Dong-A ST(170900) and its affiliate MetaVia are accelerating development of a next-generation metabolic-dysfunction–associated steatohepatitis (MASH) therapy. With market competition intensifying after the launch of the world's first MASH treatment, they aim to target both monotherapy and combination-therapy markets with a new drug candidate.
MASH is a progressive liver disease closely linked to metabolic disorders such as obesity, type 2 diabetes, and dyslipidemia. It often shows no specific symptoms early on, but as liver fibrosis advances, it can lead to cirrhosis and liver cancer. The number of patients is rising quickly, but treatment options are limited.
Market competition is also heating up quickly. With the 2024 launch of the world's first MASH therapy, "resmetirom (Resmetirom)," development of next-generation treatments and combination regimens has gained momentum. Because MASH involves a complex interplay of fat accumulation, inflammation, fibrosis, and metabolic dysfunction, treatment strategies that combine multiple mechanisms rather than relying on a single one are drawing attention.
MetaVia's "Vanoglipel (Vanoglipel)," now in development, is an oral new drug candidate based on the GPR119 mechanism of action. GPR119 is present not only in the gut and pancreas but also in hepatocytes, macrophages, and hepatic stellate cells involved in MASH pathophysiology. Vanoglipel directly targets GPR119 on these cells to simultaneously suppress intrahepatic fat accumulation, inflammation, and fibrosis progression.
In a prior U.S. phase 2a study, the drug showed reductions in alanine aminotransferase (ALT), a liver injury marker, along with potential improvements in liver fat content and liver stiffness. Glycated hemoglobin (HbA1c), an index of glycemic control, also improved. Given that many MASH patients have coexisting obesity and diabetes, the candidate is seen as competitive.
MetaVia recently presented combination data with resmetirom at the American Diabetes Association (ADA 2026). In a MASH mouse model, coadministration of the two drugs reduced body weight by 23.6% versus control, while fat mass and epididymal fat decreased by 43.5% and 42.1%, respectively. ALT fell by 83.5%, and tissue analyses confirmed improvements in biomarkers related to hepatic fat accumulation, inflammation, and fibrosis.
Because the two drugs act through different mechanisms, using them together may yield greater therapeutic effects. Resmetirom focuses on reducing liver fat accumulation, while Vanoglipel helps improve blood glucose, body weight, and liver metabolism. The company analyzed that combining the two could increase energy expenditure and further enhance weight loss.
MetaVia also confirmed effects when coadministered with the diabetes drug metformin. According to results presented at the American Diabetes Association (ADA 2026), the combination group outperformed the Vanoglipel monotherapy group in glycemic control and weight loss.
Nonfasting blood glucose fell by 28.7%, and body weight decreased by 16.3% versus control. Fat mass also declined, while levels of glucagon-like peptide (GLP-1) and peptide YY (PYY)—hormones involved in glycemic control and appetite suppression—increased 6.4-fold and 1.5-fold, respectively.
The findings suggest Vanoglipel could extend its reach beyond MASH to type 2 diabetes. Attention is on whether it can secure competitiveness in both the monotherapy and combination-therapy markets going forward.