MetaVia has announced positive results from the four-week multiple ascending dose (MAD) Part 2 of its Phase I clinical trial of DA-1726 for the treatment of obesity. 

DA-1726 is a novel, dual oxyntomodulin (OXM) analog agonist that functions as a glucagon-like peptide-1 receptor (GLP1R) and glucagon receptor (GCGR).

In the 28-day, 36-subject MAD portion of the study, DA-1726 demonstrated excellent safety and tolerability, with positive clinical activity.  

The cohort receiving 32mg of DA-1726 with no titration demonstrated a maximum reduction in body weight from baseline ranging up to -6.3%, and a mean body weight reduction of -4.3% at Day 26.  

Four out of six subjects on the 32mg dose experienced mild gastrointestinal (GI) adverse events (AEs), most of which were resolved after 24 hours of occurrence. There were no treatment-related discontinuations or serious adverse events (SAEs). 

“The Phase I 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. “Although subjects in this study were exposed to study drug or placebo for a total of 26 days, no signs of plateau were observed. 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. 

“Early satiety was observed in 83% of patients on the 32mg dose, which we believe may be suggestive of efficacy and we anticipate that greater weight loss may be seen in longer duration studies. Not all obese patients need to lose 30% of their weight and it is our goal to develop an obesity drug that can be used safely in all obese patients with different comorbidities.” 

Potential best in class obesity drug

With the mean baseline of 41 inches, DA-1726 showed a waist circumference reduction of 1.6 inches on average, with a maximum reduction of 3.9 inches by day 33. 

Further, DA-1726 demonstrated potentially best-in-class lowering of fasted glucose of -5.3mg/dL and a maximum of -18mg/dL at Day 26, allowing for a potential expansion into type 2 diabetes and obese MASH patients.  

Mr Kim continued: “It is well known that many patients on current GLP-1 agonists discontinue treatment due to tolerability issues, with 20% to 30% stopping within the first month and up to 70% within a year. With DA-1726’s balanced activation of GLP1R and glucagon receptors enhancing energy expenditure, we remain confident in its potential to become a best-in-class obesity drug, with the further potential to offer superior tolerability than currently marketed GLP-1 agonists and those in late-stage clinical trials.” 

The company plans to conduct a Phase I Part 3 study which will investigate DA-1726 on Wegovy early drop-out patients. One or more additional cohorts with a higher dose will also be added to the Phase I study in order to further explore the maximum tolerated dose.

Diana Spencer, Senior Digital Content Editor, DDW