MetaVia's DA-1726 Demonstrates 9.1% Weight Loss and Significant Metabolic Benefits in Phase 1b Obesity Trial
核心洞察
MetaVia's DA-1726, a dual oxyntomodulin (搜索) analog targeting GLP-1 and glucagon receptors, achieved statistically significant 9.1% weight loss (21.2 lbs) by day 54 in Phase 1b obesity (搜索) trial.
The drug demonstrated additional metabolic benefits including 9.8 cm waist circumference reduction, 12.3 mg/dL fasted glucose improvement, and 23.7% liver stiffness reduction.
No treatment-related discontinuations occurred in the 48 mg cohort, with only mild to moderate gastrointestinal side effects reported.
MetaVia Inc. (搜索) announced positive statistically significant results from its Phase 1b clinical trial of DA-1726, a novel dual oxyntomodulin (搜索) (OXM) analog agonist, demonstrating robust weight loss and comprehensive metabolic improvements in obese patients. The 8-week study of the non-titrated 48 mg dose showed a statistically significant 9.1% weight reduction (21.2 lbs) by day 54, alongside favorable safety and tolerability profiles.
Strong Weight Loss and Metabolic Outcomes
In the multiple ascending dose (MAD) cohort, patients receiving DA-1726 achieved statistically significant weight reduction milestones at multiple timepoints. By day 26, participants experienced an average weight loss of 6.1% (14.6 lbs) with a p-value of 0.003, accompanied by a statistically significant 5.8 cm waist circumference reduction (p=0.006). These improvements deepened through day 54, reaching 9.1% weight loss and a statistically significant 9.8 cm waist circumference reduction (p=0.022).
The drug also demonstrated meaningful glucose control benefits, with patients showing a 12.3 mg/dL improvement in fasted glucose from a baseline of 105.3 mg/dL by day 54. Additionally, one prediabetic subject experienced HbA1c improvement from 6.0% to 5.5% by day 54.
Direct Hepatic Effects Observed
Vibration-controlled transient elastography (VCTE) measurements revealed a 23.7% reduction in liver stiffness from a baseline of 5.9 kPa by day 54. This finding suggests significant direct hepatic effects from DA-1726, which is particularly relevant given that VCTE is recognized by the FDA as a biomarker in MASH (搜索) development.
"Because VCTE is the leading noninvasive tool for liver stiffness assessment and is recognized by the FDA as a biomarker in MASH (搜索) development, seeing a 23.7% reduction in only eight weeks underscores the hepatic potential of DA-1726," said Hyung Heon Kim, president and chief executive officer of MetaVia.
Favorable Safety Profile
The safety profile proved encouraging, with no treatment-related discontinuations in the 48 mg cohort. Gastrointestinal events were mild to moderate in severity, representing a significant tolerability advantage compared to existing therapies in the obesity (搜索) space.
Mechanism and Competitive Positioning
DA-1726 functions as a dual agonist of GLP-1 receptors (GLP1R (搜索)) and glucagon receptors (GCGR), leading to weight loss through both reduced appetite and increased energy expenditure. Kim emphasized the potential competitive advantages: "We believe the statistically significant waist reductions reflect the glucagon component of DA-1726, which may contribute to deeper visceral fat loss than GLP-1 agonists alone."
The company highlighted that DA-1726 has demonstrated glucose lowering without elevations, which may offer both clinical and reimbursement advantages. This is particularly significant given that 70% to 80% of people with obesity (搜索) have diabetes (搜索) or prediabetes (搜索), and diabetic patients typically receive broader insurance coverage for anti-obesity therapies.
Clinical Trial Design and Future Plans
The Phase 1 trial was a randomized, double-blind, placebo-controlled study evaluating safety, tolerability, pharmacokinetics, and pharmacodynamics of DA-1726 in obese but otherwise healthy adults with BMI of 30-45 kg/m². Nine subjects in each cohort were randomized in a 6:3 ratio, receiving either 4 weekly administrations of DA-1726 or placebo, with the extended dosing cohort receiving 8 weeks of exposure.
MetaVia plans 16-week titration studies, including a 48 mg single-step titration and a 64 mg two-step regimen, with results expected in the fourth quarter of 2026. Kim expressed confidence in the drug's competitive positioning: "Our planned 16-week titration studies reflect our confidence in DA-1726's tolerability and our expectation that it will compare favorably to the slower, more restrictive titration schedules required by today's GLP-1 drugs."
Market Context
The positive results come during a rapidly evolving obesity (搜索) treatment landscape. The global obesity market across seven major markets is predicted to reach $173.5 billion by 2031, with weight loss drugs expected to continue being a major industry trend, particularly in North America.