MetaVia's Vanoglipel Shows Dual Benefits in MASH Phase 2a Trial with Significant HbA1c Reduction and Liver Improvements
核心洞察
MetaVia (搜索)'s vanoglipel (搜索) (DA-1241), a GPR119 (搜索) agonist, demonstrated clinically meaningful HbA1c reductions of 0.54% with monotherapy and 0.66% with combination therapy in a 16-week Phase 2a trial for MASH (搜索) patients.
The oral therapy showed dual hepatic and metabolic benefits, significantly reducing plasma ALT levels, improving liver steatosis and fibrosis, while also reducing inflammatory biomarkers and pathogenic lipids.
The randomized, placebo-controlled study enrolled 109 patients with presumed MASH (搜索), with vanoglipel (搜索) showing good tolerability and no treatment-emergent adverse events leading to discontinuation.
MetaVia (搜索) Inc. announced positive results from its Phase 2a clinical trial evaluating vanoglipel (搜索) (DA-1241), a potent and selective G protein-coupled receptor 119 (搜索) (GPR119 (搜索)) agonist, for the treatment of metabolic dysfunction-associated steatohepatitis (搜索) (MASH (搜索)). The data, presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025 in Washington D.C., demonstrate the drug's differentiated dual activity across both hepatic and metabolic pathways.
Trial Design and Patient Population
The Phase 2a randomized, placebo-controlled trial enrolled 109 subjects with presumed MASH (搜索) and qualifying baseline alanine transaminase (ALT) and imaging analyses. Patients were randomized in a 2:1:2:2 ratio to receive placebo, vanoglipel (搜索) 50 mg, vanoglipel 100 mg alone, or vanoglipel 100 mg with a DPP4 (搜索) inhibitor once daily for 16 weeks.
The study evaluated vanoglipel (搜索) both as monotherapy and in combination with a dipeptidyl peptidase-4 inhibitor (DPP4i) to augment endogenous GLP-1 (搜索) action. GPR119 (搜索) agonists directly stimulate GLP-1 secretion, thereby increasing total GLP-1 levels, and when combined with a DPP4 (搜索) inhibitor, the treatment can extend the action of both basal endogenous GLP-1 and the secreted GLP-1 induced by GPR119 activation.
Glycemic Control Improvements
Vanoglipel (搜索) demonstrated rapid and sustained improvements in glycemic control, with reductions in glycated hemoglobin (HbA1c) observed from the fourth week of treatment. At Week 16, mean HbA1c decreased by −0.54%p with vanoglipel monotherapy and −0.66%p with combination therapy, reflecting enhanced incretin action.
Patients treated with vanoglipel (搜索) showed clinically meaningful HbA1c reductions of 0.37%p, 0.41%p, and 0.54%p at weeks 4, 8, and 16, respectively, from a baseline of 6.99%, despite nearly half of participants being non-diabetic (p ≤ 0.05 vs. placebo). These findings highlight vanoglipel's ability to improve glucose control independently of weight loss, suggesting its mechanism is differentiated from other metabolic liver disease therapies.
Hepatic Benefits and Biomarker Improvements
In addition to its glycemic effects, vanoglipel (搜索) significantly decreased plasma ALT levels in subjects with baseline ALT between 40 and 200 U/L. The reduction in ALT was not further enhanced by co-administration with a DPP4 (搜索) inhibitor, suggesting that vanoglipel monotherapy drives the majority of the observed hepatoprotective effects.
Vanoglipel (搜索) improved liver steatosis as measured by controlled attenuation parameter (CAP) and reduced liver stiffness by vibration-controlled transient elastography (VCTE). Non-invasive assessments, including FAST and NIS-4 scores, also improved from baseline, reinforcing vanoglipel's potential to address both hepatic and metabolic components of MASH (搜索).
The treatment reduced circulating biomarkers associated with cell death (CK18F/M30), inflammation (hs-CRP, CCL2), and fibrosis (TIMP1), consistent with its proposed hepatoprotective mechanism. Additionally, vanoglipel (搜索) 100 mg reduced pathogenic lipids in plasma lipidomic profiles, including glycerolipids (DG36:4, TG52:4) and glycerophospholipids (PE38:4, PE38:5), suggesting favorable remodeling of lipid metabolism.
Safety Profile
Vanoglipel (搜索) was well tolerated across all treatment groups, with no treatment-emergent adverse events leading to discontinuation, except for one in the placebo group.
Clinical Significance and Future Development
"The encouraging additional Phase 2a results, presented at AASLD, highlight vanoglipel (搜索)'s differentiated mechanism and its potential to target both hepatic and metabolic drivers of MASH (搜索) in a single oral therapy," stated Hyung Heon Kim, President and Chief Executive Officer of MetaVia (搜索). "In addition to improvements in liver inflammation, fibrosis, and steatosis, vanoglipel demonstrated meaningful reductions in HbA1c among patients with type 2 diabetes (搜索) and prediabetes, as well as favorable shifts in plasma lipidomic profiles, reducing disease-associated glycerolipids and glycerophospholipids linked to hepatic injury."
Kim added that the data reinforce vanoglipel (搜索)'s potential to address the complex interplay between metabolic dysfunction and liver disease, with consistent biochemical, imaging, and metabolic improvements supporting its continued development as both a monotherapy and combination therapy for MASH (搜索) and related metabolic disorders.
About Vanoglipel
Vanoglipel (搜索) (DA-1241) is a novel G-Protein-Coupled Receptor 119 (GPR119 (搜索)) agonist with development optionality as a standalone and/or combination therapy for both MASH (搜索) and type 2 diabetes (搜索). Agonism of GPR119 in the gut promotes the release of key gut peptides GLP-1 (搜索), GIP, and PYY, which play roles in glucose metabolism, lipid metabolism and weight loss. The therapeutic potential of vanoglipel has been demonstrated in multiple pre-clinical animal models of MASH and type 2 diabetes, where it reduced hepatic steatosis, inflammation, fibrosis, and improved glucose control.