Efficacy and Safety of HSK31679 in Asian Patients With MASLD: A Randomized Controlled Trial

This study evaluated the efficacy and safety of the thyroid hormone receptor β agonist HSK31679 in Asian patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This was a phase 2a, multicenter, randomized, double-blind, placebo-controlled study at 26 centers in China. Subjects with a liver fat content (LFC) of ≥ 8% at screening, when assessed by magnetic resonance imaging-proton density fat fraction, were eligible. Subjects were randomly assigned in a 1:1:1:1:1 ratio using a centralized randomization system to receive daily oral HSK31679 40mg, 80mg, 160mg, ezetimibe 10mg, or placebo. The primary endpoint was a relative change from baseline in LFC (%) after 12 weeks of treatment. 210 participants were randomly assigned to placebo (n=42), HSK31679 40 mg (n=42), HSK31679 80 mg (n=42), HSK31679 160 mg (n=42) or ezetimibe (n=42). At week 12, the mean relative change from baseline in LFC was -4.1% in the placebo group, -14.0% in the 40 mg group (mean difference versus placebo -9.9% [95% CI -21.5% to 1.6%], P = 0.092), -22.7% in the 80 mg group (-18.6% [-30.2% to -7.0%], P = 0.002), and -29.2% in the 160 mg group (-25.2% [-36.8% to -13.5%], P < 0.001). The most common treatment-emergent adverse event was diarrhea (11 [26.2%] of patients in the 40 mg group, 13 [31.0%] in the 80 mg group, 16 [38.1%] in the 160 mg group, and 2 [4.8%] in the placebo group). Non-drug-related serious adverse events or grade 3 adverse events were reported. In Asian MASLD patients, HSK31679 was well tolerated, with significant reductions in LFC after 12 weeks of treatment with 80 mg and 160 mg. NCT05795517.