Dong-A ST and MetaVia announced on June 23rd that they presented their preclinical research on the combination therapy of ‘DA-1241’ and the FGF21 analog ‘Efruxifermin’ at ADA 2025, the American Diabetes Association’s annual conference held in Chicago from June 20th to 23rd.
DA-1241 is a first-in-class oral synthetic drug that operates through GPR119 activation. Animal studies have demonstrated its effectiveness in improving blood glucose and lipid profiles, as well as directly acting on the liver to reduce inflammation and fibrosis. The company completed a Phase 2a clinical trial targeting suspected MASH patients in December of last year.
The study evaluated the efficacy of a 12-week treatment course in a mouse model of MASH, comparing the effects of combined DA-1241 and Efruxifermin therapy, each as monotherapies, and a control group. DA-1241 was administered orally once daily, while Efruxifermin was given via subcutaneous injection once weekly.
Results showed that approximately 94% of animals receiving the combination therapy experienced a reduction of more than 2 points in the NAFLD Activity Score (NAS), a marker of fatty liver disease activity, compared to baseline. The combination group also exhibited a significant reduction in liver fibrosis area, with some animals showing a decrease in fibrosis stage.
During the 12-week treatment, DA-1241 did not significantly affect body weight, unlike Efruxifermin, which caused about a 17% weight loss. Importantly, the combination therapy resulted in greater reductions in plasma ALT levels and liver lipids without additional weight loss.
Furthermore, the combined therapy significantly improved the expression of liver genes involved in inflammation and fibrosis, as well as decreased levels of blood glucose and inflammatory indicators.
Previous results from the global Phase 2 clinical trial of DA-1241 also confirmed its liver-protective effects, showing improvements in ALT (a liver damage marker), CAP (a fatty liver index), MRI-PDFF (liver fat content), NIS-4 (a risk score for liver disease), and FAST (a non-invasive fibrosis assessment).
Efruxifermin, a recombinant protein designed to mimic liver-secreted hormone FGF21, possesses anti-inflammatory, blood glucose-lowering, weight-reduction, and lipid metabolism-regulating effects. The drug is currently in global trials targeting MASH, obesity, and type 2 diabetes.
A spokesperson from Dong-A ST commented, “We are conducting various combination trials aimed at developing differentiated MASH treatments, and this study confirms that the combination of DA-1241 and Efruxifermin is more effective for MASH therapy. We will continue with follow-up and diverse combination trials to develop a leading treatment in the global MASH market.”
The American Diabetes Association (ADA) is the world’s most prestigious conference for presenting cutting-edge research on diabetes, obesity, MASH, and other metabolic diseases. This year’s event was held in Chicago from June 20th to 23rd.
