This phase 2a RCT (HERALD, NCT06342947) evaluated four oral doses of ALG-055009 (0.3, 0.5, 0.7, or 0.9 mg once daily) vs. placebo over 12 weeks in 102 non-cirrhotic adults (aged 18–75, BMI ≥25 kg/m²) with presumed MASH and F1–F3 liver fibrosis, measuring hepatic fat reduction by MRI-PDFF as the primary endpoint.
The 0.7 mg and 0.9 mg doses produced statistically significant, placebo-adjusted reductions in liver fat at 12 weeks: −33.2% (95% CI −48.1 to −18.3; p<0.0001) and −31.6% (95% CI −47.4 to −15.8; p=0.0001), respectively. Treatment-emergent adverse events were similar to placebo (45–65% on drug vs. 73% placebo), mostly mild/moderate GI events, with no deaths and no clinically meaningful changes in thyroid function.
- Short 12-week duration with only MRI-PDFF as the endpoint; no histologic outcomes assessed. - Diagnosis of MASH was presumed (not biopsy-confirmed at enrollment), limiting certainty about baseline disease severity. - Small per-group sample sizes (n=18–22) reduce precision and generalizability.
ALG-055009 at 0.7–0.9 mg daily cut liver fat by roughly one-third vs. placebo over 12 weeks with a safety profile comparable to placebo — a notable early signal for this THR-β agonist. Longer trials with histologic endpoints are needed before clinical adoption.
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