Aligos' MASH Drug Cuts Liver Fat in Phase 2, Stock Falls

Aligos Therapeutics has achieved notable progress in the treatment of metabolic-dysfunction associated steatohepatitis (MASH) through a midstage clinical trial. The company reported that its drug candidate, ALG-055009, demonstrated significant reductions in liver fat over a 12-week period across three different doses. However, these promising results have not yet inspired confidence among investors.

The drug, an oral thyroid hormone receptor beta agonist, was tested in a phase 2a study named HERALD, involving 102 patients with presumed MASH and stage 1 to 3 liver fibrosis. The study's primary endpoint was to measure the percentage of relative change in liver fat from baseline at 12 weeks using a Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) scale, along with additional noninvasive biomarkers.

Participants in the trial were randomized into one of four dosing groups (0.3, 0.5, 0.7, or 0.9 mg) or a placebo group, with dosing occurring once daily for 12 weeks. The 0.9 mg dose was only administered to patients weighing more than 85 kg (approximately 187 pounds), while no weight restrictions were applied to the other groups. This stratification aimed to account for the diverse body weights among MASH patients, according to Aligos President and CEO Lawrence Blatt, Ph.D.

The results showed that the 0.5 mg, 0.7 mg, and 0.9 mg doses achieved statistically significant reductions in liver fat, with the 0.7 mg dose showing the highest placebo-adjusted median relative reduction at 46.2%. The lowest dose, 0.3 mg, did not achieve statistical significance. Up to 70% of patients receiving ALG-055009 experienced a relative reduction in liver fat of 30% or more compared to baseline.

MASH is a severe form of fatty liver disease that can progress to scarring, cancer, or liver failure. Despite the promising data, Aligos' stock experienced a decline, dropping about 20% after the announcement.

Blatt emphasized that the current data is preliminary, covering safety and primary efficacy metrics as well as a subset of biomarkers up to Week 12. Additional biomarkers and follow-up safety data are to be evaluated in the coming weeks. Importantly, the drug was well tolerated, with no serious adverse events or dose reductions. Most adverse events were mild to moderate, and the incidence of gastrointestinal-related issues was similar to that of the placebo group.

ALG-055009 was also associated with significantly lower levels of atherogenic lipids such as LDL-C, lipoprotein (a), and apolipoprotein B. This positions ALG-055009 favorably against other MASH treatments, like Madrigal Pharmaceuticals' resmetirom, which recently received accelerated FDA approval. Although no head-to-head comparison was conducted, Aligos claims a higher placebo-adjusted median liver fat reduction for ALG-055009 compared to resmetirom.

Another competitor in the space, Viking Therapeutics, has also shared positive phase 2b results for its MASH candidate, a thyroid hormone beta receptor agonist, showing up to 51.7% median relative reduction in liver fat.

Aligos is now planning further clinical development, aiming to start a phase 2b study by mid-2025. The company is exploring potential partnerships and other funding options to support the next phase of development. Blatt indicated that while a partnership would be welcome, it would need to provide fair financial compensation for the value created by the drug. Otherwise, the company would seek alternative funding routes.

MASH has proven to be a challenging condition for drug development, with many companies failing to achieve the necessary safety and efficacy in trials. The chronic liver disease is projected to affect approximately 27 million Americans by 2030, up from 16.5 million in 2015.