MetaVia Inc. (Nasdaq: MTVA) has announced positive top-line results from its Phase 2a clinical trial of DA-1241 in patients with presumed metabolic dysfunction-associated steatohepatitis (MASH). The 16-week trial, which included a part exploring DA-1241 as a monotherapy and another investigating its efficacy in combination with sitagliptin, demonstrated statistically significant improvements in key markers of liver health and glucose control.
Key Findings from the Phase 2a Trial
The Phase 2a trial of DA-1241, a novel G-Protein-Coupled Receptor 119 (GPR119) agonist, involved 109 patients randomized into different treatment groups. The primary endpoint was the change from baseline in alanine transaminase (ALT) levels at Week 16.
- ALT Reduction: DA-1241 (100mg) showed statistically significant reductions in ALT levels at weeks 4 and 8 (p=0.0159 and p=0.0342, respectively), with a near statistically significant reduction at week 16 (p=0.0506) compared to placebo.
- ALT Normalization: DA-1241 50mg demonstrated a statistically significant improvement in the normalization of ALT levels compared to placebo, with an odds ratio of 10.500 (p=0.0487).
- CAP Score Improvement: Both DA-1241 100mg and DA-1241 100mg + Sitagliptin 100mg showed significant improvements in the CAP score compared to placebo (p=0.0308 and p=0.0452, respectively).
- FAST Score Reduction: DA-1241 100mg + Sitagliptin 100mg showed a statistically significant reduction in the FAST score compared to placebo (p=0.0416).
- HbA1c Reduction: DA-1241 100mg and DA-1241 100mg + Sitagliptin 100mg showed significant reductions in HbA1c from baseline at Week 16 compared to the placebo group (p=0.0179 and p=0.0050, respectively).
Safety and Tolerability
DA-1241 was reported to be well-tolerated, with most adverse events being mild and no drug-related serious adverse events (SAEs) reported in the treatment groups.
Mechanism of Action and Future Development
DA-1241 is a GPR119 agonist that promotes the release of key gut peptides GLP-1, GIP, and PYY, which play a role in glucose and lipid metabolism. MetaVia is also conducting pre-clinical studies to explore other combination therapies for DA-1241. The company anticipates an end-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) in the first half of 2025.
Expert Commentary
"Achieving the primary endpoint of a reduction in ALT levels through direct hepatic effects, as well as notable secondary endpoints, including significantly lower HbA1C levels compared to the placebo, are extremely positive results for DA-1241, especially given the small study size," stated Hyung Heon Kim, President and Chief Executive Officer of MetaVia.
About MASH
Metabolic Dysfunction-Associated Steatohepatitis (MASH) is a progressive liver disease characterized by inflammation and liver damage due to fat accumulation in the liver. It is often associated with metabolic risk factors such as obesity, type 2 diabetes, and high blood pressure. There is a significant unmet need for effective and safe treatments for MASH.
