Icosabutate shows potential as treatment for MASH

Treatment with icosabutate is associated with encouraging fibrosis and noninvasive biomarker data, lending support for its development in patients with metabolic dysfunction-associated steatohepatitis (MASH), reports a study.

A phase IIb, multicentre, randomized, placebo-controlled trial was conducted for 52 weeks to examine the efficacy of icosabutate in patients with MASH and F1–F3 (mild to severe) fibrosis. Participants were randomly allocated to receive once-daily, oral icosabutate 300 mg, 600 mg, or placebo.

The proportion of patients with MASH resolution with no worsening of fibrosis in the 600-mg arm was the primary efficacy endpoint.

A total of 187 patients were included in the primary population for efficacy analysis. Of these, 62 received placebo, 58 received icosabutate 300 mg, and 67 received icosabutate 600 mg.

The primary endpoint was not met. The proportion of patients with MASH resolution favoured the 600-mg arm, but this did not reach statistical significance (23.9 percent vs 14.5 percent; odds ratio [OR], 2.01, 95 percent confidence interval [CI], 0.8–5.08; p=0.13).

More patients on icosabutate were able to achieve a ≥1-stage improvement in fibrosis, with a response rate of 29.3 percent in the 300-mg arm (OR, 2.89, 95 percent CI, 1.09–7.70) and 23.9 percent in the 600-mg arm (OR, 2.4, 95 percent CI, 0.90–6.37) vs 11.3 percent in the placebo arm.

"An improvement in fibrosis was observed using AI-assisted digital pathology,” the investigators said. “Marked decreases in biomarkers of liver damage were observed.” 

Additionally, the use of icosabutate was safe and well tolerated. Treatment-emergent adverse events were generally mild or moderate in severity, and no drug-induced liver injury were reported.