ALG-055009 in non-cirrhotic adults with metabolic dysfunction-associated steatohepatitis (HERALD): a randomised, double-blind, placebo-controlled, phase 2a trial.
Rohit Loomba, Stanley Wang, Dimple Desai et al.
✦ AI-curated · Sources linked
In 30 seconds
The HERALD study was a randomised, double-blind, placebo-controlled phase 2a trial of once-daily ALG-055009 in non-cirrhotic adults with presumed MASH and F1–F3 fibrosis. Among 102 participants assigned to four dose groups or placebo, the primary outcome was relative change in liver fat measured by MRI-PDFF after 12 weeks. Placebo-adjusted changes were -18·5% with 0·5 mg, -33·2% with 0·7 mg, and -31·6% with 0·9 mg; these reductions were statistically significant. Adverse-event rates were broadly similar across groups, and most events were mild or moderate.
Key findings
- At 12 weeks, placebo-adjusted relative liver-fat change was -33·2% (95% CI -48·1 to -18·3; p<0·0001) with 0·7 mg ALG-055009.
- Placebo-adjusted liver-fat changes were -18·5% (-33·3 to -3·8; p=0·014) with 0·5 mg and -31·6% (-47·4 to -15·8; p=0·0001) with 0·9 mg.
- Treatment-emergent adverse events occurred in 45–65% of ALG-055009 recipients and 73% of placebo recipients; most were mild or moderate.
Why it matters
Liver-fat reduction is a relevant signal in MASH drug development, and this trial found significant reductions at three ALG-055009 doses over 12 weeks. The findings provide early evidence to inform further evaluation of this THR-β agonist, while the short-term imaging outcome does not establish improvement in liver histology or longer-term clinical outcomes.
What to keep in mind
The trial lasted 12 weeks and assessed liver fat by MRI-PDFF; it does not establish effects on liver histology or longer-term outcomes.