Aligos Therapeutics has reported positive topline results from the Phase IIa HERALD clinical trial of ALG-055009, a thyroid hormone receptor beta agonist, for the treatment of metabolic-dysfunction-associated steatohepatitis (MASH). The data indicates significant reductions in liver fat content and improvements in atherogenic lipid profiles, suggesting a potential new therapeutic avenue for MASH patients.
The double-blind, randomized, placebo-controlled study enrolled 102 subjects with presumed MASH and stage I-III liver fibrosis. Participants were administered one of four doses of ALG-055009 or a placebo once daily for 12 weeks. The primary endpoint focused on the relative change in liver fat content at week 12, assessed alongside safety, pharmacokinetics (PK), and non-invasive biomarkers.
Significant Liver Fat Reduction
The trial results demonstrated that doses ranging from 0.5mg to 0.9mg of ALG-055009 led to significant median relative reductions in liver fat. Up to 70% of subjects experienced a ≥30% relative decrease from baseline. These findings suggest a robust treatment effect of ALG-055009 on liver steatosis, a key pathological feature of MASH.
Tolerability and Safety Profile
ALG-055009 exhibited a favorable tolerability profile, with no serious adverse events or signs of clinical hyper/hypothyroidism reported. Most treatment-emergent adverse events were mild to moderate, and the incidence of gastrointestinal-related adverse events was similar to the placebo group. This safety profile is crucial for a chronic therapy targeting a prevalent condition like MASH.
Impact on Atherogenic Lipids
Beyond liver fat reduction, treatment with ALG-055009 resulted in significant decreases in atherogenic lipids, including LDL-C, lipoprotein (a), and apolipoprotein B. These improvements in lipid profiles could potentially reduce cardiovascular risk, a common comorbidity in MASH patients.
Future Directions
Aligos Therapeutics is currently in early discussions with potential partners to fund the continued development of ALG-055009. The company plans to complete the activities required for a Phase IIb study by the middle of 2025 and is assessing potential Phase IIb clinical trial designs. These next steps will be crucial in further evaluating the efficacy and safety of ALG-055009 in a larger patient population.
Lawrence Blatt, chairman, president, and CEO of Aligos Therapeutics, stated, "The data demonstrates that these enhanced pharmacologic properties did indeed translate into robust improvements in liver fat reduction." This positive outcome underscores the potential of ALG-055009 as a promising therapeutic option for MASH.
