MetaVia Inc. has announced positive top-line results from the 4-week multiple ascending dose (MAD) portion of its Phase 1 clinical trial evaluating DA-1726, a novel dual receptor agonist for obesity treatment. The drug demonstrated significant weight loss and favorable safety outcomes, positioning it as a potential competitor in the rapidly expanding weight loss medication market.
In the 28-day study involving 36 subjects, DA-1726 showed compelling efficacy at the 32 mg dose level without requiring dose titration. Participants achieved a maximum weight reduction of 6.3% and a mean weight loss of 4.3% from baseline by day 26 (p=0.0005). Notably, no plateau effect was observed during the relatively short treatment period.
Dual Mechanism Drives Efficacy and Tolerability
DA-1726 represents a novel approach to obesity treatment as an oxyntomodulin (OXM) analog that functions as both a glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) dual agonist with a 3:1 ratio. This balanced activation appears to provide complementary metabolic benefits.
"The Phase 1 MAD data underscore DA-1726's potential as a best-in-class obesity drug demonstrating compelling safety, tolerability and strong weight loss effects," stated Hyung Heon Kim, President and Chief Executive Officer of MetaVia. "Given GLP-1R lowers glucose levels while GCGR increases them, the 3:1 ratio of DA-1726 may provide an optimal balance to achieve a sustainable and tolerable therapeutic effect in this class of drugs."
The dual mechanism also produced significant reductions in waist circumference, with a maximum decrease of 3.9 inches and a mean reduction of 1.6 inches by day 33. Importantly, these effects were partially sustained, with a 1.46-inch reduction persisting nearly a month after the final dose.
Favorable Safety and Tolerability Profile
A key finding from the trial was DA-1726's promising safety profile. Only 25% of subjects receiving the drug experienced gastrointestinal adverse events, which were predominantly mild and transient, typically resolving within 1-3 days. At the 32 mg dose level, four of six participants reported mild GI events that generally resolved within 24 hours.
The specific adverse event rates included nausea (12.5% vs. 8.3% on placebo), vomiting (16.7% vs. 8.3% on placebo), and constipation (12.5%). No treatment-related discontinuations or serious adverse events occurred during the study.
This tolerability profile could represent a significant advantage over existing GLP-1 agonists, which often face adherence challenges due to side effects. According to MetaVia, 20-30% of patients on current GLP-1 medications discontinue treatment within the first month, and up to 70% stop within a year.
Metabolic Benefits Beyond Weight Loss
Beyond weight reduction, DA-1726 demonstrated meaningful effects on glucose metabolism, with a maximum lowering of fasting glucose by 18 mg/dL and a mean reduction of 5.3 mg/dL at day 26. This occurred despite the drug's glucagon agonism, which typically raises blood glucose.
"Despite DA-1726's glucagon agonism, fasting plasma glucose was well controlled and showed reduction without any hypoglycemic adverse events in all cohorts," noted Kim. "The pharmacokinetic results demonstrated a favorable exposure profile and dose proportionality to support the proposed weekly dosing of DA-1726."
Early satiety was observed in 83% of patients receiving the 32 mg dose, suggesting an appetite-suppressing effect that could contribute to weight loss in longer-term studies.
Expanding Development Plans
Based on these promising results, MetaVia is expanding its development program for DA-1726. The company plans to add higher-dose cohorts to the Phase 1 study to determine the maximum tolerated dose, which has not yet been reached.
Additionally, MetaVia is planning a Phase 1 Part 3 study that will specifically target patients who discontinued Wegovy (semaglutide) treatment early. This trial aims to demonstrate DA-1726's potential superiority in tolerability and safety while maintaining effective weight loss.
"Our goal is to develop an obesity drug that can be used safely in all obese patients with different comorbidities," Kim explained. The company believes DA-1726's dual mechanism could benefit patients with obesity-related conditions such as type 2 diabetes and Metabolic Dysfunction-Associated Steatohepatitis (MASH).
Trial Design and Methodology
The Phase 1 trial was designed as a randomized, double-blind, placebo-controlled study evaluating single and multiple ascending doses of DA-1726. The MAD portion enrolled healthy adults with BMI between 30-45 kg/m².
Primary endpoints focused on safety and tolerability through monitoring adverse events. Secondary endpoints included pharmacokinetics, while exploratory measures examined effects on metabolic parameters, cardiac function, lipid levels, body weight, waist circumference, and BMI.
Preclinical studies had previously shown that DA-1726 produced greater weight loss than semaglutide (Wegovy) and similar weight reduction to tirzepatide (Zepbound) despite higher food consumption. The compound also preserved lean body mass and demonstrated superior lipid-lowering effects compared to survodutide, another dual agonist.
DA-1726 is administered as a once-weekly subcutaneous injection, consistent with the dosing schedule of currently approved GLP-1 receptor agonists for obesity treatment.
