin group had a greater decrease in absolute liver fat content (7.7%) compared with placebo (2.7%) at week 24 (difference, reduction of 5%; 95% CI, reduction of 81.9).

“Aldafermin produced significantly greater decreases in levels of 7 alpha-hydroxy-4-cholesten-3-one, bile acids, alanine and aspartate aminotransferases, and Pro-C3 than placebo,” the researchers wrote.

Investigators reported that 38% of patients who received aldafermin had fibrosis improvement with no worsening of NASH vs. 18% of patients who received placebo (P = .1). Further, 24% of patients in the aldafermin group, vs. 9% in the placebo group, experienced NASH resolution with no worsening of fibrosis (P = .2). Discontinuations due to adverse events occurred in 4% of the placebo group while there were none in the aldafermin group.