MetaVia Announces Interim Data From Part 3B Of Its Phase 1 Clinical Trial Of DA-1726 Targeting Both GLP-1 And Glucagon Receptors; Results Demonstrate 68% Placebo-Adjusted Reduction In Liver Fat And 13.5% Placebo-Adjusted Body Weight Reduction Following 16 Weeks Of Once-Weekly DA-1726 Treatment In Otherwise Healthy Adults With Obesity; Plans Phase 2 For H2 2027
Benzinga Newsdesk 20 minutes ago
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At Day 109, 10 of 12 DA-1726-treated participants (83%) in the MRI substudy achieved a relative liver fat reduction of at least 30%, compared with none on placebo. All DA-1726-treated participants with baseline liver
At Day 109, 10 of 12 DA-1726-treated participants (83%) in the MRI substudy achieved a relative liver fat reduction of at least 30%, compared with none on placebo. All DA-1726-treated participants with baseline liver steatosis achieved MRI-PDFF below 5%. DA-1726 also lowered HbA1c from 5.79% at baseline to 5.33% at Day 109, a 0.24 percentage-point placebo-adjusted reduction in participants who were not diabetic at entry, with significant reductions in adipose tissue and relative preservation of lean tissue and muscle volume.
"These are the most compelling clinical data we have generated to date supporting DA-1726's potential as a liver-focused cardiometabolic therapy," said Hyung Heon Kim, President and Chief Executive Officer of MetaVia. "A 68% placebo-adjusted reduction in liver fat after approximately 16 weeks, together with all five participants who entered the study with liver steatosis achieving MRI-PDFF below 5%, provides a strong clinical rationale for expanding DA-1726 into liver disease. Importantly, these liver findings were accompanied by 13.5% placebo-adjusted weight loss, improvements in HbA1c, and significant reductions across visceral and subcutaneous adipose tissue, while lean tissue and muscle volume were relatively preserved."
Mr. Kim continued, "The next step for DA-1726 is clear. We intend to build on these results by advancing the program into both metabolic dysfunction and alcohol-associated liver disease (MetALD) and alcohol-associated liver disease (ALD), where there are currently no approved therapies specifically for these patient populations. MetALD is defined by a steatotic liver together with at least one cardiometabolic risk factor, and in 16 weeks DA-1726 moved all three with statistical significance: liver fat, body weight and HbA1c. MetaVia estimates that 10.7 million U.S. adults have MetALD. DA-1726's dual GLP-1 and glucagon receptor mechanism, its concentration in liver and adipose tissue observed in preclinical studies, and the significant liver fat reduction now demonstrated clinically, provide a strong biological and clinical foundation for this next stage of development. We expect to report full data from Part 3A and Part 3B in the first quarter of 2027 and are planning a 48-week, non-biopsy Phase 2 study in up to 150 subjects with MetALD and ALD, targeted to begin in the second half of 2027."
DA-1726 Part 3B Interim Results
Endpoint, Day 109 (16 weeks)
Baseline, DA-1726 arm
Change from baseline, DA-1726
Placebo-adjusted
p-value vs.
placebo
Liver fat (MRI-PDFF), n=12 vs. 4
5.2 %
All 5 participants with baseline
steatosis (≥5%) fell below 5%
−68% (GMR 0.32)
<0.001
Body weight, n=15 vs. 4
98.6 kg (217 lbs)
−12.19 kg (−26.9 lbs; −11.9%)
−13.5%
<0.001
HbA1c, n=15 vs. 4
5.79 %
−0.44 percentage points (to 5.33%)
−0.24 percentage points
0.006
Waist circumference, n=15 vs. 4
107.5 cm (42.3 in)
−9.6 cm (−3.8 in; −9.0%)
−9.1%
<0.001
DA-1726 64 mg target dose versus placebo. Placebo-adjusted body weight, waist circumference and HbA1c are differences in mean change from baseline versus placebo; liver fat is the geometric mean ratio (GMR) versus placebo in the MRI substudy.
Liver fat: The MRI substudy included 12 DA-1726-treated participants and four placebo participants. Mean baseline liver fat, as measured by MRI-PDFF, was 5.2% in DA-1726-treated participants and 8.0% in the placebo group. At Day 109, DA-1726 achieved a 68% placebo-adjusted reduction in liver fat (GMR 0.32; p<0.001). The absolute MRI-PDFF treatment difference versus placebo was −6.4 percentage points (p=0.007). 10 of 12 DA-1726-treated participants (83%) achieved a relative reduction in liver fat of at least 30%, compared with none of the four placebo participants (p=0.008).
Among the five DA-1726-treated participants with liver steatosis at baseline, defined as MRI-PDFF ≥5%, all five achieved MRI-PDFF below 5% by Day 109. Mean MRI-PDFF in these participants declined from 8.3% at baseline to 3.0% at Day 109, representing a 5.3 percentage-point reduction (p=0.005). The participant with the highest baseline MRI-PDFF experienced a reduction from 12.8% to 4.6%. In comparison, liver fat in the placebo group increased 40.4% from its own baseline.
Glycemic control: Mean baseline HbA1c was 5.79% in the DA-1726 arm and 5.65% in the placebo arm, with all participants in the non-diabetic range at entry. At Day 109, mean HbA1c in the DA-1726 arm fell from 5.79% to 5.33%, a 0.44 percentage-point reduction from baseline (p<0.001), and every DA-1726-treated participant with a Day 109 value showed a reduction of 0.3 to 0.8 percentage points. The placebo arm declined by 0.20 percentage points from its 5.65% baseline. The difference in mean change versus placebo was −0.24 percentage points (95% CI −0.41 to −0.07; p=0.006).
Body composition: MRI-based body composition analysis demonstrated significant reductions across measured adipose tissue compartments. At Day 109, visceral adipose tissue (VAT) was 22% lower versus placebo (GMR 0.78; p<0.001), abdominal subcutaneous adipose tissue (ASAT) was 19% lower versus placebo (GMR 0.81; p=0.002), and total adipose tissue (TAT) was 19% lower versus placebo (GMR 0.81; p<0.001).
Lean tissue and muscle volume were relatively preserved, with thigh muscle volume 9% lower versus placebo (GMR 0.91; p=0.018) and total lean tissue 8% lower versus placebo (GMR 0.92; p=0.007), compared with reductions of 19% to 22% across the measured adipose tissue compartments.
Safety and tolerability: No participant discontinued the study because of a gastrointestinal adverse event, and no new gastrointestinal adverse events were reported after Week 9, or Day 63, through the Day 109 interim assessment. Gastrointestinal adverse events were reported in nine of 15 DA-1726-treated participants, with most events mild to moderate in severity. Vomiting was reported in seven participants (46.7%), nausea in two participants (13.3%), diarrhea in two participants (13.3%), dyspepsia in two participants (13.3%), constipation in one participant (6.7%) and abdominal pain in one participant (6.7%).
One serious adverse event of severe vomiting was reported and considered possibly related to treatment. The participant recovered.
Precision Liver Symposium Presentation Details:
Title: DA-1726, a Dual GLP-1 and Glucagon Receptor Agonist, Leads to Significant Reduction in MRI-PDFF and Weight Loss with Relative Preservation of Lean Mass: A Randomized Placebo-Controlled Trial
Presenting Author: Sarah Browne, M.D., Chief Medical Officer of MetaVia
MetALD KOL Dinner at AASLD's The Liver Meeting 2026
MetaVia will host an invitation-only KOL dinner this evening during the American Association for the Study of Liver Diseases' (AASLD) The Liver Meeting 2026, focusing on MetALD and the evolving treatment landscape.