Novel thyroid hormone receptor β agonist shows promise in MASH

Treatment with the thyroid hormone receptor β (THR-β) agonist ALG-055009 appears to yield substantial reductions in liver fat with no relevant safety issues in patients with metabolic dysfunction-associated steatohepatitis (MASH), according to a phase IIa study.

The study included 102 adults (mean age 50.2 years, 62 percent female, 86 percent White) with a BMI of ≥25 kg/m² and a diagnosis of presumed nonalcoholic steatohepatitis or MASH with F1–F3 liver fibrosis. These participants were randomly assigned to receive ALG-055009 at 0.3 mg (n=20), 0.5 mg (n=22), 0.7 mg (n=20), or 0.9 mg (n=18) or placebo (n=22). Treatment was administered orally, once daily for 12 weeks. Only participants with bodyweight >85 kg were allocated to the 0.9-mg ALG-055009 group.

The primary endpoint was percentage change in liver fat, assessed using MRI-proton density fat fraction (MRI-PDFF), at week 12. Two participants in the 0.3-mg group, one in the 0.5-mg group, one in the 0.9-mg group, and one in the placebo group did not have baseline and week 12 MRI-PDFF data and were thus excluded in the analysis of the primary endpoint.

At week 12, the mean relative change in liver fat was –6.9 percent with 0.3-mg ALG-055009, –11.2 percent with 0.5 mg, –25.9 percent with 0.7 mg, and –24.3 percent with 0.9 mg vs 7.3 percent with placebo. Placebo-adjusted changes in liver fat were significant in the 0.5-mg group (–18.5 percent; p=0.014), 0.7-mg group (–33.2 percent; p<0.0001), and 0.9-mg group (–31.6 percent; p=0.0001).

In terms of safety, treatment-emergent adverse events (TEAEs) occurred in 65 percent of participants in the 0.3-mg ALG-055009 group, 45 percent in the 0.5-mg group, 65 percent in the 0.7-mg group, 61 percent in the 0.9-mg group, and 73 percent in the placebo group. Most TEAEs were mild or moderate, with the most common being diarrhoea and constipation.

Gastrointestinal TEAE rates were similar between the ALG-055009 and placebo groups. There were no clinically meaningful changes seen in laboratory tests, electrocardiogram, vital signs, physical exams, or thyroid function.

Only one participant experienced a serious adverse event, and this was in the placebo group. There were no deaths documented during the study.