Zealand's GLP-1/GLP-2 agonist shows minimal weight reduction at low doses

Zealand Pharma recently emphasized that much higher doses of their drug dapiglutide are currently under investigation in an ongoing 13-week Phase 1b trial. The company's GLP-1/GLP-2 receptor dual agonist showed modest results in a recent study when administered in low doses, but the Danish firm believes higher doses will demonstrate the drug's true potential.

In a 54-person Phase 2 trial, participants were administered either a 4-mg or 6-mg weekly subcutaneous dose of dapiglutide or a placebo over 12 weeks. The results showed that those who received the 4-mg dose experienced an average weight loss of 2.9%, which was only marginally better than the 2.2% weight loss observed in the placebo group. The 6-mg dose group achieved a slightly higher weight loss of 4.3%. Notably, no lifestyle interventions were included in the trial.

When examining the statistical significance, both doses failed to achieve noteworthy results. The 4-mg dose had a p-value of 0.483, and the 6-mg dose had a p-value of 0.077, indicating that these doses are at the lower end of the therapeutic range, according to Zealand.

Despite the unremarkable data, Zealand Pharma highlighted the ongoing investigation into much higher doses of dapiglutide in their 13-week Phase 1b trial, which is expected to yield top-line results in the latter half of the year.

Zealand's Chief Medical Officer, David Kendall, M.D., expressed optimism in a May 23 release, stating, "We are encouraged by the reductions in body weight observed in this investigator-led mechanistic trial using low doses of dapiglutide. Our ongoing 13-week phase 1b dose-titration trial is currently evaluating higher doses of dapiglutide up to 13 mg, and based on the tolerability profile observed to date, we will seek to investigate even higher doses going forward." The company is banking on achieving better efficacy with these increased doses.

However, investors reacted negatively, leading to a more than 3% decline in Zealand Pharma's shares during early morning trading in Europe.

The company reported that the number of treatment-emergent adverse events was lower than those reported in studies of other incretin-based therapies, with most adverse events being gastrointestinal-related. Importantly, none of these events led to patients discontinuing their treatment.

Despite the inconclusive results from the recent trial, investor focus seems to have shifted to other promising developments within Zealand's pipeline. Analysts at Jefferies recently identified an upcoming Phase 1b weight loss readout for the company's long-acting amylin petrelintide as a major catalyst to watch. Additionally, Zealand's survodutide, developed in partnership with Boehringer Ingelheim, demonstrated its potential to treat metabolic dysfunction-associated steatohepatitis in a Phase 2 trial earlier this year. In this context, dapiglutide received only a brief mention in the analysts' report.

In summary, while the initial low-dose trials of dapiglutide did not meet expectations, Zealand Pharma remains optimistic about the potential of higher doses currently under investigation. The biotech firm is committed to continuing its research and believes the higher doses will ultimately demonstrate the drug’s efficacy and value.