Simedeutirom shows promise in Asians with MASH

In the treatment of Chinese patients with metabolic dysfunction-associated steatohepatitis (MASH) and F2 or F3 fibrosis, the use of the selective thyroid hormone receptor-β agonist simedeutirom helps improve disease activity without worsening of fibrosis, as shown in a phase IIb trial.

The trial was conducted at 42 sites across China and included 179 adult patients (median age 42 years, 65 percent male) with biopsy-confirmed MASH, a nonalcoholic fatty liver disease activity score (NAS) of ≥4, F2 or F3 fibrosis, and MRI-proton density fat fraction liver fat content of ≥8 percent.

The patients were randomly assigned to receive simedeutirom at 80 mg (n=59) or 160 mg (n=60) or placebo (n=60). Treatment was administered once daily for 52 weeks.

The primary endpoint was MASH improvement, defined as a ≥2-point reduction in NAS, ≥1-point improvement in hepatocellular ballooning, and no increase in steatosis score, without worsening of fibrosis (ie, no increase in fibrosis stage) at week 52.

At week 52, MASH improvement occurred in 37 percent of patients in the simedeutirom 80-mg group and 30 percent in the 160-mg group vs 10 percent in the placebo group. Treatment with simedeutirom was associated with around fivefold greater odds of achieving MASH improvement compared with placebo (8 mg: odds ratio [OR], 4.87, 95 percent confidence interval [CI], 1.76–13.48; p=0.0023; 160 mg: OR, 5.24, 95 percent CI, 1.74–15.72; p=0.0032).

In terms of safety, grade 3 treatment-emergent adverse events (TEAEs) occurred in 5 percent of patients in the simedeutirom 80-mg group, 8 percent in the 160-mg group, and 5 percent in the placebo group. Serious AEs occurred 5 percent, 6 percent, and 5 percent of patients in the respective groups, and none of these events were related to treatment. There were no reports of grade 4–5 TEAEs, deaths, or AEs leading to treatment discontinuation.